General considerations

There are currently a wide variety of products available for soft tissue grafting and wound treatment. These products differ in species source (e.g., human cadaveric, synthetic, bovine, porcine, equine, a combination of several types, etc.), tissue source (e.g., dermis, pericardium, intestinal mucosa, etc.), bioburden reduction (e.g., nonsterile, sterile), additives (e.g., antibiotics, surfactants), delivery formats (e.g., wet packaged, freeze-dried), and preparation requirements (e.g., multiple rinses, rehydration). Additionally, they are procured, produced, manufactured, or processed in sufficiently different manners that they cannot be addressed and evaluated as equivalent products. This is made evident not only in the wide range of shelf-life recommendations for these types of products, but also in the descriptions of their physical properties. Additionally, there are a limited number of comparative studies available addressing the clinical outcomes for allographic, xenographic, and composite products, and the results are heterogeneous. What comparative data is available demonstrates a wide range of outcomes, with some studies reporting no differences and others indicating significant differences in the rate of healing, incidence of seroma and infection, surgical failure, and other outcomes. Therefore, each product is assessed on the basis of the available scientific evidence specific to that product rather than considering groups of products as belonging to a class (for example, acellular dermal matrix products) and then evaluating all members of that class as though they were therapeutically equivalent. While this approach has certain merits, within each possible class that could be constructed there are products that have no full-text, peer-reviewed, published studies available to evaluate the clinical utility or draw a conclusion as to whether that particular product is therapeutically equivalent to another similar but studied product. Products for which there is a lack of quality published and peer-reviewed evidence to consider are considered investigational and not medically necessary. For other products, there may be one or more published studies of varying quality. The use of blinding in studies for these types of products may pose a challenge due to the nature of the products compared to standard therapies, as well as other factors. However, investigators should strive to design and apply rigorous study methodologies to minimize possible sources of bias within their trials.

Below, findings of recent or notable studies published in peer-reviewed medical literature are summarized for each product. The literature discussed and included in this document should not be construed to represent all of the scientific evidence available on a topic or reviewed in document development.

Non-Product Specific Acellular Dermal Matrix (ADM) Studies, Multiple Product Studies, Meta-analyses, and Systematic Reviews

The use of ADM products of various origins has been proposed for both immediate and two-stage breast reconstruction surgeries and has become widely used and accepted. However, the current evidence of these techniques has been understudied and the data that has been made available is not from rigorously designed and conducted randomized controlled trials (RCTs).

To properly address the question of both safety and efficacy, the MultiCentre Canadian Acellular Dermal Matrix trial (MCCAT) has begun recruitment in a two-arm parallel superiority trial that will compare one-stage ADM facilitated implant breast reconstruction with two-stage tissue expander and implant breast reconstruction (Zhong, 2013). The results addressing this pressing issue are eagerly anticipated.

In 2012, two well-designed meta-analysis studies were published that evaluated the available peer-reviewed published evidence addressing the use of ADMs for use in breast reconstruction procedures. Ho and colleagues conducted their meta-analysis using 16 studies that met their inclusion criteria. They noted that analysis of complication rates was limited by the small number of studies and the small sample size of study participants. Additionally, they commented that the overall quality of the evidence was low. Five studies were included that had data for both participants who received ADM and those who did not. Overall, they found that the ADM group had significantly higher complication rates for seroma, infection, and reconstructive failure when compared with the non-ADM group. ADM-assisted breast reconstructions were found to be almost 4 times as likely to be complicated by seroma, nearly 3 times as likely to become infected, and 3 times as likely to have a reconstructive failure as breast reconstructions performed without the use of ADM. After exclusion of outlier data, they found that the pooled odds ratio (OR) of developing skin flap necrosis in ADM reconstructions was three-fold higher than non-ADM reconstructions.

Kim and others conducted a meta-analysis on 44 studies that met their inclusion criteria. The results found that there was an increased rate of total complications with ADM use when compared to non-ADM reconstructions (15.4% vs. 14.0%). For specific complications, this finding continued to apply; specifically for seroma (4.8% vs. 3.5%), infections (5.3% vs. 4.7%), and flap necrosis (6.9% vs. 4.9%). However, the rate of hematoma was greater in the control cohort (1.5% vs. 1.0%). The rate of reconstructive failure was very similar in both cohorts, 3.8% vs. 3.8%. When looking at the studies that provided comparative data between ADM and non-ADM groups in the same study, the authors noted that there was an increase in the risk of total complications (relative risk [RR], 2.05; 95% confidence interval [CI], 1.55 to 2.70), seroma (RR, 2.73; 95% CI, 1.67 to 4.46), infection (RR, 2.47; 95% CI, 1.71 to 3.57), and reconstructive failure (RR, 2.80; 95% CI, 1.76 to 4.45) in the ADM group vs. the non-ADM group. These findings call into question the practice of using ADM for breast reconstruction surgery.

A systematic review of ADM use for abdominal wall reconstruction was published by Zhong and others (2011). They report on a total of 30 articles that met inclusion criteria, specifically mentioning that they did not identify any level I or II studies addressing this issue. They included 4 level III and 26 level IV studies. Among their findings they report wide variation in indications for ADM use and poorly defined terminology used to define participant populations (e.g., abdominal wall reconstruction, high-risk/recurrent/complex/large ventral hernia and high-risk/contaminated wound). The incidence of postoperative hernia varied widely, with some studies reporting 0% and others reporting 80%. Out of the 30 studies reviewed, three used porcine ADM, one a synthetic composite mesh, and one a bovine-derived ADM. No separate data was provided for these studies. The remainder of the studies used allogeneic ADMs. Within the literature, there was significant variation with regard to placement of ADMs within the surgical field, with ADM used as underlay/inlay, interposition, overlay/onlay or sandwiched (underlay and overlay) repairs. The type of fascial repair (bridged vs. reinforced) also had significant impact on outcomes. They state that in cases where fascial re-approximation was achieved, ADM used in a reinforced repair with fascial re-approximation was significantly better than that used in a bridged repair without fascial re-approximation. With the significant variation in selection criteria, ADM types, and surgical techniques, this pool of evidence should not be used to evaluate the use of ADM for abdominal reconstructions in a global manner, and each study should be weighed on its own merits.

Ibrahim and colleagues (2013) conducted a large retrospective study using data from the American College of Surgeon’s (ACS) National Surgical Quality Improvement Program (NSQP) database. The study investigated 30-day outcomes in 19,100 cases that involved tissue expander implant-based breast reconstruction surgeries. A subset of 3301 (17.3%) cases involved the use of ADMs as part of the surgical procedure. It was reported that, overall, the rate of complications was not statistically different between cases that used ADMs (n=175, 5.3%) and those that did not (n=776, 4.9%) (p=0.396). This rate is much lower than the rate of complications reported in previous studies. It should be noted that there are several major limitations of this study, including the fact that the data was derived retrospectively from a large database with no randomization, no blinding, and no concurrent comparison groups. Additionally, the ACS does not use a standardized definition for the term “complications.” This presents a major problem, considering that there may be significant heterogeneity in the major study endpoint data. Also of import is that the data in the NQSP database is derived from academic medical centers, and no data from community hospitals and private clinics is included. It is unclear whether or not this had an impact on complication rates. Finally, there were significant differences between groups at baseline with regard to age, race, and type of reconstruction, which may have introduced significant bias into the analysis.

In 2017, Lee and others published a meta-analysis investigating the use of ADMs for implant-based breast reconstruction. A total of 17 studies were included, with only one being a prospective RCT and the others having retrospective nonrandomized designs. There were 12 studies available involving comparisons with FlexHD, DermaMatrix, and aseptic or sterile AlloDerm products. In the meta-analysis comparing FlexHD and aseptic AlloDerm, involving a total of six studies, both products showed similar pooled risks for all complications. For comparisons between DermaMatrix and aseptic AlloDerm, the results from four studies likewise found no differences between the pooled risks of complications. Finally, the meta-analysis of four studies comparing the aseptic or sterile forms of AlloDerm demonstrated that the pooled risks for the complications did not differ. The authors concluded that these products have similar risks of complications.

Sorkin (2017) reported the results of a retrospective controlled study involving 1297 participants who underwent expander/implant-based breast reconstruction procedures with either ADM (n=655) or no ADM (n=642). At 2 years post-procedure, no significant differences were seen between groups with regard to overall complications (OR, 1.21; p=0.263), major complications (OR, 1.43; p=0.052), wound infections (OR, 1.49; p=0.118), or reconstructive failures (OR, 1.55; p=0.089). No significant differences were reported in participant-reported outcome scores, including satisfaction with breasts, psychosocial well-being, sexual well-being, physical well-being, and postoperative pain.

Schnarrs (2016) reported the results of a retrospective non-randomized controlled trial involving 126 participants who underwent 170 breast reconstruction procedures involving the use of aseptic AlloDerm (n=143), sterile AlloDerm (n=19), FlexHD (n=18), and hMatrix (n=32). The authors reported no significant differences between groups with regard to complication rates (p>0.05). They also reported that both smokers and large-breasted participants (≥ 500 g) were at significantly higher risk for complications vs. nonsmokers and non-obese participants (p<0.01 and p<0.03, respectively). The conclusion was that there were no significant differences between products with regard to complications. However, the study design, including disparate group sizes, limits the generalizability of these findings. Results from more rigorously designed and conducted trials would be helpful in better understanding the comparability of various soft tissue grafting products used in breast reconstruction procedures.

Samules (2023) conducted a meta-analysis investigating the efficacy of ADMs for the treatment of capsular contracture, a common complication of breast augmentation procedures. The analysis included 9 total studies, all retrospective, with a total study population included 481 breasts. The ADMs included in the study were AlloDerm, DermaMatrix, FlexHD, NeoForm, Strattice, and SurgiMend, representing 11.5%, 0.4%, 3.8%, 0.81%, and 79.1%, of the breasts treated, respectfully. In the pooled data, a significant difference between products was noted with regard to the incidence of recontracture (p<0.01). Both NeoForm and SurgiMend had a 25% contracture rate, and AlloDerm, DermaMatrix, and FlexHD groups had no contractures reported. Similarly, a significant difference between groups was reported with regard to complication rates (p<0.01), with NeoForm having a 50% complication rate and SurgiMend a 12.5% rate. The pooled complications rates for AlloDerm, DermaMatrix, and FlexHD were 1.75%, 0.0%, and 5.26%, respectively. This study demonstrates significant variability in both outcomes and safety between different ADM products, highlighting the importance of consideration of such products as individuals and not as a class

Clark (2024) reported the results of a meta-analysis of synthetic mesh products used in breast reconstruction procedures. The pooled analysis included a total of 27 studies, 8 comparative and 19 noncomparative. The comparative trials involved ADM comparator groups. In the comparative trials, the synthetic products used were Phasix, Seragyn, TIGR, Ti Loop. The ADM comparators included AlloMax, Protexa, Surgisys, Strattice, and Veritas. Additional unspecified products of both types were included in one study. In the noncomparative trials, the products used were Seragyn, TIGR, Ti Loop, ULTRAPRO and Vicryl Mesh. The authors reported significant heterogeneity in complication and explantation rates (I²=69%-74%), necessitating the use of a random effects model. In the comparative studies, no significant differences were reported between the synthetic and ADM groups with regard to the risk of infection (RR, 0.53, 95% CI [0.26-1.10]). Conversely, the risk of major complications was significantly higher in the ADM mesh group (RR, 0.54, 95% CI [0.33-0.89]). The risk of explantation was also found to be significantly higher in ADM mesh (RR, 0.43, 95% CI [0.21-0.87]). In the non-comparative studies, significant heterogeneity was demonstrated with regard to reported rates of seroma, infection, major complication, and explantation (I² = 52%-89%). The rates of seroma ranged from 0% to 26%, yielding a meta-rate of 3% and 95% CI (1%-6%). The rates of infection ranged from 0% to 16% yielding a meta-rate of 4% and 95% CI (3%-6%). Major complication ranged from 1% to 26% yielding a meta-rate of 10% and 95% CI (7%-13%). Explantation rate ranged from 0% to 11% yielding a meta-rate of 3% and 95% CI (2%-5%). The studies with lower larger cohorts generally reported higher rates of complication, which may indicate small-study bias and reflect inappropriately low complication rates. The authors concluded that the data demonstrated noninferiority of synthetic products in all outcomes assessed. Furthermore, they stated that the noncomparative studies of synthetic products demonstrated similar rates of seroma, infection, reoperation, and explantation to those published for ADM mesh. The results of this trial support the premise of product equivalency.

Contradictory results were reported by Hu (2024), who reported the results of a meta-analysis involving 32 studies evaluating the use of synthetic or ADM products for breast reconstruction. Six of the studies included were RCTs and 26 were cohort studies. ADM products included in the analysis were AlloDerm, AlloMax, Strattice, and Surgisis. The synthetic products included were TCPM, TIGR, TiLoop, and Vicryl Mesh. AlloDerm and TiLoop were the most commonly used products. In the analysis of ADM products to no mesh, infection rates were 2.12 times more likely to occur with ADM products (RR, 2.12, 95% CI 1.60–2.80). Additionally, implant loss was 2.14 times more likely with ADM products compared to no mesh (RR, 2.14, 95% CI 1.30–3.52). Similarly, the risk of nipple areola and flap necrosis was 1.65 times higher in the ADM group compared to no mesh (RR, 1.65, 95% CI 1.27–2.14). In the analysis comparing outcomes with and without synthetic products, the occurrence of complications (including infection, nipple areola and flap necrosis, implant loss, capsular contracture, hematoma, and seroma), none of the results were meaningful. In the analysis comparing ADM to synthetic products, the overall complication rate was 2.07 times higher in the ADM group compared to the synthetic group (RR, 2.07, 95% CI 1.14–3.78). The risk of seroma was 4.50 times higher in the ADM group compared to the synthetic group (RR, 4.50, 95% CI 2.27–8.95). Use of the Egger test showed no potential publication bias (p=0.179). These findings not only illustrate significant differences in outcomes between products, but also demonstrate significant risks to the use of mesh products overall in breast reconstruction procedures.

Silverstein (2024) conducted a retrospective analysis of 39 participants (78 breasts) who underwent hybrid breast reconstruction over an average follow-up of 50.4 months. Postoperative complications included hematoma (2.6%), mastectomy skin necrosis (15.4%), and fat necrosis (7.7%), with no instances of implant infection, exposure, or flap failure. Polyglactin mesh was used in 24 breasts and ADM in 54 breasts. The polyglactin group experienced higher rates of implant malposition and capsular contracture, leading to 41.7% requiring implant replacement compared to 1.9% in the ADM group (p<0.001). Multivariable regression revealed that polyglactin mesh increased the probability of needing implant replacement by 36 times compared to ADM (p=0.006). The study concluded that ADM is associated with lower rates of capsular contracture and implant malposition than polyglactin mesh in hybrid breast reconstruction.

Murphy (2023) reported the results of a meta-analysis of studies that involved direct comparison of ADM or synthetic mesh products or to another technique as part of implant-based breast reconstruction procedures. The analysis included a total of 31 articles, with a subgroup analysis of 13 studies involving single-stage direct-to-implant procedures. The final pooled data included 12,898 participants stratified across four different surgical strategies, including use of human ADM (HADM), xenograft ADM (XADM), synthetic mesh, and no use of ADM or mesh. The most commonly investigated product was AlloDerm, followed by Strattice, and SurgiMend. Complete data regarding the products included in the study was not provided. Implant loss was included as a reported endpoint in 29 studies involving 13,257 procedures, with a total of 696 implant loss events. Six pairwise comparative studies were excluded from the network meta-analysis because no event occurred in either arm. In comparisons of all strategies with HADM, none were found to be superior with regards to implant loss. No product was ranked as the best treatment modality to reduce odds of implant loss. Thirty studies included direct comparisons of the four strategies, involving 12,433 procedures. A total of 2366 complications were reported. The most frequent reported comparison was HADM compared to no ADM or mesh. The authors reported that the use of XADM, synthetic mesh, and no ADM or mesh all reduced the odds of complication compared with HADM. However, only no ADM or mesh significantly reduced the odds of overall complication occurrence compared with the use of HADM (OR, 0.54; 95% CI, 0.39, 0.73). Multiple comparisons found that use of no ADM or mesh was the best treatment strategy to reduce the odds of overall complication rates, with the odds of overall complications when no ADM or mesh was used compared HADM being 0.53 (95% CI, 0.39, 0.73). Interestingly, no significant difference between no ADM or mesh and synthetic mesh were reported with regard to complications (OR, 0.82; 95% CI, 0.46, 1.47), Similarly, when no ADM or mesh was compared to XADM the odds of overall complications was 0.68 (95% CI, 0.44, 1.06). In comparisons of HDAM to and XADM, there was a significant reduction in the odds of overall complication in favor of XADM use (OR, 0.45; 95% CI, 0.23, 0.86). The incidence and odds of surgical site infection was assessed in 28 of the included studies, with 3 studies reporting significant results in regard to odds of infection occurring. HADM had the highest odds of developing surgical site infection. When compared to HADM, XADM (OR, 0.60; 95% CI, 0.38, 0.93) and no ADM or mesh (OR, 0.67; 95%: CI, 0.49, 0.29) demonstrated significant reductions in the odds of surgical site infection occurring. Overall, they reported that XADM was ranked as the best strategy to reduce odds of postoperative surgical site infection when compared to ADM. Seroma occurrence was assessed in 27 studies. Use of no ADM or mesh was found to be the best treatment to option to decrease the odds of seroma formation. Use of no ADM or mesh was reported to significantly decrease the odds of developing seroma compared to HADM (OR, 0.52; 95% CI, 0.29, 0.95). Regarding the odds of flap necrosis, the authors noted that synthetic mesh was found to be the treatment with the lowest incidence of flap necrosis complications. Compared to XADM, the use of no ADM or mesh demonstrated a significantly decreased rate of flap necrosis (OR, 0.13; 95% CI, 0.02, 0.91). Capsular contraction rates were reported in 7 studies with postmastectomy radiotherapy. When comparing all strategies to HADM, a trend favoring HADM in decreasing capsular contraction is evident, but none of the comparisons reported reached significance. The authors reported that in multi-treatment comparisons using direct and indirect evidence, HADM was the best treatment. Statistically, there was considerable heterogeneity among the ORs with broad CIs, thus they concluded that no treatment could confidently be considered superior for reducing capsular contraction. Additionally, the results were associated with wide CIs, suggesting heterogeneity of the data and limited sample size. This study further emphasizes significant differences in soft tissue grafting products for breast reconstruction, and questions their use in light of the data demonstrating high complication rates for some types of products. The question remains if these complications rates are related to specific products or can be generalized to a class of product types.

In a systematic review and meta-analysis covering thirty studies and forty cohorts (involving 1,369 individuals) with burns exceeding fifty percent of the total body surface area, Haug (2024) analyzed autografting, allografting, cultured epidermal autografts, and Meek micrografting. Even though NovoSorb BTM, AlloDerm, PolarityTE, ReCell, and SkinTE were part of the initial search criteria, those products were not individually evaluated for quantitative outcomes, so the final comparisons centered on these four main techniques. The investigators measured mortality, graft take, hospital length of stay, and number of operations. Autografting showed the highest overall mortality (50%), yet provided the most robust graft adherence, which approached 95% in the pooled results. Cultured epidermal autografts had the lowest mortality rate (approximately 10%), a difference that was statistically significant when compared with autografting (p=0.001) and allografting (p<0.001). Individuals who underwent Meek micrografting experienced the shortest average hospital stay, roughly fifty days, and required fewer total operations than those treated with the other options. Allografting, while less favorable on some metrics, was associated with shorter inpatient stays than cultured epidermal autografts (p=0.02). The authors concluded that cultured epidermal autografts may offer a survival advantage, Meek micrografting could reduce operative burden and time in the hospital, and autografting provided the strongest graft take. They emphasized, however, that considerable variability among the studies, along with limited long-term outcome data, warrants further prospective research to determine optimal standards of care for extensive burn injuries. This study demonstrates variable outcomes based on the procedure and products used in the treatment of burns, supporting the need for individual product-level evaluations of clinical utility.

Chen (2024) conducted a systematic review and network meta-analysis involving 38 randomized controlled trials and 3,862 individuals with diabetic foot ulcers, comparing various biomaterials and topical treatments to standard therapy. Among these trials, Hyalograft 3D achieved a 24% complete wound closure rate at 12 weeks compared to 21% with standard therapy (p~0.03). SkinTE reached 72% complete wound closure at 12 weeks compared to 32% with standard therapy (p<0.001). AlloPatch Pliable yielded an 80% complete wound closure rate at 12 weeks versus 30% for standard therapy (p<0.001). Overall, these findings highlight that certain biomaterials can outperform conventional dressings in facilitating complete ulcer closure and demonstrates variable outcomes based on products used in the treatment of DFUs.

A systematic review and meta-analysis by van den Bosch (2024) assessed the effectiveness of dermal substitutes for acute burns requiring scar reconstruction including 31 moderate-quality trials. The study found that using a collagen-elastin matrix resulted in delayed re-epithelialization 4–7 days after treatment compared to split-thickness skin graft in acute burns (-7.30%, p=0.02). However, it improved scar quality six months post-operation (-1.95, p<0.01). There was a notable difference between Matriderm and Integra regarding scar contraction rates. In the sub-analysis regarding healing time, on average, wounds took 5 days longer to close in the ADM group. The authors concluded that the use of dermal substitutes in burns and the reconstruction of burn scars may offer benefits in enhancing scar quality. Limitations of the analysis included study design variability and small sample sizes.

Product Specific Evidence

Ac5 advanced wound system

AC5 Advanced Wound System (Arch Therapeutics, Inc., Framingham, MA) is a synthetic, self-assembling peptide-based wound matrix cleared by the FDA through the FDA 510(k) process for use in partial- and full-thickness wounds. In a prospective, single-arm study by Treadwell (2024), 15 individuals (6 men, 9 women; ages 25 to 80) with challenging acute or chronic wounds were recruited. Their wounds had a mean duration of 21 months (the oldest at 7 years) and a mean surface area of 9.5 cm² (the largest at 32 cm²). Eleven individuals received weekly AC5 applications, and four received AC5 treatment every other week, for up to 8 weeks. Among the weekly group, 64% achieved more than 50% wound area reduction at 4 weeks, and 73% had more than 60% reduction at 8 weeks. In the every-other-week group, 25% reached 50% reduction by 4 weeks, and 50% by 8 weeks. No adverse events were reported. The authors reported that AC5 easily conformed to uneven wound geometry, including tunneled or undermined wounds. They concluded that weekly application of AC5 appeared more most effective compared to biweekly application. Additional, larger studies are warranted to determine optimal application frequency.

Aesten Inject (see MegaDerm)

Affinity

Affinity is a cryopreserved human amnion-derived tissue allograft and is treated as human tissue for transplantation under the FDA’s HCT/P process. There is currently only one available study published on its use in human participants.

Serena (2020) reported on the results of an unblinded prospective RCT involving 76 participants with DFUs treated with either Affinity plus standard care (n=38) or standard care alone (n=38). Wound closure for the Affinity group was significantly greater than the control group at both 12 weeks (55% vs. 29%, p=0.02) and 16 weeks (58% vs 29%, p=0.01). At 16 weeks, wound closure was reported in 60% of Affinity participants vs. 48% of control participants (p=0.04). The authors reported that the probability of wound closure with Affinity vs. standard care increased by 75% (HR, 1.75). The authors concluded that the use of Affinity increased the frequency and probability of DFU wound closure. Additional data from well-designed trials are warranted to support these conclusions.

AlloMax

AlloMax is an acellular, non-cross-linked allograft dermis product and is treated as human tissue for transplantation under the FDA’s HCT/P process. The currently available evidence in the peer-reviewed published literature addressing the use of AlloMax is sparse. A case series study involving 65 participants undergoing tissue expander breast reconstruction was described by Venturi (2013). The results of this study are limited but include a complication rate of 4.6% (3 participants). These included one case of cellulitis and two cases of partial mastectomy flap necrosis requiring debridement. No seromas or explantations were reported. Histological verification of full graft incorporation was demonstrated in the first 20 biopsies. A second retrospective case series involving 203 participants (348 breasts) undergoing mastectomy with immediate breast reconstruction was reported by Rundell in 2014. The authors reported that infection occurred in 6.6% of participants, with 3.7% being major infections requiring intravenous antibiotics and 2.9% being minor infections requiring oral antibiotics only. Seromas occurred in 3.4% of cases and reconstruction failure occurred in 0.6% of cases. The authors stated that the analysis suggested that the complication prevalence was significantly higher in individuals with a BMI > 30 (p=0.03).

AlloPatch

AlloPatch is a product composed of acellular human dermis treated as human tissue for transplantation under the FDA’s HCT/P process.

At this time, there is limited evidence published in the peer-reviewed literature addressing the use of this product. The most rigorous study to date involved 45 participants with chronic refractory DFUs (Zelen, 2016b). A total of 40 participants in this investigator blinded RCT were assigned in a 1:1 fashion to either standard care alone (n=20) or AlloPatch plus standard care (n=20). AlloPatch grafts were applied weekly for up to 12 weeks. Initial ulcer size at baseline was greater in the AlloPatch group vs, controls (4.7 cm² vs. 2.7 cm²). At 6 weeks, the authors reported that 65% of the AlloPatch group participants were completely healed (13/20) vs. 5% in the control group (1/20). At 12 weeks, the proportions of DFUs healed were 80% and 20%, respectively. The mean time to heal within 12 weeks was 40 days in the AlloPatch group vs. 77 days for controls. No differences between groups were reported with regard to adverse or serious adverse events. The authors reported that, “Weekly application of HR-ADM is an effective intervention for promoting closure of non-healing DFUs.”

This group published a continuation study with an additional 40 participants (n=20 per group) and results of the total 80 participant population were reported by Zelen in 2018. In the continuation population, the AlloPatch group had more smokers (7 vs. 1, p=0.044) and the control group was older (67 years vs. 55 years, p=0.008). At 6 weeks, 85% of the AlloPatch group vs. 15% of the controls were completely healed (p=2.7 x 10^-6). The mean PAR in wounds was greater in the AlloPatch group (62% vs. 50%, p=2.7 x 10^-6). Mean time to healing at the 6-week time point was 27 days for the AlloPatch group vs. 41 days for controls (p=9.9 x 10^-7). At 6 weeks, 2 AlloPatch participants (5%) and 19 control participants (48%) were withdrawn from the study due to failure to have a 50% reduction in wound area. At 12 weeks, 80% of AlloPatch participants and 30% of the control participants had complete wound healing (p=8.4 X 10^-6). At 12 weeks, mean time to heal was 38 days in the AlloPatch group vs. 72 days in the control group (p=3.9 x 10^-7). After adjusting for age and baseline wound area, the HR for the AlloPatch vs. the control group was 8 (p=3.7 x 10^-7). No adverse events related to the study treatment were reported.

Further investigation is warranted to fully evaluate the safety and efficacy of AlloPatch treatment for DFUs.

AMNIOEXCEL

AMNIOEXCEL is a dehydrated human amnion-derived tissue allograft and is treated as human tissue for transplantation under the FDA’s HCT/P process. There is currently only one available study published on its use in human participants. Snyder (2016) reported on the results of a prospective, open label, randomized, parallel group trial involving 29 adults with type 1 or type 2 diabetes mellitus who have one or more ulcers presenting for more than 1 month with no signs of infection/osteomyelitis. Participants were randomized in a 1:1 fashion to receive treatment with either standard care (SOC, n=14) or AMNIOEXCEL plus SOC (n=15) until wound closure or 6 weeks. The authors reported that 35% of participants in the experimental group achieved complete wound closure at or before week 6 vs. 0% in the SOC group (p=0.017). They observed that there was a more robust response noted in the per protocol population, with 45.5% of participants in the experimental group achieving complete wound closure, while 0% of SOC alone participants achieved complete closure (p=0.0083).

Amniofix

Amniofix is a product that consists of an injectable form of processed allogeneic amniotic tissue and is treated as human tissue for transplantation under the FDA’s HCT/P process. Only one RCT regarding its use has been published in the peer-reviewed published literature. Zelen and colleagues (2013b) report on 45 participants with plantar fasciitis randomized in a single-blind fashion to receive one of three treatments: (1) standard care plus injection with 1.25 cc of sterile 0.9% saline (control group); (2) standard care plus injection with 0.5 cc Amniofix (0.5 cc group), and (3) standard care plus injection with 1.25 cc Amniofix (1.25 cc group). All participants also received injection with 2 cc of 0.5% Marcaine plain, and the use of tramadol for pain was allowed as needed throughout the study. There were 15 participants in each group. A total of 41 participants (91.1%) completed the 8-week follow-up period. All 4 participants who failed to complete the study were in the control group. The authors report that significant benefits were seen in all groups throughout the study compared to baseline on the American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot Scale (p<0.01). Additionally, the AOFAS scale outcomes were significantly higher for both Amniofix groups vs. controls (p<0.001). No differences were noted between the two Amniofix groups. At the end of week 1, the median reduction in pain was 3 points for controls and 6 points and 5 points for those receiving 0.5 cc and 1.25 cc of Amniofix, respectively (p<0.001; p=0.004). Using the Wong–Baker FACES Pain Rating Scale, a visual analog pain scale (VAS), controls reported moderate to severe pain throughout the 8-week study period. Both Amniofix groups reported a significant reduction of pain from very severe at baseline to within the mild to moderate range at 1 week and reported continuing reduction in pain over the study period (p<0.001), with no statistically significant difference between groups. Based upon the physical and mental scales on the SF-36v2 quality of life tool, it was reported that both Amniofix groups had significant improvements from baseline compared to controls. No difference between Amniofix groups was reported. At the end of the first follow-up week, significantly more participants in both Amniofix groups vs. controls needed additional treatment with tramadol (57.1% of controls, 73.3% of the 0.5 cc group, and 100% of the 1.25 cc group). This was not significant for the 0.5 cc group vs. controls but was for the 1.25 cc group vs. controls (p=0.004) as well as the 1.25 cc group vs. the 0.5 cc group (p=0.032). At the second follow-up visit, rates of tramadol use were significantly lower in all groups (p>0.05 for all groups). No adverse events related to treatment were observed in any study participants. This study indicates some benefit from the use of Amniofix for individuals with plantar fasciitis. However, due to the small study population and lack of investigator blinding, further research is warranted to fully understand the efficacy of this treatment method.

Amniotic Allografts – Not specified

There is an increasing body of evidence in the available peer-reviewed published literature addressing the use of allogeneic amniotic tissues for the treatment of a variety of uses, including ophthalmologic, obstetric, and burn conditions. A small number of these publications address branded products, which are addressed elsewhere in this document. However, the vast majority of the published studies involve the use of amniotic-derived products that are: (1) not specified by the authors, (2) branded products not commercially available in the U.S, or (3) materials that are locally sourced. Many of these studies are randomized controlled trials, but with small study populations (Abdulhalim, 2015; Amer, 2010; Andonovska, 2008; de Farias, 2016; Harvinder, 2005; Küçükerdönmez, 2007; Luanratanakorn, 2006; Paris, 2013; Sharma, 2016; Sheha, 2008; Tamhane, 2005; Tandon, 2011). These studies are heterogenous with regard to the type of amniotic graft used, including lyophilized, cryopreserved and glycerin preserved products. Furthermore, there is a wide array of indications addressed across these studies, with a critical mass of evidence not established for any particular one. Finally, due to the differences in the harvesting and processing procedures these materials undergo that may impact the physical properties of the materials, the findings of such studies cannot be used to support the use of amniotic-derived products as a group.

Artacent Wound

Artacent is a product composed of dehydrated acellular human amniotic membrane and is treated as human tissue for transplantation under the FDA’s HCT/P process.

Sledge (2020) reported on a study involving 26 participants who were participants in an RCT that was discontinued due to logistical issues. All participants had non-infected DFUs that had failed previous standard care and were treated weekly or biweekly with Artacent Wound. The primary endpoint of 100% healing at 12 weeks was reported in 17 participants (65%). The incidence of adverse events potentially related to the grafting product was 12% (4/34) and serious adverse events were reported in 6% (2/34).

This data is interesting but does not provide data that is reasonably generalizable to a wider population of individuals with DFUs. Further investigation is warranted.

Artelon (Including CMC and TMC)

Artelon is a synthetic grafting material made from degradable polyurethaneurea cleared through the FDA’s 510K process. - Nilsson, (2010) published the results of an RCT consisting of 109 participants with osteoarthritis of the carpometacarpal joint of the thumb. In this study, 72 participants were treated with Artelon and 37 were treated with standard tendon interposition arthroplasty. There was a significant loss to follow-up, with less than 50% of participants having available data at the 1-year follow-up time point. The authors report that swelling and pain were more common in the Artelon group, and 6 implants were removed because of such symptoms. Interestingly, 5 of these participants did not receive antibiotics preoperatively according to the study protocol. In the intention-to-treat analysis but not in the per-protocol analysis, significantly better pain relief (VAS) was obtained in the control group. Self-perceived disability evaluated by the DASH (disability of arm-shoulder-hand) questionnaire improved in both groups. However, these findings are not particularly useful, given the significant loss to follow-up reported.

At this time, the available peer-reviewed published articles addressing Artelon TMC are case series studies involving 13 and 15 participants each (Jörheim, 2009; Nilsson, 2005; respectively). This level of evidence is inadequate to fully evaluate the safety and efficacy of this product. Further investigation is warranted.

Cuttica (2023) reported the results of a retrospective case series study involving 18 participants undergoing surgical treatment for insertional Achilles tendinosis with tendon repair augmentation using Artelon. The study reported on pain score, strength, and ankle motion. The Wilcoxon signed-rank test was used to compare baseline and final follow-up VAS scores. One participant had 2 suture anchor pull-out from the calcaneus. Final strength was obtained for 17 participants, with 15 (83.24%) reported as being 5/5 and 2 (11.76%) being 4/5. Final active dorsiflexion was measured in all participants, with 17 (94.44%) reaching at least 10°. No participants had evidence of foreign body reaction or neritic complications, required return to the operating room, developed deep vein thromboses, or developed other major complications. The authors concluded that Achilles tendon augmentation with Artelon is a viable option in the treatment and that its use has minimal morbidity and can be an alternative to other forms of augmentation. However, the results of this study are not generalizable due to the low power, lack of a comparison group, and other methodological concerns. Further investigation in the form of rigorously designed and conducted trials is warranted.

Artia

Artia™ reconstructive tissue mesh is a product derived from porcine acellular dermal matrix and cleared through the FDA’s 510K process. King (2023) reported a retrospective non-randomized comparative trial involving the use of Artia for implant-based breast reconstruction in 63 participants vs. 181 participants who received treatment with AlloDerm ADM. Bilateral procedures were done in 95 participants for a total of 276 breasts (n=98 Artia and n=178 AlloDerm). Significantly more participants in the Artia group received prepectoral reconstruction (69.4% vs. 46.6%, p<0.01). Eleven underwent delayed reconstruction, while 265 underwent immediate reconstruction, with no significant difference between groups (p=0.34). Two stage reconstruction with tissue expanders was utilized in the majority of cases (243 breasts), with no difference in reconstruction technique between groups (p=0.2). The authors reported no significant differences between groups with regards to major complications (28.6% vs 31.2%, p=0.69) or minor complications (9.1% vs 14.0%, p=0.24), including hematoma, infection, seroma, dehiscence, necrosis, capsular contracture, and explantation. The results of this study appear to indicate equivalent outcomes between Artia and the standard of care product. However, the small sample size and other methodological issues impair the generalizability if these findings. Further investigation with more robust trials is warranted to establish the clinical utility of this product.

Avance Nerve Graft

Avance Nerve Graft is a decellularized allogeneic product derived from donated peripheral nerve tissue and is treated as human tissue for transplantation under the FDA’s HCT/P process.

A comparative trial involving this product was published by Means in 2016. This double-blind RCT involved 23 participants with 31 digital nerve injuries treated with hollow conduit (n=9) or Avance processed nerve allograft (n=14). The authors reported that the Avance group demonstrated significantly greater recovery vs. conduit participants as measured by results by static 2-point discrimination (5 ± 1 mm vs. 8 ± 5 mm, p<0.5). Among participants with 6-month data available, all participants in the Avance group returned to S3+ (8 of 8 digits) vs. 75% (9 of 12 digits) in the conduit group. A return to S4 was not statistically significant between groups. At 12 months, results of Semmes-Weinstein Monofilament (SWMF) assessment testing found that the Avance group had a significant improvement vs. controls (mean of 3.6 ± 0.7 vs. 4.4 ± 1.4, p<0.05) and recovery of protective sensation, equivalent to SWMF score of 4.31 or better, was reported in 100% of Avance-treated participants vs. 75% of control participants. No differences between groups were found with regard to results on the Disability of the Arm, Shoulder and Hand (DASH) questionnaire or assessment of thermal discretion or pain assessment at 12 months. While this study had a rigorous methodology, the small numbers of participants and significant loss to follow-up (> 70%) hinder the utility of the results.

Brooks and others (2011) reported a case series study involving 108 participants with nerve injuries. Outcomes were only available for 59 participants (56%). The authors report “meaningful recovery” in 87% of participants available for evaluation. A post hoc subgroup analysis demonstrated no significant differences with regard to nerve type, gap length, participant age, time to repair, age of injury, or mechanism of injury (p>0.05). No graft related adverse experiences were reported and a 5% revision rate was observed. The data presented is insufficient to allow full assessment of the safety and efficacy of the Avance nerve graft.

Safa (2019) reported a case series study involving data from the RANGER^® registry involving 385 participants who underwent 624 nerve repair procedures using Avance and were compared to historical data from participants undergoing hollow tube conduit and/or autografts. Follow-up was 12 months for sensory nerves and 18 months for mixed/motor nerves. Overall response rate was reported to be 87%, with response being defined as “any improvement after repair based on either qualitative and/or quantitative assessments”. Meaningful recovery, defined as S3 or M3 or greater improvement as measured by the Mackinnon-Dellon Modification of the Medical Research Council Classification (MRCC) sensory and motor scale, was reported as 82% of participants. By body region, meaningful recovery was reported as 83%, 53% and 100% for the upper and lower extremity and head/neck, respectively. The difference between upper and lower extremity was significantly different (n=0.01). Compared to historical comparisons, the author’s findings were not significantly different. For upper extremities, nerve gap lengths < 15 mm had significantly better meaningful recovery than those 50-70 mm (p=0.011). No differences in meaningful recovery stratified by gap length were reported for the lower extremities.

Ilyas (2024) reported a multicenter US based RCT that included 220 participants with digital nerve injuries treated either with type I bovine collagen conduit (CONDUIT) or a PNA. The CONDUIT group used the NeuraGen Nerve Guide, the PNA group used the Avance Nerve Graft. Inclusion criteria was individuals 18- to 69-years with 5 to 25 mm digital nerve gaps within 24 weeks of injury. Participants were randomized (1:1) to PNA or CONDUIT repairs. Cold Intolerance Symptom Severity (CISS) scores and sensory function testers were assessed at first visit (FPV), 1-, 3-, 6-, 9-, and 12-months post-surgery, both participants and assessors were blinded to treatment. One hundred eighty-three participants completed the last evaluable visit (LEV) of 6 months or more of follow-up. Of these, 91 received PNA repair and 92 had CONDUIT repair. No significant differences were observed in demographics, gap length, time to repair, or injury mechanism between the groups. The average gap lengths were 13.6 mm for the PNA group and 13.0 mm for the CONDUIT group. The average time to repair was 28.2 and 23.4 days, respectively. Both groups reported a reduction in the CISS over time, indicative of improved cold intolerance symptoms. The mean CISS score for the entire cohort decreased from 31.15 ± 29.25 at FPV to 23.42 ± 22.16 at the LEV. The reduction in CISS score was numerically greater but not statistically different in the PNA group (10.39 points) compared with the CONDUIT group (5.23 points). A sub-analysis showed more participants improved from severe/extremely severe cold intolerance to mild cold intolerance for PNA compared with CONDUIT at 1 month and LEV (p < 0.05). The CISS scores also correlated with sensory function testing. The authors concluded that PNA had improved cold tolerance outcomes for participants with more severe cold intolerance at FPV relative to nerves repaired with CONDUIT. Study limitations include the loss to follow-up at later timepoints in the study; at the 1-month timepoint, the study had a total of 178 participants, but by 12 months, only 149 were available for evaluation. Target follow-up for the study was 12 months; however, participants were assessed at or greater than 6 months, which included up to 15 months out from repair. The study did not include a sub-analysis of participants who concomitantly underwent vascular repair. This was due to a low overall number of participants with vascular injury requiring repair, which is likely a result of the exclusion criteria of the study as well as study design limitations. This limits the generalizability of this study to individuals with nerve injuries who do not require vascular repair.

The results of these studies are promising. Further data from more rigorously designed and executed studies is warranted.

Avaulta

Avaulta is a composite product composed of polypropylene mesh with acellular cross-linked collagen of bovine origin and has been cleared through the FDA’s 510K process. The use of Avaulta Plus and Avaulta Biosynthetic Support System for the treatment of vaginal prolapse has been described in one prospective case series study involving 40 participants (Bondili, 2012). Participants were followed for up to 3 years (median 27 months (range 20-36). The primary outcome was quality of life (QoL) and satisfaction as measured by the International Consultation on Incontinence Modular Questionnaire–Vaginal Symptoms (ICIQ-VS) tool. Twelve participants (30%) were undergoing a second procedure to address prolapse. Of the 40 participants, 19 (47%) underwent anterior repair, 20 (5%) posterior repair, and 1 (2.5%) underwent both anterior and posterior procedures. Vaginal laxness improved significantly, with 67.25% of participants reporting preoperative laxness which improved to 5% of participants with laxness at follow-up (p<0.0001). Decreased vaginal sensation also improved, from 30% to 7.5% (p<0.01). Sexual activity was reported to improve from only 32% to 100% postoperatively. The authors report that 1 participant continued to have prolapse symptoms (2.5%), resulting in a 97.5% success rate (p<0.0025). Only 2 participants (5%) needed to digitate the vagina to vacate their bowels, a significant decrease from 12 (57%) preoperatively (p<0.001). Vaginal pain decreased from 55% preoperatively to 2.5% postoperatively (p<0.0001). No surgical complications were mentioned.

A retrospective case series study by Oliveira and colleagues (2020) involved 97 participants with ≥ stage II genital wall prolapse repair with Avaulta. Mean follow-up was 2.9 years with 12 participants lost. Postoperative complications were experienced by 29.1% (n=23) of participants, with one removal due to hematoma. Other complications included voiding dysfunction (n=10), urinary infection (n=7), vesicovaginal fistula (n=1), pelvic abscess linked to hysterectomy (n=2), and mesh exposure (n=6). For participants with voiding dysfunction and bladder injury, a prolonged bladder drainage by a Foley catheter was required for a mean duration of 11.2 days. Four of the participants with vaginal mesh exposure required additional surgery to partially remove the mesh in 3 cases and a colpoplasty procedure to cover the mesh in the remaining case. Self-reported improvements were reported with regard to vaginal discomfort (n=79 at baseline vs. 4 at last follow-up, p>0.01), pelvic heaviness (n=46 at baseline vs. 3 at last follow-up, p>0.01), and voiding dysfunction (n=16 at baseline vs. 2 at last follow-up, p>0.01). No anterior wall prolapse was present in 79.1% of participants at last follow-up and stage I and II prolapse was reported in 19% and 3%, respectively. No apical and posterior prolapse was reported in 98.5% and 83.6%, respectively. Eight participants (12 %) had recurrence at 3 years.

The results of these uncontrolled case series are promising. Further data from more rigorously designed and executed studies is warranted.

Avive

Avive Soft Tissue Membrane is a product derived from allograft amnion and umbilical cord membrane, which is regulated through the U.S. FDA’s HCT/P process as human tissue for transplantation.

Cox (2023) reported the first use of Avive in a prospective propensity-matched cohort study involving 77 participants (97 nerves) who underwent revision nerve decompression. Mean follow-up was 9.0 months. Avive was applied to the median nerve in 47.4% of cases, ulnar nerve in 39.2% of cases, and radial nerve in 13.4% of cases. In the Avive cohort, S4 sensory recovery was achieved in 58% of participants, S3+ in 33%, S3 in 7%, S0 in 2%, and improvement from baseline in 87%, strength was improved in 92%. Mean total active motion was 94.8%. Mean Quick Disability of Arm, Shoulder & Hand (QuickDASH) score was 36.1, and 96% reported improved or resolved symptoms. For between-group comparisons, postoperative pain was significantly lower in Avive group participants (p=0.001). Improved or resolved symptoms were more frequently reported in the Avive group (p<0.0001). Finally, clinically important improvement in pain was reported in 64.9% in the Avive group vs. 40.8% the control group (p=0.002). This initial pilot study indicates some benefit to the use of Avive in revisions nerve surgery. Further investigation is needed to fully understand the benefits and harms of such use.

BEAR (Bridge-Enhanced ACL Repair) Implant

In December 2020, the FDA granted De Novo approval of the BEAR Implant (Miach Orthopaedics Inc. Westborough, MA). BEAR is a decellularized xenograft derived from bovine collagen and is indicated for repair of anterior cruciate ligament tear (ACL). The graft implant is combined with autologous whole blood to form a clot that replaces the ACL and functions as a bridge between the torn ends of the ligament.

Murray (2020) and Barnett (2021) both reported the results of the BEAR II trial, a double-blind RCT involving 100 participants aged 13-35 years with a complete midsubstance ACL injury treated with BEAR (n=65) or autograft ACL (n=35). Participants underwent surgery within 45 days of the index injury. Participant outcomes were assessed at 2 years by an independent examiner blinded to the procedure. Murray reported that the results on the International Knee Documentation Committee (IKDC) Subjective Score were 88.9 points for the BEAR group and 84.8 points for the control group (no p-value reported). The side-to-side difference in AP knee laxity in the BEAR group was 1.61 mm vs 1.77 mm in the control group (no p-values reported). The BEAR group had a significantly higher mean hamstring muscle strength index than the control group at 2 years (98.2% vs 63.2%; p<0.001). The report by Barnett stated that repeated-measures testing revealed a significant effect of group on the IKDC Subjective Score (p=0.015), most pronounced at 6 months after surgery (86 points in the BEAR group vs. 78 points in the control group; p=0.001). Results on the Knee Injury and Osteoarthritis Outcome Score-Symptoms subscale scores were significantly in favor of the BEAR group (p=0.010) attributable to higher BEAR scores at 1 year (88 vs 82; p=0.009). Hamstring strength was significantly better in the BEAR group vs. controls (p<0.001). Clearance for return to sports at 1 year after surgery was granted to approximately 88% of BEAR group participants and 76% of control group participants (p=0.261). The authors concluded participants undergoing the BEAR procedure had earlier resolution of symptoms as well as increased satisfaction with knee function and hamstring muscle strength.

Another study by Barnett (2020) also compared sex-specific outcomes following ACL reconstruction within 45 days of injury in 65 participants with complete ACL tear treated with BEAR. The results demonstrated no significant sex difference on the postoperative IKDC Subjective Score or any of the five Knee Injury and Osteoarthritis Outcome (KOOS) scores at 12 and 24 months. Additionally, AP laxity testing demonstrated differences that were similar in the two sexes at 2 years (1.7 mm and 1.5 mm in females and males, respectively; p=0.72). At 6 months postoperatively, males had a larger deficit in hamstring strength on the operated leg (14.0% vs. 1.7%; p=0.03) and a larger deficit in quadriceps strength on the operated leg (11.3% vs. 2.0%; p=0.004); however, no differences were noted at 12 or 24 months. Interestingly, females demonstrated superior single leg hop testing at both 6 and 12 months (91.3% vs. 78.1%, p=0.001 and 96.9% vs. 87.0%, p=0.01, respectively). No significant differences were reported with regard to ipsilateral ACL reinjury rates.

Menghini and others (2022) completed a cohort study using data from the above-mentioned BEAR II trial, examining the cross-sectional area (CSA) of the treated vs. contralateral native ACLs (n=65 in the BEAR group, n=35 in the autograft group, n=100 in the native group). CSA is a known predictor of strength and knee function. The authors reported that at 24 months, CSA in the autologous group peaked at 69%, 61% in the BEAR group, and 42% in the native group, with significant between-group differences (p<0.001). They concluded that while the BEAR ACLs remained significantly larger, the autograft ACL had a CSA profile comparable with that of the contralateral native ACL.

Flannery and colleagues (2023) reported the results of a retrospective analysis of 65 individuals from the BEAR II RCT, that compared BEAR graft to traditional ACL reconstruction using non-contemporaneous quantitative MRI to predict positive functional outcomes from 6-24 months post-ACL surgery. The study images were obtained at 6 months post-surgery, additionally single-leg hop test ratios, arthrometric knee laxity values, and IKDC subjective scores were measured at 6 and 24 months. The results demonstrated that CSA (r=0.44, p=0.01), volume (r=0.44, p=0.01), and estimated failure load (r=0.48, p= 0.01) measures at 6 months were predictive of the change in single-leg hop ratio from 6 to 24 months in bivariate analysis. The authors concluded that using qualitative MRI at 6 months post-surgery may be a predictor of longer term functional outcomes. This information may be useful in rehabilitation planning, return to sport decisions, and injury risk reduction.

The use of BEAR Implant for the treatment of ACL injury in the published literature is promising. However, the totality of evidence does not yet support a durable equivalent to standard of care ACL reconstruction. Further investigation is needed in the form or rigorous, well-designed comparative trials.

Belladerm

BellaDerm is a product composed of acellular human dermis and is treated as human tissue for transplantation under the FDA’s HCT/P process.

Solomon and others (2013) published the results of a retrospective case series study involving 47 participants who underwent penis girth enhancement utilizing circumferential grafting with allograft material. The participants received either aseptic AlloDerm (n=9), Belladerm (n=20), and Repriza (n=21). Mean follow-up was 11.25 months (range 1 to 120 months). The rate of infection, which the authors defined as an open wound with graft exposure, occurred in 20 (42%) of 47 participants. Of these, 17 (36%) participants had graft exposure only and 3 (6%) participants sustained graft exposure and total graft loss. Graft exposure or loss occurred in 3 AlloDerm participants, 9 Belladerm participants, and 8 Repriza participants. No AlloDerm participants sustained graft loss, whereas 2 with Belladerm and 1 with Repriza did. No statistical differences between groups with regard to infection or graft loss was reported.

This study’s methodology is t insufficient to assess the safety or efficacy of any of these products for this procedure.

BioBrace^™ Implant

BioBrace^™ Implant (CONMED Corp., Largo, FL) is a bioresorbable scaffold designed for surgical reinforcement of weakened soft tissues. Made from bovine tendon collagen and reinforced with polyL-lactic-acid (PLLA) yarn, it supports tissue healing in surgeries such as tendon repairs, including rotator cuff, patellar, Achilles, biceps, and quadriceps tendons. The device received FDA clearance through the 510(k) process.

Biodesign Please see ‘Surgisis’ section below.

CardioCel

CardioCel is a product produced from bovine pericardial tissue and has been cleared through the FDA’s 510K process. At this time, the available published in the peer-reviewed literature addressing this product is limited. Pavy (2017) published the results of a retrospective series of 102 participants who underwent procedures addressing variety of congenital heart diseases, including septal defects to pulmonary outflow disorders. No infections, intraoperative implantation difficulties or postoperative mortality were reported to be associated with CardioCel. Graft failure reoperations occurred in 5 participants (5%), 4 of whom had the patch implanted for aortic angioplasty (2 in the ascending aorta and 2 in the aortic arch), and 1 participant had a monocusp replacement. The median time between the first and the second operation for graft failure was 245 (range 5-480) days. The authors concluded that, “Our experience shows that the patch is well tolerated in the septal, valvar and pulmonary artery positions. However, we experienced graft failures in infants in the aortic position.”

Bell and colleagues (2019) reported on the results of another series study involving 377 participants with congenital heart defects who received surgical treatment with 501 CardioCel patches. Median follow-up was 31 months (1-60 months), and 11 deaths (2.9%) were reported, with 1 reportedly related to Cardiocel. The authors reported no echocardiographic or radiological evidence of patch calcification in any participant. The overall freedom from reintervention at 3- and 5-years post-implantation was 96%. A total of 14 (2.8%) implants required 18 reinterventions (3.6%) at the site of implantation. No differences in performance of CardioCel in neonates (0-28 days), infants (29-365 days) or children older than 1 year (p=0.22) were reported. Patukale (2023) reported on the mid-term performance of CardioCel for the repair of congenital heart defects. The retrospective study included a total of 1184 CardioCel patches implanted in 752 pediatric participants. Median age at implant was 12 months with median follow-up of 2.1 years. The authors reported the probability of freedom from CardioCel-related reintervention as 93% at 1 year, 91% at 3 years, and 88% at 5 years, respectively. A multivariable regression analysis indicated that participants undergoing aortic valve repair had a higher incidence of reintervention vs. other sites (HR, 7.15, p=0.008). They also stated that the probability of reintervention was higher in neonates (HR, 6.71, p=0.0007), especially when used for augmentation of the pulmonary arteries (HR, 14.38, p=0.029). This study indicates that CardioCel may be used for the repair of a variety of congenital heart defects. However, reinterventions were higher when CardioCel was used to augment the pulmonary arteries in neonates and for aortic valve repair as compared to other sites. This outcome needs further elucidation before the use of CardioCel can be widely used.

These results are promising, but data from larger, well-designed studies is needed to fully understand the safety and efficacy of CardioCel use in the repair of congenital heart diseases.

CellerateRX

CellerateRX Surgical Hydrolyzed Collagen Powder (Sanara Med Tech, Fort Worth, TX) is a bovine collagen derived product cleared through the FDA’s 510(k) process and intended for surgical wound management. A retrospective nonrandomized, controlled study by Sultan (2024) involving 76 individuals undergoing spinal fusion with paraspinal flap reconstruction evaluated the use of CellerateRX (n=47) vs. standard care (n=29) . Compared to the standard care group, the CellerateRX group had a higher rate of seroma formation (approximately 28% vs. 7%, p=0.03), but no significant differences in wound dehiscence (p=0.17), hematoma (p=1.0), infection (p=0.58) or reoperation (p=0.58)s. Additional well-designed research with larger, more diverse populations and longer follow-up is warranted.

Clarix

Clarix is a product composed of cryopreserved acellular human amniotic membrane and umbilical cord and is treated as human tissue for transplantation under the FDA’s HCT/P process.

Bemenderfer (2019) provided the only currently available published peer-reviewed study on this product. The unblinded non-randomized study involved 104 participants undergoing total ankle arthroplasty who received skin closure with either Clarix (n=54) or standard care (n=50). The authors reported that use of Clarix significantly decreased the overall time to skin healing (28.5 days vs. 40 days; p=0.03). No differences between groups were reported with regard to reoperations, skin dehiscence, local wound care, or antibiotic prescriptions. These results are promising, but additional data from larger controlled studies is needed to understand the safety and efficacy of this product.

Ross and colleagues (2022) reported a single center, retrospective study of pain outcomes in 52 individuals with musculoskeletal spinal disorders who were treated with ClarixFLO via epidural and facet injections. Conditions treated included; spondylosis (n=44), intervertebral disc (n=31), radiculopathy (n=18), stenosis (n=2), and other conditions. Pain was rated by participants on a scale of 0-10 where 0 indicated no pain and 10 indicated the worst imaginable pain. The average baseline pain score was 4.9, the mean duration of symptoms was 54.2 months. After ClarixFLO treatment, pain ratings decreased to 3.4 at 2 weeks (p< 0.0001) and 3.5 at 3-4 weeks (p=0.0023). During the follow-up period (average 10.6 weeks), pain was reduced to 2.8 (p< 0.0001) compared to baseline. There were no adverse events reported, and the authors concluded that additional larger studies are needed to confirm the safety and efficacy of ClarixFLO in epidural and facet injections.

Madan (2023) published a study that analyzed the use of ClarixFLO in the treatment of cystitis and bladder pain. In the first study, 5 natal females average age 64.4 (± 20.1 years) who had a median chronic radiation cystitis (CRC) duration of 10 years that was refractory to previous treatment modalities, received amniotic bladder therapy with ClarixFLO. The therapy was comprised of intra-detrusor injections of 100 mg micronized ClarixFLO diluted in 0.9% preservative-free sodium chloride. Outcomes measured were the Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, and SF-12 Health Survey prior to surgery and 2, 4, 8 and 12 weeks post-injection. After treatment with ClarixFLO the BPIC-SS scores improved from baseline to 12 weeks (36.6 compared to 12.6); this was also associated with an improvement in ICSI, ICPI, OAB, and SF-12 scores. Additionally, uroflow assessments showed increases in voided volumes for all individuals. One individual was diagnosed with an acute urinary tract infection at 2 weeks which was treated successfully with oral antibiotics. No other adverse events were observed. The authors concluded that the results provide proof of the potential benefits of ClarixFLO in treating CRC.

A study by Radoiu (2023) involved 10 natal females aged 47.4 (± 14.4 years) with interstitial cystitis/bladder pain syndrome (IC/BPS) that had been refractory to previous treatment modalities for an average 7.8 years who received intra-detrusor injections of 100 mg ClarixFLO diluted in 0.9% preservative-free sodium chloride. Again, the outcomes measured were the ICSI, ICPI, BPIC-SS, Overactive Bladder Assessment Tool, and the SF-12 Health Survey prior to surgery and 2, 4, 8 and 12 weeks post-operatively. After treatment with ClarixFLO, voiding symptoms and bladder pain improved from pre-injection to 3 months. BPIC-SS decreased from 37.4 at baseline to 12.2 at 3 months (p< 0.001). There were no adverse events reported. The authors concluded that ClarixFLO may be a treatment option for individuals with IC/BPS symptoms based on the preliminary results. While these 2 small studies are promising, additional larger studies with longer endpoints are needed to confirm the clinical efficacy and durability of ClarixFLO in treating cystitis and BPS.

In a single-center, retrospective case series study by Krystofiak (2024) Clarix Flo was used to treat acute muscle or ligament tears in 10 collegiate athletes. The authors reported an average return to play of nearly 30 days, with no complications observed. These preliminary results suggest potential to expedite recovery with Clarix Flo, but additional high-quality investigations with larger, more diverse populations and longer follow-up are warranted.

A controlled retrospective study involving 113 individuals undergoing meniscectomy was reported by Duru (2024). Treatment with platelet rich plasma was done in 40 participants, treatment with Clarifix Flo in 24 participants, and no adjunctive therapy was done in 49 participants. The authors reported significant differences at baseline between the groups with regard to sex, age, and International Cartilage Repair Society (ICRS) classification grade (p<0.05). The average VAS pain severity was significantly decreased only in the Clarifix Flo group at 6 months, compared to baseline (p=0.0143), but not at 12 months (p=0.12). No significant differences in pain severity of frequency were noted in the platelet rich plasma or no adjunctive therapy groups through 12 months. At 12 months. No differences between groups were reported with regard to Lysholm Knee Scoring Scale, IKDC Subjective Knee Evaluation Form Scores or overall, Knee Injury and Osteoarthritis Outcome Score results. The Clarifix Flo group did demonstrate a reduced reoperation rate (8.3%) compared to the platelet-rich plasma (30%) and no adjunctive therapy groups (40.8%, no p-values provided). However, the single-center design, retrospective methodology, and relatively short follow-up limit the conclusiveness of these findings. While these results indicate some potential benefit, additional high-quality trials with larger, more diverse cohorts and longer follow-up are necessary.

While these results are promising, further investigation in the form of more robust, well-designed and executed studies is needed to fully elucidate the clinical utility of ClarixFlo.

Conexa

Conexa is a product produced from acellular porcine dermis and has been cleared through the FDA’s 510K process. At this time, the only comparative trial published in the peer reviewed literature addressing the use of this product was reported by Maillot and others in 2018. This prospective non-randomized trial involved 32 consecutive participants with large-to-massive rotator cuff tears assigned to treatment with 1) arthroscopic complete repair (repair group), 2) open repair and xenograft patch augmentation (patch group), or 3) arthroscopic debridement and tenotomy of the long head of the biceps (debridement group). Participants were evaluated preoperatively and postoperatively at 3, 6, 12 and 24 months. The authors reported that the mean improvement in the Constant-Murley score was +29.1, significant for all groups at the final follow-up examination (p<0.01 for all). No differences were reported between the repair and patch groups. However, comparison between the debridement group and the patch group at 12 months and the final follow-up was significant (p<0.001), as was the comparison between the debridement group and the repair group (p<0.002). Complications occurred in 5 of 11 participants in the patch group and only 1 in the repair group and none in the debridement group. The authors concluded that “the use of porcine dermis patches to augment repairs of massive and irreparable rotator cuff tears is not recommended because there is no benefit compared with repair without augmentation and patches result in more complications.”

CorMatrix

CorMatrix is a product produced from acellular porcine small intestinal submucosa and has been cleared through the FDA’s 510K process. At this time, there is very limited peer-reviewed published evidence addressing the use of CorMatrix. The data that is available addresses its use in cardiovascular surgical procedures. The largest of these studies is a retrospective, nonrandomized control study involving 111 participants undergoing coronary artery bypass surgery (CABG) who had pericardial reconstruction with CorMatrix, compared to 111 control participants who underwent a standard CABG procedure without pericardial reconstruction (Boyd, 2010). The authors reported that postoperative atrial fibrillation occurred in 39% of controls vs. 18% of CorMatrix participants. No other results were significantly different. The safety and value of CorMatrix is difficult to interpret in this study, as it is the pericardial reconstruction procedure that seems to be the significant variable. Another publication by Quarti and colleagues (2011) describes the use of CorMatrix in a wide variety of cardiovascular surgeries, with no comparison groups provided. While the authors report no significant complications due to the use of CorMatrix, this study provides little in the way of helpful data to determine the safety and efficacy of this product. Similarly, Kelley and others (2017) reported the results of a retrospective case series study of 25 participants who underwent anterior leaflet augmentation. They reported a 32% recurrence rate of mitral regurgitation and concluded that further research is needed. Finally, Ashfaq (2017) reported good results from the use of CorMatrix in an case series of 15 pediatric participants undergoing atrioventricular (AV) septal defect repair. They reported 12 (80%) participants either improved or had stable left AV valve performance remaining at "mild" or less insufficiency, two (13%) declined from "none" to mild, and one (7%) from declined from mild to "severe," No residual shunting or left ventricular outflow tract (LVOT) obstruction was noted at follow-up. Only one (7%) reoperation was performed after 3 years due to left AV valve zone of apposition dehiscence. No permanent pacemakers were needed, and no deaths were reported.

Hu and others (2021) reported the results of a retrospective cohort study of 38 pediatric participants undergoing aortic valve repair with the aortic cusp extension procedures with either autologous pericardium (n=30) or CorMatrix (n=8). The authors reported that for the entire cohort the peak trans‐valvular gradient significantly decreased immediately postoperatively (p=0.0017). No significant changes were observed at the 5-year follow‐up timepoint (p=0.36). In the autologous group participants with aortic stenosis at baseline the peak trans‐valvular gradient did not significantly change at follow‐up (p=0.12). The CorMatrix group had only 4 participants with aortic stenosis at baseline, which did not allow for sufficient data for between‐group tests. Moderate-to-severe aortic regurgitation was reported in 28 (93%) of autologous group participants at baseline, which improved to 11 (37%) postoperatively, but increased to 21 (70%) at follow‐up. Eight (100%) CorMatrix group participants had moderate-to-severe aortic regurgitation, which improved to 3 (38%) postoperatively and increased to 7 (88%) at time of follow‐up. Between‐group data indicated a significant difference in favor of the autologous group (p=0.017). Freedom from reoperation at 5 years was significantly poorer in the CorMatrix group (12.5%) vs. the autologous group (62.5%, p=0.01). The most common reason for reoperation in the autologous group was for repair of moderate to severe aortic regurgitation and severe aortic regurgitation in the CorMatrix participants. While no CorMatrix participants had severe aortic regurgitation postoperatively, 88% developed it at 5 years follow‐up. The authors concluded that autologous pericardium may outperform CorMatrix for aortic valve repair using the cusp extension method. However, several methodological weaknesses of this study limit the generalizability of these findings and further study is warranted.

Overall, the data regarding the safety and efficacy of CorMatrix is incomplete and conflicting. Further investigation with larger well-designed trials is needed.

Cymetra

Cymetra, an injectable micronized particulate form of aseptic AlloDerm (decellularized human dermis), has been proposed as a minimally invasive tissue graft product. It is treated as human tissue for transplantation under the FDA’s HCT/P process. At this time, there are only three peer-reviewed published articles addressing the use of this product. All of these studies involve participants with vocal cord paralysis. One study by Morgan and colleagues (2007) was a retrospective, nonrandomized controlled trial involving 19 participants undergoing injection laryngoplasty with Cymetra or medialization laryngoplasty. The authors reported no significant difference between groups at 3 months follow-up. No long-term comparison data was provided. Another report of a retrospective case series study involving 10 participants who all received injection laryngoplasty was reported by Milstein et al (2005). The authors of this study reported significant improvement in voice quality, glottal closure, and vocal fold bowing. Of the study population, only 8 participants (40%) were found to have lasting benefit. Finally, Karpenko and others (2003) reported the results of a case series study (n=10). The results indicated that there were no significant quantitative or subjective voice quality improvements. They also stated that significant improvements were identified in maximum phonation time, relative glottal area, and subjective judgment of glottal competency. However, these results were not maintained at the 3-month study interval.

Cytal™

Cytal Matrix™ Wound Matrix is a product derived from porcine bladder epithelial basement membrane and tunica propria and has been cleared through the FDA’s 510K process.

Huen (2022) published a retrospective case series study involving 10 pediatric participants undergoing corporal graft and correction of ventral curvature in proximal hypospadias repair. Median follow up was 14.1 months. Mean ventral curvature after degloving was 80 ± 50 degrees. All participants had straight erections at baseline and 9 had straight erections verified at a subsequent artificial erection test at least 6 months from the corporoplasty (90%). The remaining participant underwent a further procedure and had straight erections per parental history. No participants developed corporal diverticulum or demonstrated induration at site of corporoplasty on physical exam. There were no parental reports of atypical adverse systemic effects. This unique use of a graft product may provide some clinical benefit. However, the clinical utility should be established in larger, more robust trials.

Dermacyte^™ Amniotic Wound Matrix

Dermacyte™ (Merakris Therapeutics, Triangle Park, NC) is an amniotic membrane allograft regulated by the FDA under HCT/P process as human tissue for transplantation. Ditmars (2024) described the results of a multicenter retrospective trial involving 11 individuals with a total of 18 refractory diabetic or venous leg ulcers with Dermacyte. Ulcer volumes decreased by about 34% after the first application (p<0.005; 95% confidence interval [CI], –0.5319 to –0.1790), and most ulcers reached a 50% reduction in size after about three applications (p<0.0001). Both ulcer types showed rapid improvement, although healing trajectories varied, especially among “rapid responders.” While these findings appear promising, the small study population, short follow-up period, further high-quality research with larger, more diverse cohorts is warranted.

Derma-Gide

Geistlich Derma-Gide® (Geistlich Pharma, Princeton, NJ) is a porcine collagen xenograft sheet designed to manage various types of wounds, including partial and full thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, surgical wounds (donor sites/grafts, post Moh’s surgery, post laser surgery, podiatric, wound dehiscence), and traumatic skin wounds (abrasions, laceration, second degree burns, skin tears). Cleared by the FDA’s 510K process, Derma-Gide was the subject of a 2024 multicenter prospective, parallel-group RCT comparing its efficacy to standard of care (SOC) for treating full-thickness, non-infected, non-ischemic diabetic foot ulcers (DFUs) (Armstrong, 2024). SOC consisted of a moisture-retentive, conformable collagen alginate dressing. The study included 105 participants who were randomized to either of two treatment groups (n=54 PRBM; n=51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n=47 PRBM; n=33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing and quality of life. The proportion of wounds healed at 12 weeks in the PRBM was 83% vs. 45% for SOC, p=0.00004. The time to heal within 12 weeks was shorter in the PRBM group, 42 days compared to 62 in SOC, p=0.005. The PAR values at 12 weeks was a mean of 93.6 for the PRBM participants compared to 50.5 for SOC. The DFUs treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, , PP: 92% vs. 67%, p=0.005). Wounds treated with PRBM also healed faster than those treated with SOC; mean of 42 versus 62 days for SOC (p=0.00074) and mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p=0.0023). In the SOC group, 17 participants were withdrawn or lost to follow-up. A total of 14 were withdrawn due to the index ulcer presenting a PAR <50% at week 6, while one participants ulcer was reopened at the healing confirmation visit. Additionally, two participants were removed due to adverse events, but there was reportedly no causal relationship between the adverse events and the treatment. While the results of the RCT are promising, limitations include the small trial size, exclusion of some SOC participants from the final analysis, and focus on a single DFU type which limits generalizability of the results. Future large heterogenous studies are needed to confirm the findings.

DermaPure^™

DermaPure^™ is an acellularized human skin-derived product regulated through the FDA’s HCT/P process as human tissue for transplantation. In a retrospective case series by Corlee (2024) of 42 participants diagnosed with insertional Achilles tendinopathy, individuals underwent partial detachment of the Achilles tendon, excision of the retrocalcaneal exostosis, thorough debridement, and repair augmented with DermaPure without suture anchor reattachment. Over a mean follow-up of 20.8 months, the average visual analog scale score improved from 5.1 to 1.9, and participants achieved weight-bearing at an average of 4.4 weeks. Of the 42 participants, 11 (26.2%) experienced complications, including a single rupture (2.4%) in the early postoperative period. No infections were reported, and 4 participants (9.5%) required reoperation. The authors suggest that these findings indicate acellular dermal matrix augmentation without anchor fixation can offer satisfactory outcomes and may justify further investigation under controlled, comparative designs. Nevertheless, the study’s retrospective design and relatively small sample size limit broader generalizability. Additionally, the high complication rate raises concern that warrants investigation in a more rigorous trial.

DuraGen

DuraGen is made from bovine Achilles tendon collagen and is treated with a proprietary process to remove antigenic components. The graft is a porous scaffold that is purported to promote rapid fibrin clot formation while promoting natural dural growth it is contours to surfaces of the brain and spinal cord forming a biological seal to protect against CSF leakage.

Hamrick and colleagues (2023) performed a retrospective, single-center study of 106 individuals who had Chiari decompression surgery by a single surgeon. The study compared the incidence of graft-related complications after posterior fossa surgery using AlloDerm alone compared to AlloDerm with a DuraGen underlay. The inclusion criteria were ≥ 18 years of age, radiographic and clinical findings of Chiari 1 malformation. The exclusion criteria were individuals younger than 18 years, had a previous Chiari decompression, or had Chiari type 2 with associated spina bifida. The AlloDerm-only group had a percutaneous cerebrospinal fluid (CSF) leak rate of 8.6% versus a 0% rate in the dual graft group (p=0.037). At initial follow-up, there was a 15.5% combined rate of pseudomeningocele formation plus CSF leak in the AlloDerm-only group, and 18.8% in the AlloDerm plus DuraGen group (p=0.659). However, the pseudomeningoceles were larger in the AlloDerm-only group (p=0.004) and 5 individuals in the group required surgical repair (56%). All pseudomeningoceles resolved without the need for surgery in the AlloDerm plus DuraGen group (p=0.003). The authors concluded that DuraGen underlay with a sutured AlloDerm dural patch resulted in fewer CSF-related complications and eliminated the need for reoperation compared with AlloDerm alone. This single-center study provides promising evidence that dural grafts with a DuraGen may decrease the risk of complications, however larger RCT’s are needed to analyze the efficacy of DuraGen in reducing rates of postoperative pseudomeningoceles and cerebrospinal fluid leak following Chiari decompression surgery.

Xu (2023) completed a retrospective case series review of 1011 individuals who had an open surgical procedure for microvascular decompression using a retrosigmoid approach. The study objective was to identify factors that may lead to CSF leak after a microvascular decompression procedure. Of the individuals who had the procedure, 37 (3.7%) presented with postoperative CSF leaks. Individuals with and without CSF leaks were not statistically different in age, sex, BMI, diagnoses, prior treatment, or comorbidities. In both groups most individuals presented with Type I trigeminal neuralgia. The results demonstrated that CSF leak after a craniotomy occurred more frequently compared with a craniectomy (13.5% compared to 3.0%), p=0.001. Individuals were more likely to develop a CSF leak with closure of air cells with bone wax, (p=0.002) and compared to the use of Cranios/Norian bone cement, (p=0.01), CSF leak rates were higher with the use of both Durepair (dural substitute) or DuraGen (dural onlay), p=0.04. The authors concluded that the results showed an increased risk for postoperative CSF leak when primary dural closure was not established. Creating a water-tight closure of the dura, regardless of dural substitutes and other dural overlays may be critical to decrease the risk of CSF leaks and postoperative outcomes. Due to the small sample size additional studies are needed to confirm the findings.

DuraMatrix-Onlay/ DuraMatrix-Onlay® Plus, DuraMatrix Onlay

DuraMatrix (Collagen Matrix Inc, Oakland, NJ) is a suite of products derived from acellular bovine Achilles tendon and has been cleared through the FDA’s 510K process. It is indicated for surgical dural repair and prevention of CSF leak Mekonnen (2023) described a retrospective case series study involving 33 participants who underwent a duraplasty procedures using DuraMatrix-Onlay^® Plus collagen dura membrane. The majority of procedures were elective operations for the resection of a lesion (n=19, 58%). Average graft size was 17.69±4.73 cm². At a mean follow-up of 3 months, no postoperative CSF leaks were reported. The rates of infection, dural substitute complication, and removal were 6%, 6%, and 3%, respectively. The clinical utility of this product warrants further investigation in more robust trials.

In 2019 the FDA published a Manufacturer and User Facility Device Experience (MAUDE) event that included 4 individuals treated with Onlay Plus. During the review of post-op scans, images showed what appeared to be an infection on the brain that required surgery. Upon exploration, the surgeon observed what looked like puss lying on the brain, cultures were taken and were reportedly negative. The surgeon concluded that the puss was actually DuraMatrix Onlay Plus that had turned into a "soup" like substance. Subsequently in 2022, the FDA issued a Class 2 device recall for DuraMatrix Onlay due to a breached outer pouch seal compromising sterility and resulting in potential risk of patient infection, which could lead to revision surgery

DuraMatrix Suturable

DuraMatrix® Suturable (Collagen Matrix Inc, Oakland, NJ) is a product derived from bovine dermis collagen and has been cleared through the FDA’s 510K process. It is indicated for surgical dural repair and prevention of CSF leak.

DuraSorb

DuraSorb^® (Polydioxanone Surgical Scaffold) (Integra Life Sciences, Princeton, NJ) is a fully-resorbable knitted mesh indicated for use in reinforcement of soft tissue where weakness exists. DuraSorb was cleared through the FDAs 510k approval process.

Enduragen

Enduragen is a product composed of porcine acellular dermal matrix and has been cleared through the FDA’s 510K process. McCord and others (2008) have published the only available study addressing the use of Enduragen. Their retrospective case series involved 69 participants who underwent 192 reconstructive or cosmetic eyelid procedures with Enduragen grafts. Eight procedures were for spacers in the upper lid, 104 were for spacers in the lower lid, and 17 were for lateral canthal reinforcement. There were 13 eyelid complications, for a complication rate of 10%. Nine cases required surgical revision, and there were four cases of infection, all of which were successfully treated with oral and topical antibiotics. The results of this study are insufficient to adequately evaluate the safety and efficacy of Enduragen. Further research is needed.

Barmettler (2018) published the results of a prospective, randomized clinical trial involving 39 participants (42 eyelids) undergoing lower eyelid retraction repair with spacer graft. Participants were assigned to undergo their procedure with autologous auricular cartilage (n=19 eyelids), SurgiMend (n=11 eyelids), or Enduragen (n=12 eyelids). The authors reported no significant differences between groups with regard to 6-month measures including MRD2, conjunctival injection, tearing, discomfort, itching, corneal abrasions, or repeat procedures.

Fortiva

Fortiva is a product composed of porcine acellular dermal matrix and has been cleared through the FDA’s 510K process. The only currently available published peer-reviewed study addressing its use in a clinical setting was published by Maxwell in 2019, who reported on the results of a retrospective non-randomized controlled study investigating the use of Fortiva (n=72) compared to Strattice (n=98) and AlloDerm (n=59) in 229 participants undergoing abdominal wall reconstruction. The incidence of recurrence of abdominal wall defect was significantly higher in the AlloDerm group (20.3%) compared with the Fortiva (10.2%) and Strattice groups (6.9%) (p=0.040). The 1-, 3-, and 5-year survival rates for the repair with Fortiva were 1.4% and 6.9%, and 0%. For Strattice, the results were 5.1%, 9.2%, and 10.2%, and for AlloDerm, 6.8%, 18.5%, and 20.3%. Although participants in the AlloDerm group had the longest median hernia-free interval, 26.8 months (2-60 months), this was not found to be significantly different from Fortiva and Strattice (data not provided). The most common complication was surgical site infection (26.2%), followed by delayed healing (24.0%). Seroma formation was reported to have been significantly lower in the Fortiva group vs. the Strattice and AlloDerm groups (1.4% vs 13.3% vs 11.9%; p=0.021). This study indicates promising results; however, this data is limited and not methodologically robust. Additional investigation into the safety and efficacy of Fortiva is needed.

GalaFLEX

GalaFLEX is a synthetic bioabsorbable product composed of poly-4-hydroxybutyrate and was cleared through the FDA’s 510K process. In reconstructive surgery GalaFLEX has been used as an alternative to ADM or in combination with ADM both in delayed and immediate reconstruction.

Adams (2018) published a case series report involving 62 participants undergoing mastopexy procedures. The authors reported that 89.7% of participants had successful ptosis correction and maintenance at 1 year. Both participant and surgeon satisfaction for breast shape, droop/sag of the breast, and maintenance of results at 1 year was reported as high. Adverse events deemed to be related to the device occurred in 5 participants (8.0%), including nerve pain, breast swelling, ptosis, and 2 instances of asymmetry. It is not clear how the safety and efficacy of this product compares to other products, including those considered the standard of care for breast procedures. Additional comparative trials are warranted.

Sigalove and colleagues (2023) reported a retrospective case series of 263 individuals (499 breasts) who had immediate, two-stage expander-implant, prepectoral breast reconstruction that compared GalaFLEX plus AlloDerm combination (n=135/250 breasts) to AlloDerm only (n=128/249 breasts). In the GalaFLEX plus AlloDerm group the lower third of the expander was covered by the AlloDerm and the rest of the expander was covered by GalaFLEX Complications after reconstruction were compared between the groups. Mean BMI, preoperative chemotherapy use, skin reducing mastectomy, and bilateral reconstructions were higher in the AlloDerm only group, whereas nipple-sparing mastectomy and unilateral reconstructions were higher in the GalaFLEX plus AlloDerm group. Individuals in the AlloDerm-only group were followed up for an average of 41.9 months, whereas those in the GalaFLEX plus AlloDerm group were followed for an average of 15 months from the date of initial surgery (p<0.0001). Complications occurred in 19 breasts that received AlloDerm-only and 16 breasts that received GalaFLEX plus AlloDerm; overall complication rates were 7.6% and 6.4%, respectively. All complications occurred within the first year after initial surgery; 61% of individuals in the GalaFLEX plus AlloDerm group had at least 1 year of follow-up, and 17% had at least 2 years of follow-up. The rate of complication was 7.6% in the AlloDerm-only group and 6.4% in the GalaFLEX plus AlloDerm group. The rate of infection, major skin necrosis, seroma, capsular contracture, prosthesis exposure/extrusion, and prosthesis loss were less than or equal to 3.0% in the GalaFLEX plus AlloDerm group and did not differ significantly from those in the AlloDerm-only group. There were no significant differences in complications between the two groups with the exception of skin necrosis (5.2% for the AlloDerm-only group vs. 1.2% for the GalaFLEX plus AlloDerm group), which the authors noted was driven by a higher rate of intermediate skin necrosis. However, the rate of major skin necrosis did not differ significantly between the groups. The study is limited by its retrospective nature and the relatively short follow-up duration. The authors concluded that the GalaFLEX has a comparable safety profile, however additional long-term data and clinical experience are needed to comprehensively understand the safety profile of GalaFLEX bioabsorbable matrix for use in breast reconstruction.

Gentrix

Gentrix is a product composed of porcine acellular urinary bladder and has been cleared through the FDA’s 510K process. The only currently available published peer-reviewed study addressing its use in a clinical setting was published by Wang and others in 2018. They reported on a unrandomized controlled trial involving 65 participants who underwent paraesophageal hernia (PEH) repair with (n=32) or without (n=33) reinforcement with Gentrix. There was no difference reported between groups with regard to recurrence rates, size of recurrence, postoperative symptomatic or quality of life improvement. The authors noted that participants in the unreinforced group who suffered recurrence had more severe symptoms and a higher rate of dissatisfaction. Of the 3 participants with recurrences after Gentrix placement, reoperation demonstrated anterior failure where no reinforcement had occurred because of the posteriorly placed U-shaped graft. It is not clear how the safety and efficacy of this product compares to other products, including those considered the standard of care. Additional comparative trials are warranted.

Gore BioA

Gore BioA is a completely synthetic, bioabsorbable product composed of 67% polyglycolic acid and 33% trimethyl chitosan and was cleared through the FDA’s 510K process. Ommer and others published the results of a case series study involving 50 participants with trans-sphincteric (n=28) or supra-sphincteric (n=12) anal fistula who were treated with Gore BioA (2012). Postoperatively, 1 participant developed an abscess which had to be managed surgically. In 2 participants, the plug had fallen out within 2 weeks after surgery. Six months after surgery, the fistula had been healed in 20 participants (50.0%). Three additional fistulas healed after an additional 7 to 12 months. The authors reported that the overall healing rate was 57.5% (23/40). However, they noted that healing rates differ significantly between the surgeons (from 0 to 75%), and also varied depending on the number of previous interventions. In individuals having had only drainage of the abscess, success occurred in 63.6% (14/22) whereas, in those having had one or more flap fistula reconstructions, the healing rate decreased slightly to 50% (9/18). Further study is warranted to better understand the impact of surgeon experience as well as optimal selection criteria for individuals requiring treatment for anal fistulas. Heydari (2013) described the results of a retrospective case series study involving 48 participants with 49 anal fistulas treated with the Gore BioA. The overall healing rate was reported to be 69.3% (34/49 fistulas, 33/48 participants). Eight participants (24.2%) had complete healing by 3 months after surgery, 21 participants (63.6%) had healed by 6 months, and 4 participants (12.1%) had healed by 12 months. At 3 months, there were no reports of perineal pain or fecal incontinence. The authors reported no incidents of dislodged devices, anal stenosis, bleeding, or local infection.

In 2018 Jordan and others published the results of a retrospective comparative study involving 87 participants undergoing breast reconstruction with mesh underlay reinforcement at 123 sites with either polypropylene mesh (n=58) or Gore BioA (n=65). The overall incidence of bulge or hernia was 11.4%. The Gore BioA group experienced significantly more bulges/hernias than the polypropylene mesh group (20% vs. 1.7%). They concluded that use of Gore BioA was associated with a 13.3-fold risk of bulge/hernia (p=0.016) and was not appropriate for anterior rectus fascia reinforcement following abdominal tissue transfer.

While these reports are promising, the lack of larger comparative trials impedes a full assessment of the efficacy of the GORE BioA device. Further investigation is warranted.

In 2017, the American Society of Colon and Rectal surgeons published a new Practice guideline for the management of anal fissures (Stewart, 2017). Their recommendations do not mention the use of grafts or plugs of any kind.

Gore Acuseal Cardiovascular Patch

Gore Acuseal Cardiovascular Patch is an expanded polytetrafluoroethylene (ePTFE) separated by an elastomeric layer and may be available both with and without covalently bound bioactive heparin. It has been cleared through the FDA’s 510K process. Stone (2014) published the results of a prospective randomized study comparing clinical outcomes of Acuseal vs. bovine pericardium patching (Vascu-Guard) when used for primary closure for carotid endarterectomy. This study involved 200 participants assigned in a 1:1 fashion and the mean follow-up period was 15 months. They reported that mean hemostasis time was 4.90 min for Acuseal vs. 3.09 min for Vascu-Guard (p=0.027). The mean operative times were similar for both groups (2.09 hr vs. 2.16 hr, p=0.669). The incidence of reexploration for neck hematoma was higher in the Vascu-Guard group; 6.12% vs. 1.03% (p=0.1183). The incidence of perioperative ipsilateral neurologic events was 3.09% for Acuseal patching vs. 1.02% for Vascu-Guard patching (p=0.368). The respective freedom from ≥ 70% carotid restenosis at 1, 2, and 3 years were 100%, 100%, and 100% for ACUSEAL patching vs. 100%, 98%, and 98% for Vascu-Guard patching (p=0.2478).

AbuRahma (2023) reported on the 10-year results of the study previously published by Stone et al. (2016). Mean follow-up time was 81 months (range 0-149 months). No significant differences were reported between groups for rates of long-term death, 47% in the Acuseal group vs. 48% in the Vascu-Guard group p=0.9402). Similarly, the incidence of late strokes was reported to be 5% in both groups (p=1.0). One patch complication was noted in the Acuseal group (infection) vs. the Vascu-Guard group (aneurysmal dilatation and rupture, no p-values provided). No significant differences in the rate of reintervention was reported (5% in the Acuseal group vs. 4% in the Vascu-Guard group, no p-values provided). The rate of ≥50% restenosis was 9% for the Acuseal group vs. 22% for Vascu-Guard group (p=0.0186). The rates of ≥80% restenosis, freedom from stroke, freedom from stroke/death, freedom from ≥80% restenosis, and overall survival rates were all not significantly different between groups for any time point (p=0.564, p=0.1112, p=0.8591, p=0.9407, p=0.9123, respectively). The authors concluded that both product are durable and have similar clinical outcomes at 10 years, except that ACUSEAL patching has significantly better rates of freedom from ≥50% restenosis.

While this data is promising, it compares does not compare outcomes to standard care, which is the critical question with regard to these products. Further investigation is needed to elucidate that issue.

Grafix CORE

Grafix CORE is a grafting product derived from allogeneic chorion membrane. It is treated as human tissue for transplantation under the FDA’s HCT/P process.

Frykberg (2016) reported the results of a prospective case series study involving participants with complex DFUs ≤ 15 cm in their longest dimension and extending through the dermis with exposed muscle, tendon, fascia, bone, or joint capsule. All were treated with weekly applications of Grafix CORE. The intent-to-treat (ITT) population included 31 participants and the per-protocol population included 27 participants. The ITT participant population had significant co-morbidities, with 80% having hypertension, 60% current or former smokers, 55% having heart disease, and 45% having a previous partial foot amputation. Prior advanced treatment (for example, negative pressure wound therapy) for the index wound had occurred in 67.7% of participants. At 16 weeks, 96.3% of the per-protocol group had 100% granulation of the index wound and complete closure occurred in 59.3%. The mean area reduction of the index wound at day 28 was 54.3% and 72.8% at 8 weeks. At the end of the 16-week study period the mean wound area reduction was 92.3%. No Grafix-related adverse events were reported. This study demonstrated the use of Grafix CORE in the healing of complex DFUs. However, the small study population and lack of controls hampers the generalizability of these results.

Raspovic (2018) reported a retrospective case series analysis of 360 participants with 441 DFUs treated with Grafix PRIME or Grafix CORE using data from Net Health’s Wound Expert electronic health records database. The mean size of the index wound was 5.1 cm² with 3.9 mm depth. Mean wound duration prior to study treatment was 102 days. The mean duration of treatment with a Grafix product was 89.3 days (median 56.0). Complete wound closure at the end of treatment occurred in 59.4% of participants. Median time to closure was 42.0 days with a median of 4 graft applications. The proportion of closure decreased as wound size increased, with 72.3% of wounds between 0.25 cm² to 2 cm² having complete healing at a median of 21 days and 4 applications. For wounds larger than 25 cm², only 27.8% achieved complete healing at a median of 105 days and 11 applications. The authors did not provide any data regarding the percentage of participants receiving treatment with Grafix PRIME vs. those receiving Grafix CORE.

At this time, the safety and efficacy of Grafix CORE, is uncertain. Additional well designed and conducted trials are warranted.

Helicoll

Helicoll (Encoll Corp., Freemont, CA) is a bioengineered high purity Type-I collagen cleared under the FDA 510(k) process. A randomized controlled clinical trial by Narayan (2024) enrolled 28 individuals with DFUs and compared Helicoll to an unspecified dehydrated human amnion and chorion membrane product over 4 weeks. The study showed that 85.71% (12/14) of participants in the Helicoll group achieved at least a 50% reduction in DFU size, compared to 50% (7/14) in the dehydrated membrane group (p=0.245). Complete closure was observed in 10 and 7 participants, respectively. The Helicoll group demonstrated a mean DFU size reduction of 86.48%, while the dehydrated membrane group recorded 77.70%. The authors noted that their statistical analysis indicated a significant difference in mean wound reduction rates (93.62 ± 0.12% vs. 77.71 ± 0.28%, p=0.05), suggesting enhanced wound-healing capabilities for Helicoll in managing DFU. However, based on the limited sample size, short follow-up time, and unspecified nature of the comparator, the results of this study are not generalizable.

Hyalomatrix

Hyalomatrix is a synthetic wound covering product composed of a benzyl ester of hyaluronic acid. This product has been approved through the FDA’s PMA process. The currently available evidence addressing the use of Hyalomatrix is limited mostly to uncontrolled, unblinded case series studies. Only one RCT has been published to date involving 16 participants with VSUs, 9 of which were treated with Hylaomatrix and 7 treated with standard wound care (Alvarez, 2017). The authors reported that the incidence of wound healing at 12 weeks was 66.6% for the Hyalomatrix group vs. 14.2% for controls (p=0.066). At 16 weeks, the incidence of wound healing was 87.5% of participants in the Hyalomatrix group vs. 42.8% in the control group (p=0.059). The mean time to healing in the Hyalomatrix group was 41 days compared with 104 days in the control (p=0.029). The largest studies available involve 300, 262, 79, and 57 participants (Gravante, 2007; Caravaggi, 2003 and 2011; Gravante 2010, respectively). The Carravaggi study addresses chronic wounds while the Gravante studies address burns. The rest of the studies published involve significantly fewer than 30 participants and encompass a variety of indications including various surgically created wounds (Faga, 2013; Landi, 2014; Onesti, 2014), traumatic wounds (Kozusko, 2023; Onesti, 2014; Vaienti, 2013), and chronic ulcers (Motolese, 2013).

In summary, the body of literature addressing Hyalomatrix is limited to predominantly case series studies involving a heterogeneous collection of indications. While most of these studies demonstrate promising results, the uncontrolled, unblinded nature of these studies does not allow proper assessment of the safety and efficacy this product.

Integra Flowable Wound Matrix

In 2017, Campitiello and colleagues published an RCT comparing Integra Flowable Wound Matrix vs. standard care for the treatment of 46 participants with DFUs with irregular geometries. There were 23 participants in each group who were evaluated once a week for 6 weeks. The authors reported that the overall complete healing rate was 69.56%, with the rate in the Integra group being 86.95% vs. 52.17% in the control group (OR=1.67, p=0.001). Mean time to healing was 29.73 days in the Integra group vs. 42.78 in the control group (p<0.000). The amputation and rehospitalization rates in the Integra group were 4.34% vs. 30.43% in controls (RR=0.16, p=0.028). The authors concluded that Integra Flowable Wound Matrix was significantly superior to the wet dressing, but that additional research will shed more light on the promising advantages of this material in healing diabetic foot ulcers.

Keramatrix

This product is composed of freeze-dried acellular animal-derived keratin and has been approved through the FDA’s 510K process. At this time, the most rigorous evidence is a nonrandomized controlled study involving 40 participants with superficial or partial thickness burn injuries treated with Keramatrix, compared to 40 historical controls who received standard of care treatment (Loan, 2016). The results indicated a significantly faster mean healing time in the Keramatrix group vs. controls (8.7 days vs. 14.4 days, p<0.05), hospital inpatient days (0 days vs. 2.6 days, p<0.05), and number of outpatient appointments following initial therapy (1.2 vs. 3.3, p<0.05). No differences in complications were reported.

KeraSys

Kerasys is composed of decellularized xenogeneic porcine small intestinal submucosa and has been approved through the FDA’s 510K process. The only available study described in the published peer-reviewed literature addressing the use of this product was published by Nagi and others in 2013. Their study was a retrospective, noncomparative, consecutive case series of 42 eyes with tube-related exposure complications due to glaucoma drainage device surgery. KeraSys was used to cover the defect. The authors reported that 4 (10%) eyes experienced patch-related complications. Two had exposure at 8 months postoperatively, 1 had exposure at 13 months postoperatively, and 1 with exposure at 4 weeks postoperatively. They concluded that, “The effectiveness of the KeraSys patch graft is limited by the higher than expected early exposure rate found in this case series.”

MatrACELL

MatrACELL is a decellularized allograft product composed of human cardiovascular tissue treated as human tissue for transplantation under the FDA’s HCT/P process.

Currently the only study published regarding the use of this product was published by Hopkins (2014). This nonrandomized controlled study involved 108 consecutive participants undergoing cardiovascular reconstructive procedures using MatrACELL pulmonary artery patches during pulmonary arterioplasty. A second retrospective cohort of 100 participants who received arterioplasty patches using classical cryopreserved pulmonary artery allografts (n=59 participants) or synthetic materials (n=41 participants) was used for comparison. The reported results included that 106 participants with 118 decellularized patches had no device-related serious adverse events, no device failures, and no evidence of calcifications on chest roentgenograms. In contrast, the control participants experienced an overall 14.0% patch failure rate requiring device-related reoperations (p<0.0001) at mean duration of 194 ± 104 days (range, 25 to 477 days). The authors concluded that the intermediate-term data obtained in this study suggest favorable performance by decellularized pulmonary artery patches, with no material failures or reoperations provoked by device failure.

Additional study is warranted to fully evaluate the safety and efficacy of this product.

MatriDerm

MatriDerm is a decellularized dermis allograft product treated as human tissue for transplantation under the FDA’s HCT/P process. Riml (2011) reported a study of 30 participants undergoing nasal tip skin grafts non-randomly assigned to receive either conventional FTSG, retroauricular perichondrodermal composite grafts, or skin transplantation supplemented with MatriDerm. Ten participants were assigned to each group. This retrospective study was conducted in a randomized and blinded manner by assigned reviewers using the Manchester scale. The authors report that 2 (20%) of the MatriDerm participants developed fistulae and concluded that MatriDerm was not suitable for nasal tip reconstruction.

Another study by Haslik and colleagues evaluated the use of MatriDerm for the management of FTSG (2010). This case series study involved 17 participants with upper extremity skin wounds, all of whom received MatriDerm in conjunction with unmeshed skin grafts. The reported take rate was 96%. A 12-month follow-up Vancouver scale score of 1.7 and DASH (disability of arm-shoulder-hand) score showed excellent hand function in participants with burn injury and participants with a defect due to the harvest of a radial forearm flap achieved satisfying hand function.

Wallner and colleagues (2023) published a retrospective study that compared the use of single autologous STSG alone or in combination with MatriDerm ADM in 147 cases of severe traumatic soft tissue defects of the leg with exposed structures, such as tendons, ligaments, vessels, or bone of the lower extremities. Severe soft tissue defects consisted of 18 open fractures with extensive decollement, 43 thermic and chemical burns, 78 severe soft tissue lesions, and 8 ulcers. Overall, soft tissue defects were more severe in the MatriDerm plus STSG group. The healing rate, defined as the number of individuals with take rate ≥ 75%, was 88/147 (60%) and no significant differences between the groups was reported (p=0.15). Despite variable wound complexity between the groups there were no differences in scar tissue quality 12 months postoperatively. Overall complication rate was approximately 25%. In 15% of the cases, a surgical revision was required. The number of cases with at least one necessary surgical revision was 4 in the STSG-only group compared to 18 in the MatriDerm plus STSG group (p=0.02). The number of individuals with documented adverse events (33%) or necessary revision surgery (21%) was higher in the STSG plus MatriDerm group. The complications reported after more than 100 days included scar instability, fistula formation, and swelling. Additionally, the use of negative pressure wound therapy may have impacted the STSG take rate. The authors concluded that surgical treatment with STSG and additional MatriDerm application is a satisfactory alternative for dermis replacement in individuals with severe skin defects, independent of age. Due to the higher rate of adverse events, complications, and surgical revision, further studies with larger, well designed trials are needed to fully evaluate the safety and efficacy of MatriDerm..

In a retrospective single-center original article, Do (2024) evaluated 12 individuals who underwent maxillectomy for oral cancer treated with a combination of MatriDerm® and (Neoveil.) Over a follow-up ranging from 2 to 20 months, 41.7% of participants experienced fistula formation, but no surgical revisions were required. The incidence of fistulas depended on tumor stage, bone invasion, defect dimensions, and sinus mucosa preservation (p<0.05), rather than product-specific performance. None of the participants developed mouth-opening limitations, indicating potential benefits of the combined technique. However, since this study combined Matriderm and Neoveil in all participants, the relative benefits of each product alone cannot be determined and further research is needed.

MediHoney

The use of honey has been proposed for the treatment of various skin conditions including burns, chronic ulcers, and superficial abrasions. It has been hypothesized that honey, with its antibacterial properties, can significantly improve skin healing when applied topically to skin wounds. Several randomized controlled trials have been published involving MediHoney, a product cleared through the FDA’s 510K process, most addressing the treatment of venous leg and foot ulcers. Jull and colleagues published the largest of these trials, which included 368 participants randomized to receive treatment with either calcium alginate dressing impregnated with manuka honey or standard care with whatever dressings were appropriate for the individual at that time (2008). After following the participants for a total of 12 weeks of follow-up, the authors concluded that there was no significant difference in outcomes between the two groups. It was noted that the honey-treated group experienced significantly greater numbers of adverse events (p=0.013). Contradicting these findings is a study by Gethin and Cowman (2008). In this study, 108 participants with venous ulcers were randomized to receive treatment with either honey dressing or standard hydrogel therapy. The findings were that the honey-treated group had significantly better results in terms of median reduction in wound size at 12 weeks (44% vs. 33%, p=0.037), but no significant differences between groups in other primary endpoints were reported.

The other most studied condition addressed in the literature is the treatment of burns. The largest study currently available addressing burns involved 150 participants randomized to receive treatment with either silver sulphadiazine (SSD) or honey (Malik, 2010). Each participant functioned as his or her own control, with one burn site randomly treated with SSD and the other with honey. The authors report that the honey-treated sites had significantly faster re-epithelialization and healing of superficial and partial thickness burns than the SSD sites (13.47 days vs. 15.62 days, p<0.0001). Additionally, the honey-treated sites achieved complete healing significantly faster than SSD sites (21 days vs. 24 days, p<0.0001).

Lund and colleagues compared the use of honey-coated dressing for breast malignant wounds. In this study, 67 participants, 79% of whom had breast cancer, were randomized to receive treatment with either honey-coated dressing (n=34) or silver dressing (n=33). The authors report no significant differences between groups, and they concluded that the possible antibacterial effect of either treatment “could not be confirmed in these malignant wounds.”

At this time, the evidence addressing the use of honey for skin wounds is lacking. The current studies are mostly unblinded, controlled studies, and a large variety of controls have been used. These factors make comparison study outcomes difficult to interpret. Further investigation with large well-done blinded trials using standardized controls is warranted.

MegaDerm

MegaDerm Plus (L & C Bio, Seoul, Korea) is a suite of products (MegaDerm Plus, MegaDerm HD, MegaFill, MegaSheet) made from acellularized human skin-derived acellular dermal matrix (ADM) allograft, and is regulated through the FDA’s HCT/P process as human tissue for transplantation. The products are used in reconstructive and aesthetic surgery to promote healing and reduce scar tissue by becoming incorporated into the surrounding tissue and gradually replacing the individual’s own collagen. MegaDerm Plus^® is FDA approved in Korea through the HTC/P process for breast, burr hole, and endopthalmic procedures. However, the FDA has not approved MegaDerm or any other ADM for use in breast reconstruction.

In 2012 Kim reported on a prospective non-randomized study investigating the use of MegaDerm in parotidectomy procedures involving 109 participants who underwent treatment with Megaderm (n=58) or no implant (n=51). Decision on what group the participants were allotted was made by the participant in consultation with the surgeon. The study initially enrolled 134 participants but 25 were lost to follow-up. The authors reported a significantly higher rate of seroma at postoperative week 1 in the Megaderm™ group compared to the control group (14 vs. 6, respectively, p=0.22). However, no significant differences between groups were reported with regard to other complications, including infection (p=1.0), Hematoma (p=0.182), skin necrosis (p=1.0), and pain (p=0.28). Additionally, no difference between groups were reported with regard to patient-reported Frey’s syndrome quality scores at 3, 6, and 12 months. However, incidence of Frey’s syndrome was significantly higher in the MegaDerm group at 3, 6 but not 12 months (p=0.32, 0.037 and 0.28, respectively). The authors stated that use of MegaDerm for parotidectomy procedures, however, the higher rate of seroma is of concern and should be further evaluated in studies with less potential for selection bias.

In 2017, Kim and colleagues retrospectively assessed 73 individuals to determine whether Megaderm (n=29) could replace absorbable mesh (n=22) or porous polyethylene (n=22) in orbital wall reconstruction. Enophthalmos, range of eyeball movement, diplopia, and infraorbital nerve numbness were evaluated at 1 and 3 weeks, and 3 and 6 months. At 6 months, complete resolution of all of these measures was reported in all groups (p=1.0). The most common complication was transient and self-limited diplopia, which developed in the early postoperative stage, one in the mesh group and 2 in the polyethylene group. No MegaDerm group participants developed diplopia. Infraorbital numbness was observed in 1 mesh group participant and 1 polyethylene group participant. Transient and self-limited lagophthalmos was reported in 1 mesh group participant. No p-value was provided for these intergroup comparisons. The authors concluded that MegaDerm, based on the results of this study, would be an excellent alternative material for orbital wall reconstruction. However, additional research is needed to verify these findings in a more robust trial.

Park (2023) retrospectively compared freeze-dried Megaderm to pre-hydrated Megaderm in 78 individuals undergoing immediate implant-based breast reconstruction with latissimus dorsi muscle coverage. The freeze-dried form was used in 26 individuals, while 52 individuals received the pre-hydrated product. The overall complication rate did not differ significantly, 30.8% in the freeze-dried group compared to 55.8% in the pre-hydrated group (no p-value provided). Seroma was more frequent in the pre-hydrated ADM group (n=20 vs 4) but the difference between the two groups was not statistically significant (p=0.120). The pre-hydrated version showed a higher mean shape score of 3.46 plus or minus 0.5 compared to 3.08 plus or minus 0.7 in the freeze-dried cohort (p=0.019). The authors concluded that while complication rates were similar between pre-hydrated ADM and freeze-dried ADM, aesthetic outcome was better in pre-hydrated ADM in terms of symmetry. Further investigation into the use of MegaDerm and its variants are needed to better understand the clinical utility of this product.

In a single-blind, randomized, controlled trial published in 2024, Han and colleagues evaluated 56 individuals undergoing immediate prepectoral direct-to-implant breast reconstruction using Megaderm™ with and without a basement membrane. Specifically, 30 participants received Megaderm HD (with basement membrane) and 26 participants received Megaderm Flex HD (without basement membrane). The total drainage volume was 893 milliliters plus or minus 399 in the Megaderm HD group compared to 859 milliliters plus or minus 341 in the Megaderm Flex HD group (p=0.74). Drains were removed at approximately 17 to 18 days. No significant differences between groups were observed in terms of overall complication rates between the 2 groups (26.7 vs. 23.1, respectively, p=0.76), the rate of seromas (3 vs. 0, respectively, p=0.09),infection (1 vs. 0, respectively, p=0.35), wound dehiscence (2 vs. 3, respectively, p=0.52), mastectomy flap necrosis (0 vs. 1, respectively, p=0.28), or capsular contracture (3 vs. 2, respectively, p=0.76). The authors concluded that Megaderm Flex HD in implant-based breast reconstruction was safe.

Overall, the available evidence regarding the use of MegaDerm is promising for a variety of indications. However, additional research in more rigorous studies is needed to be able to generalize the conclusions of the studies available to date.

Menaflex (formerly “Collagen meniscus implant” or CMI)

Collagen meniscus implants (e.g., Menaflex) have been proposed as a treatment method for individuals with a damaged knee meniscus. Menaflex is a human-derived acellular collagen product treated as human tissue for transplantation under the FDA’s HCT/P process. At this time, there is only one large trial for this type of procedure (Rodkey, 2008). This study involved 311 participants with irreparable injury of the medial meniscus or a previous partial medial meniscectomy. The study population was divided into two groups, those with prior meniscal surgery (chronic group) and those with no prior surgery (acute group). These populations were further randomized to receive either treatment with a collagen meniscus implant or a partial meniscectomy only. The mean duration of follow-up was 59 months (range, 16 to 92 months). Repeat arthroscopies done in the experimental group at 1 year showed significantly (p=0.001) increased meniscal tissue compared with that seen after the original index surgery. In the chronic group, participants who had received the collagen implant regained a significantly higher degree of pre-surgery activity than did the controls (p=0.02). This group also underwent significantly fewer non-protocol reoperations (p=0.04). The authors reported no significant differences between the two treatment groups in the acute arm of the study.

Zaffahnini and colleagues conducted a long-term trial of the performance of the Menaflex implant in 33 participants. This nonrandomized controlled trial allowed participants to choose treatment with either Menaflex (n=17) or partial medial meniscectomy (n=16). Participants were evaluated at baseline, 5 years and then 10 years after surgery. At 10 years, the authors report that the Menaflex group showed significant improvement compared to meniscectomy with regard to visual analog scale for pain (p=0.004), International Knee Documentation Committee knee form (p=0.0001), Teger index (p=0.026), SF-36 Physical Health Index (p=0.026), and SF-36 Mental Health Index (p=0.004). Radiographic evaluation showed significantly less medial joint space narrowing in the Menaflex group than in controls (p=0.0003). There were no significant differences reported between groups regarding Lysholm score (p=0.062) and Yulish score (p=0.122). Genovese score remained constant between 5 and 10 years after surgery (p=0.5).

Another case series study of 22 participants followed for 10 years was reported by Monllau and colleagues (2011). The results of this study demonstrated that several measures improved, including the visual analog pain scale and radiographic joint line narrowing. The Lysholm score was significantly improved, from 59.9 at baseline, 89.6 at 1 year (p<0.001), and 87.5 at 10 years (p<0.001). Failure rate was only reported to be 8% in the 25 participants initially implanted.

Van Der Straeten published the results of a cohort study of 313 participants who received treatment with the collagen meniscal implant and were followed for a mean follow-up of 6.8 years (2016). A total of 56.5% of the implants were still intact and in place; 27.4% had been removed. This included 63 implants converted to a knee arthroplasty (19.2%). The overall cumulative allograft survivorship was 15.1% at 24.0 years. Simultaneous osteotomy significantly deteriorated survival (0% at 24.0 years) (p=0.010). The authors stated that 61% of participants underwent at least one additional surgery (range 1-11) for clinical symptoms after implantation. They concluded that the collagen meniscal implant did not delay or prevent tibiofemoral OA progression.

Another large cohort study was reported by Waterman (2016). This study involved 230 active-duty military personnel who underwent treatment with the collagen meniscal implant. A total of 51 complications occurred in 46 (21.1%) participants, including a secondary tear or extrusion (9%). The authors reported that 10 participants (4.4%) required secondary meniscal debridement at a mean of 2.14 years. Revision was done in 1 participant (0.4%) and 20 participants (0.9%) subsequently underwent total knee arthroplasty. After implantation, 50 participants (22%) underwent knee-related military discharge at a mean of 2.49 years postoperatively. They concluded that while there were low reoperation and revision rates, their investigation indicated that 22% of participants who received implants were unable to return to military duty due to persistent knee limitations at short-term follow-up.

While these studies show that there is some potential benefit to the use of meniscal collagen implants in some populations, further data from rigorously designed and conducted trials is warranted to further understand the clinical implications of this technology.

Menaflex was originally cleared by the FDA in the 510K process. Subsequent to further review by the FDA, this clearance was revoked. The manufacturer, ReGen Biologics, Inc. went bankrupt shortly thereafter. The Menaflex device is currently not marketed in the U.S.

Miro3D

Miro3D™ Wound Matrix (Reprise Medical, Plymouth MN) is a porcine liver tissue-derived product cleared through the FDA’s 510(k) process. In a retrospective case series by Abdo (2024), 11 individuals with type 2 diabetes and 13 deep or tunneling foot ulcers present for at least 4 weeks underwent surgical debridement and application of Miro3D. One individual also underwent are with the Miro3D Fibers Wound Matrix product. Over the 4-week study period, 62% (8/13) of ulcers achieved at least 50% area reduction by 4 weeks, and 54% (7/13) closed fully by 12 weeks, with all ulcers ultimately healing in an average of 13.1 weeks (range 2.0–22.3 weeks). Participants with larger initial volumes and poor offloading adherence tended to take longer to heal. However, no new infections, readmissions, or adverse events linked to Miro3D were reported. The concluded that the results suggest that Miro3D Wound Matrix effectively creates a protective environment for managing deep or tunneling DFUs, with early improvements in depth and volume. However, the study’s retrospective design and relatively small sample size and other methodological issues limit broader generalizability, and further research is needed.

Myriad Matrix and Myriad Morcells™

Myriad Matrix is a product composed of processed ovine forestomach matrix and cleared through the FDA’s 510K process. Two studies published in 2023 are the first to address the clinical utility of Myriad Matrix and Myriad Morcells.

Cormican (2023) reported the results of a retrospective pilot case series involving 10 participants with 13 contaminated lower-extremity defects undergoing surgical reconstruction with Myriad Matrix (n=3), Myriad Morcells (n=4), or both (n=6). All participants had at least 1 significant comorbidity with the potential to complicate their healing trajectory. Mean defect age was 3.5±5.6 weeks and mean area was 217.3±77.9 cm². Most defects had exposed structures (85%), and all defects were Centers for Disease Control and Prevention grade 2 or higher. Mean time to 100% granulation tissue formation was 23.4±9.2 days, with a median product application of 1.0. Staged reconstruction was used in 7 of 13 defects, with the remainder (6 of 13) left to heal via secondary intention using standard wound care protocols. Mean follow-up was 7.4±2.4 weeks, with 4 wounds (30%) lost to follow up ≤5 weeks. No major postoperative infections or adverse events were reported. The small sample size, and high loss to follow-up do not allow reasonable, generalizable conclusions regarding the clinical utility of these products

Bosque (2023) described the results of a similar retrospective case series study involving 50 participants with complex lower-extremity defects undergoing surgical reconstruction with Myriad Matrix (n=41), Myriad Morcells (n=3), or both (n=6). The participants had heterogenous etiologies, including diabetic foot ulcers (DFUs) (48%), half of which were complicated by a necrotizing soft-tissue infection (50%). Additionally, in the total population, 34% of participants had exposed bone, 10% had exposed tendon, 18% had both exposed tendon and bone, and 4% had exposed capsule. Ten participants (20%) were lost to follow-up before complete closure of the defect, but after 100% granulation tissue had formed. Where Myriad products were used for dermal regeneration (n=47), the median time to 100% granulation tissue was 17 days (mean, 26±22.2 days; range, 7–120 days). A total of 38 participants (76%) were closed by secondary intention, with an overall median time to close of 14 weeks (mean, 14.0±5.9 weeks; range, 1–27 weeks). The overall time to closure from the initial surgical procedure to closure across defects (n=40) was 13 weeks (mean, 13.7±6.9 days; range, 2–29 weeks). This study involving these two Myriad products is promising, but the results are limited by multiple factors, including significant loss to follow-up, heterogeneity of wound etiologies, and use of multiple versions of the product used.

Overall, additional data from well designed and conducted trials is needed to establish the clinical utility of Myriad Matrix and Myriad Morcells.

NEOVEIL

NEOVEIL Tube/Sheet (Gunze Limited, Kyoto, Japan) is a synthetic surgical mesh made from bioabsorbable polyglycolic acid (PGA), designed for use in surgical procedures that require reinforcement of soft tissue transection or resection with staples or sutures. It is applicable in various surgeries, including lung and liver resections, as well as bronchial, bariatric, colorectal, and gastrointestinal procedures. NEOVEIL has received clearance under the FDA 510K process.

Neuragen

Neuragen collagen tube conduits are composed of bovine-derived acellular collagen and have been cleared through the FDA’s 510K process. This product is proposed for use in peripheral nerve repair.

In a unblinded RCT of Neuragen 44 participants with ulnar or median nerve lacerations were assigned to treatment with Neuragen (n=23) vs. direct fascicular repair or nerve grafting (n=21) (Boeckstyns, 2013). The authors reported that data for only 36 participants (81%) were available at the 24-month follow-up visit. However, they do not provide information regarding which groups the dropouts were from. At 24 months no significant differences between groups were reported with regard to amplitudes, latencies and conduction velocities. With regard to comparison to the contralateral hand, both groups remained significantly deficient on all electrophysiological measures. No surgical complications were reported. These results may indicate some benefit from the use of Neuragen, but the generalizability is hampered by missing information regarding participants at 24 months, as well as methodological flaws such small study population and lack of blinding.

In addition to this study, several unblinded non-randomized controlled trials and multiple case series studies addressing the use of Neuragen have been published, with most involving small numbers of participants (Ashley, 2006; Bushnell; Distinct, 2013; Erakat 2013; Farole, 2008; Haug 2013; Huber 2017; Karup, 2017; Lohmeyer, 2014; Rbia, 2019; Schmauss 2014; Taras, 2011; Wangensteen, 2010; Wilson, 2016). These studies do not adequately control for bias and the clinical utility and generalizability of their conclusions is limited.

Subsequently, Ilyas (2024) reported a multicenter US based RCT that included 220 participants with digital nerve injuries, treated either with type I bovine collagen conduit (CONDUIT) or a PNA. The CONDUIT group used the NeuraGen Nerve Guide, whereas the PNA group used the Avance Nerve Graft. Inclusion criteria were individuals 18- to 69-years with 5 to 25 mm digital nerve gaps within 24 weeks of injury. Participants were randomized (1:1) to PNA or CONDUIT repairs. Cold Intolerance Symptom Severity (CISS) scores and sensory function testers were assessed at first visit (FPV), 1-, 3-, 6-, 9-, and 12-months post-surgery, both participants and assessors blinded to treatment. One hundred eighty-three participants completed the last evaluable visit (LEV) of 6 months or more of follow-up; of these, 91 received PNA repair and 92 had CONDUIT repair. No significant differences were observed in demographics, gap length, time to repair, or injury mechanism between the groups. The average gap lengths were 13.6 mm for the PNA group and 13.0 mm for the CONDUIT group. The average time to repair was 28.2 and 23.4 days for repairs, respectively. Both groups reported a reduction in the CISS over time, indicative of improved cold intolerance symptoms. The mean CISS score for the entire cohort decreased from 31.15 ± 29.25 at FPV to 23.42 ± 22.16 at the LEV. The reduction in CISS score was numerically greater but not statistically different in the PNA group (10.39 points) compared with the CONDUIT group (5.23 points). A sub-analysis showed more participants improved from severe/extremely severe cold intolerance to mild cold intolerance for PNA compared with CONDUIT at 1 month and LEV (p< 0.05). The CISS scores also correlated with sensory function testing. The authors concluded that PNA had improved cold tolerance outcomes for participants with more severe cold intolerance at FPV relative to nerves repaired with CONDUIT. The study was limited by loss to follow-up at later timepoints in the study. At the 1-month timepoint, the study had a total of 178 participants, but by 12 months, only 149 were available for evaluation. Target follow-up for the study was 12 months, however, participants were assessed at or greater than 6 months, which included up to 15 months out from repair. The study did not include a sub-analysis of participants who concomitantly underwent vascular repair. This was due to a low overall number of participants with vascular injury requiring repair, which is likely a result of the exclusion criteria of the study as well as study design limitations. This limits the generalizability of this study to patients with nerve injuries who do not require vascular repair.

Further study is needed in the form of larger, well-designed trials to fully evaluate the safety and efficacy of this product.

Neuro-Patch

Neuro-Patch™ (B. Braun Medical Inc., Bethlehem, PA) is a synthetic dura mater substitute composed of fine-fibered microporous polyester urethane fleece, cleared through the FDA’s 510(k) process. A non-randomized comparative study was published by Wales (2024), involving 11 participants, (6 who prospectively received treatment with Neuro-Patch and 5 retrospective participants treated with autologous grafts). In the Neuro-Patch group, the authors reported no cerebrospinal fluid leaks, need for lumbar drains, or hearing loss by the 6 month follow-up. Discharge occurred within 48 hours in all participants in this group, with no readmissions. By contrast, the control group had a higher rate of complications, including two instances of CSF leak with lumbar drains placement. They reported an average inpatient stay or 91.2 hours (range: 48–120 h), with three participants having stays of 5 days. Although these findings suggest Neuro-Patch may be promising for large middle fossa dural defect repair, further high-quality research with larger, more diverse populations and extended follow-up is warranted.

NeuraWrap

NeuraWrap nerve wrap is a product composed of bovine-derived acellular collagen and glycosaminoglycan and has been cleared through the FDA’s 510K process. This product is proposed for use in peripheral nerve repair.

At this time, the available peer-reviewed published data addressing the clinical utility of NeuraWrap is limited to a small number of studies (Hibner, 2012; Kokkalis, 2016; Soltani, 2014). Additional evidence addressing the clinical utility of this product from large, well-designed, and conducted trials is needed to fully assess the clinical utility of this product.

Novosorb Biodegradable Temporizing Matrix (BMT)

Novosorb Biodegradable Temporizing Matrix (BMT) product is composed of porous biodegradable polyurethane foam and has been cleared through the FDA’s 510K process. This product has been proposed for the treatment of various dermal conditions including burns, ulcers, chronic wounds, etc.

At this time there is a reasonable number of studies published in the medical literature addressing the use of Novosorb for a variety of conditions including burns, treatment of necrotizing fasciitis, DFUs, and chronic complex wounds (Solanki, 2020; Schlottmann, 2022; Li, 2021; Lo, 2022; Austin, 2023; Kidd, 2023; Lo, 2023; Betar, 2023; and Guerrico, 2023). However, due to several factors, including a nongeneralizable sample and other factors, the results cannot be generalized to the wider population. Larger studies in the form of well-designed and conducted trials are needed to assess the clinical utility and efficacy of Novosorb.

Ologen Collagen Matrix

Ologen Collagen Matrix product is composed of acellular porcine intestine and has been cleared through the FDA’s 510K process. The use of this product has been proposed for a variety of ophthalmological indications; however, the published literature has been limited. The most rigorous trial to date was an open label, non‑randomized, prospective study involving 93 participants undergoing phacotrabeculectomy assigned to receive treatment with mitomycin C (n=53) or Ologen (n=40). The authors reported that after 12 months follow-up there were no significant differences between groups with regard to best corrected visual acuity (p=0.151), intraocular pressure (p=0.254), mean number of medications used (p=0.91) or overall procedure success (p=0.745). No reported repeat procedures, blebitis or endophthalmitis were reported. This study indicates equal outcomes from the use of mitmycin C vs. Ologen during phacotrabeculectomy. However, the study was not designed as a non-inferiority trial and contained several methodological flaws that limit the generalizability of the reported findings. Further investigation in the form of well-designed and conducted studies is needed.

Park (2022) published a retrospective analysis of 72 individuals with glaucoma who underwent XEN gel stent implantation with (n=42) and without (n=30) Ologen collagen matrix augmentation. Surgical success, defined as intraocular pressure (IOP) reduction greater than 20% than preoperative IOP, and the percentage of postoperative complications were compared between the Ologen implant augmented group and the non-augmented group. The surgical success rate at 6 months postoperatively was not different between the groups (56.4% compared to 43.3%, p>0.05). Neither was the prevalence of postoperative hypotony, 5-fluorouracil injections, use of anti-glaucoma medications, bleb needling, and additional glaucoma surgeries different between the groups at 6 months. The authors concluded that all groups showed IOP reduction after XEN gel stent implantation, however there was no significant difference between the Ologen implant augmented and non-augmented groups in surgical outcomes.

Bhatkoti (2023) and Khairy (2023) also published small studies that assessed the use of Ologen implant in place of or in combination with trabeculotomy. Bhatoki (n=43) demonstrated a similar success rate between trabeculectomy and Ologen implant in treating primary open angle glaucoma. However, there was a lower complication rate and faster visual recovery in the trabeculectomy-only group compared to the Ologen group. Khairy (n=21) compared the use of Mitomycin C or Ologen implant as an adjunct to combined trabeculotomy-trabeculectomy in the treatment of primary congenital glaucoma. Complete success was achieved in 17 eyes (81.0%) in combined trabeculotomy-trabeculectomy group, 18 eyes (85.7%) in Mitomycin-C group, and 17 eyes (81.0%) in the Ologen group. Qualified success, defined as IOP < 21 with or without antiglaucoma medications, was achieved in 85.7% in both the combined trabeculotomy-trabeculectomy and the Ologen groups, and 90.5% in the Mitomycin C group. The Ologen group had the lowest success probability at 3 months (85.7%). The authors concluded that combined trabeculotomy-trabeculectomy is a safe and effective primary surgical treatment in individuals with primary congenital glaucoma without the need for implant augmentation, and that the use of Ologen implant should be preserved for use in recurrent cases. Additional larger studies are needed to assess the safety and clinical efficacy of Ologen in ophthalmic applications.

Pelvicol

Pelvicol is a porcine-derived acellular dermal collagen product cleared through the FDA’s 510K process. The use of Pelvicol was evaluated in 132 participants with pelvic organ prolapse. This RCT involved 64 participants who underwent anterior and posterior colporrhaphy and 68 who received colporrhaphy with Pelvicol. At 3 months follow-up, there were significantly more surgical failures and recurrences in the Pelvicol group, but by the 3-year follow-up period recurrence rates were similar. No significant differences were noted with regard to symptom resolution, sexual activity, or complications rates. The authors conclude that, “Pelvicol did not provide advantages over conventional colporrhaphy in recurrent pelvic organ prolapse concerning anatomical and subjective outcomes.”

Kahn (2015) published the results of an RCT involving 201 participants undergoing surgical treatment for stress urinary incontinence. Participants received treatment with either tension-free vaginal tape (TVT), autologous fascial sling (AFS), or Pelvicol. The authors reported that 162 (80.6%) participants were available for follow-up at a median follow-up of 10 years. They reported the 1 year “success rates”, defined as being completely dry or improved, as 93% in the TVT group, 90% in the AFS group and 61% in the Pelvicol group. There were no significant differences between groups at 10 years. Comparing the 1- and 10-year success rates, there were significant reductions in the TVT and AFS groups (p<0.05 for both), but not for the Pelvicol group (p=1.0). Similar results were reported with the rates of “dry” participants at 1 and 10 years, with rates for TVT reported as being 55% and 31.7%, 48% and 50.8% for AFS, and 22% and 15.7% for Pelvicol. These rates significantly favored AFS (p<0.001 vs. Pelvicol and p=0.001 vs. TVT). The Pelvicol arm of the study was discontinued by the data monitoring group after it was clear that the Pelvicol group had significantly poorer results vs. TVT and AFS. The results of this study indicate that the use of Pelvicol for the treatment of stress urinary incontinence may present a significant risk of harm compared to other available treatments, and further investigation may be warranted.

Peri-Strips Dry

Peri-Strips Dry is a product derived from decellularized bovine pericardium and cleared through the FDA’s 510K process. At this time there are only a limited number of peer-reviewed published article addressing the use of this product. Stamou and colleagues compared the use of Peri-Strips Dry (n=96) to standard care (n=91) in staple line reinforcement during sleeve gastrectomy procedures (2011). The authors reported that the use of Peri-Strips Dry significantly reduced the incidence of staple line bleeding (p=0.012) and intra-abdominal collections (p=0.026). Leak rate was not significantly reduced.

A similar study was conducted by Shah and others (2014) involving 100 participants undergoing sleeve gastrectomy procedures and assigned to surgery with either Peri-Strips Dry staple line reinforcement (n=51) or standard care (n=49). Participants were followed up for 30 days post procedure. No intra- or postoperative leaks were reported in either group. Staple line bleeds were reported to occur less in the Peri-Strips group vs. controls (45.1% vs. 79.6%, p=0.0005). Overall BMI did not impact staple line bleeds (p_interaction=0.072). However, participants with BMI < 43 were significantly more likely to have staple line bleeds compared to participants with BMI ≥ 43 (79.3% vs. 33%, p=0.0015). Participants in the Peri-Strips group had less severe staple line bleeding vs controls, with moderate to severe bleeding occurring in 2 Peri-Strips group participants vs. 6 controls (p=0.0002). Peri-Strips participants also had shorter procedure times (58.8 minutes vs. 72.8 minutes, p=0.0153) as well as fewer hemostatic clips or sutures (19.6% vs. 67.3%, p<0.0001).

The results of these studies are promising, however, further data from more rigorously designed and executed studies is warranted.

Permacol is an acellular dermal collagen product derived from porcine pericardium that has been cleared through the FDA’s 510K process. Currently, the peer-reviewed published data addressing the use of Permacol is limited. A retrospective, nonrandomized controlled study of 37 participants undergoing congenital diaphragmatic hernia repair was reported by Mitchell (2008). Participants received treatment with either Permacol (n=29) or synthetic Gore-Tex (n=8), with a median follow-up of 57 months for Gore-Tex and 20 months for Permacol. Overall recurrences were reported in 8 (28%) Gore-Tex participants with a median time to recurrence of 12 months. There were no recurrences reported in the Permacol group. These results are interesting, but due to the small sample size, retrospective nature and lack of randomization, it is not possible to generalize the results to other populations.

Kalaiselvan and colleagues (2020) performed a retrospective analysis of 13 participants who had abdominal wall defect repair with bridging Permacol over a 5-year period. Twelve of these (92%) participants developed abdominal wall defects (AWD) and enterocutaneous fistulation following complications of previous surgery. Six participants underwent fistula takedown and abdominal wall repair with Permacol, of which 5 (83%) recurred. Seven participants had already undergone similar procedures in their referring hospitals and had also recurred. Median time to fistulation after Permacol treatment was 17 days. In all cases, Permacol was used to bridge the defect and placed in direct contact with bowel. At reconstructive surgery for refistulation, it was inseparable from multiple segments of small intestine, necessitating extensive bowel resection. Histological examination confirmed that Permacol almost completely integrated with the seromuscular layer of the small intestine. The study raised concerns regarding intraperitoneal use due to the fact that Permacol may become inseparable from the serosa of the small intestine and was associated with recurrent intestinal fistula formation and treatment failure.

Rashid and colleagues (2020) examined rotator cuff repair augmented with either GraftJacket (n=4), Permacol (n=3) or SOC (n=3). The study addressed histological and proinflammatory changes in the native supraspinatus tendon in both Permacol groups. The authors reported increased friability of the matrix, and lack of parallel oriented collagen fibers. In the SOC group, which was a conventional repair without patch augmentation, the tissue resembled normal tendon. The Permacol-treated sections, however, demonstrated more disruption of the extracellular matrix when compared to sections treated with GraftJacket. They reported that one participant in the Permacol group experienced adverse tissue reaction characterized by extensive infiltration of pro-inflammatory cells. The authors concluded use of Permacol augmentation in rotator cuff repair lacks clinical efficacy and may potentially cause harm.

The studies discussed raise concerns about the broader use of Permacol in both abdominal wall reconstruction and rotator cuff repair. More robust studies are warranted to investigate these findings.

Roman (2021) reported the results of a retrospective case-control study of 209 participants undergoing complete excision of large rectovaginal endometriotic nodules treated with (n=167) or without Permacol (n=42) mesh. No significant differences were reported in the rate of postoperative rectovaginal fistula formation (OR, 1.6) and the authors concluded that the use of Permacol mesh may not impact the rate of rectovaginal fistula formation compared to no mesh.

Vahtsevanos (2021) reported the results of a retrospective case-control study of 73 participants who had undergone 76 parotidectomy procedures with (n=32) and without Permacol (n=44) to evaluate the impact on the incidence of Frey’s syndrome. At a mean follow-up of 26.3 months the incidence of Frey’s syndrome was significantly lower in the Permacol group (6.7% vs. 31.8%, respectively, p=0.031). The incidence of severe Frey’s syndrome was 3.12% in the Permacol group vs. 31.82% in the control group (p=0.002). The results of this study should be confirmed in a prospective trial.

Ball and colleagues (2022) conducted a parallel, dual-arm, double-blind randomized controlled trial involving adults (n=94) undergoing complex abdominal wall reconstruction with a biologic mesh (2017–2020). Participants were randomized in a 1:1 ratio to receive either Strattice or Permacol biologic meshes. The incidence of complications between groups was not statistically significant (46.0% v. 64.6%; p=0.06). A total of 14 (14.9%) participants experienced a hernia recurrence, with no differences between groups (n=6 in the Permacol group and n=8 in the Strattice group).

Further investigation into the clinical utility of Permacol is needed.

Promogran

Promogran is an acellular dermal collagen product of bovine origin cleared through the FDA’s 510K process. The use of Promogran has been evaluated in two RCTs. The first, by Veves and others, involved 276 participants with DFUs randomized to receive treatment with either Promogran (n=138) or moistened gauze (control group; n=138) (2002). At 12 weeks of treatment, there was no statistically significant difference between groups with regard to complete wound closure (p=0.12), in healing for either the subgroup of participants with wounds of less than 6 months duration (p=0.056), or the group with wounds of at least 6 months duration (p=0.83). No differences were seen in the safety measurements between groups. The other study by Vin involved 73 participants with VSUs randomly allocated to receive either Promogran (n=37) or a non-adherent dressing (Adaptic) (n=36). Only 29 participants completed the 12-week study period (39.7%). No intent-to-treat analysis was provided. Because of this, the data reported is not particularly useful.

Further study is required to fully assess the safety and efficacy of Promogran.

PuraPly

PuraPly AM antimicrobial wound matrix is an acellular dermal collagen product composed of a purified collagen matrix of bovine origin containing polyhexamethylenebiguanide (PHMB) cleared through the FDA’s 510K process.

Lintzeris (2018) published a case series involving 8 participants with chronic wounds with a variety of etiologies including trauma (n=1), DFUs (n=1), pressure ulcers (n=3), VSUs(n=1), surgical wounds (n=1), and calciphylaxis ulcers (n=1). PuraPly AM was applied once weekly after debridement. The authors reported a mean of 5.8 PuraPly applications were used. A total of 6 wounds had complete healing at an average time to closure of 10 weeks. The 3 wounds that did not completely heal demonstrated improved wound appearance with 100% granulation with an average area reduction 61.4%.

Bain (2020) published the results of the Real-World Effectiveness Study of PuraPly AM on Wounds (RESPOND) registry, a prospective cohort study involving 307 participants with wounds with a variety of etiologies including VSUs (n=67), DFUs (n=62), pressure ulcers (n=45), surgical wounds (n=54), and other wounds (n=79) treated with PuraPly AM. Participants were followed for 32 weeks. The authors reported the mean number of PuraPly AM applications as 5.2. Full wound closure was 52% at 20 weeks, 62% at 26 weeks, and 73% at 32 weeks. Complete wound closure for VSUs was 73%, for DFUs was 51%, for pressure ulcers 62%, for surgical wounds 96% and 67% for other wounds. No adverse events or serious adverse events attributable to PuraPly were reported.

Koullias and others (2022) completed a secondary analysis of the RESPOND registry examining the effects of PuraPly AM treatment in the subgroup of participants with VSUs (n=67) over 32 weeks. The use of PuraPly resulted in successful healing defined as > 60% reduction from baseline in wound area and depth, as well as the incidence of wounds demonstrating > 75% reduction from baseline in wound volume. This resulted in successful healing in 73% of participants as demonstrated by reduction in area, depth, and volume. A limitation of the study was the participants included were predominantly white (87%) females (58%).

Menack and colleagues (2022) also completed a secondary analysis of the RESPOND registry in a subgroup of participants with pressure injuries (PI) (n=45). The participants were primarily elderly, with large deep wounds of long duration. The use of PHMB in the management of PI resulted in 91% PAR and 62% rate of healing. While the evidence supports the PuraPly AM as a useful adjunct to SOC for treatment of chronic PIs larger randomized controlled trials are needed to further investigate the comparative effectiveness of this treatment to a wider population and to fully understand the clinical utility of PuraPly AM.

Regeneten

Regeneten is an acellular dermal collagen product of composed of bovine collagen. It has been cleared through the FDA’s 510K process.

Clinical use of the Regeneten graft has been described in several studies. The first, published by Bokor and others (2016) described a case series study of 13 participants with intermediate- to high-grade partial thickness rotator cuff tears who were followed for 2 years. At the end of the study 10 participants with evaluable tears had demonstrable improvement in tear appearance on MRI, with 7 completely healed. The remaining 3 participants had continued tears, but with continued improvement. No evidence of tear progression was reported. Clinical symptoms were shown to improve significantly in overall Constant-Murley shoulder scores (p≤0.01) and Constant-Murley pain score, (p≤0.001), as well as American Shoulder and Elbow Society (ASES) total score (p≤0.001), and ASES pain score (p≤0.001). No postoperative infections and no adverse events associated with the product were reported.

Schlegel reported the results of a prospective case series study involving 33 participants with intermediate-grade or high-grade partial-thickness tears of the supraspinatus tendon treated with Regeneten and followed for 1 year. Intermediate-grade tears were reported in 12 participants and or high-grade tears in 21. Of these, 11 were articular, 10 were bursal, 4 were intrasubstance, and 8 were hybrid). At 12 months, a total of 8 participants (24%) had no visible defect on MRI, 23 participants (70%) had a decrease in tear size by at least 1 grade. Only 1 participant (3%) had a tear that remained unchanged. No tears progressed to full-thickness tears in the participants who followed the postoperative rehabilitation protocol. No revision procedures were reported. Overall, tendon thickness increased significantly (p<0.0001) based upon MRI evidence of new tissue growth over the bursal surface of the supraspinatus tendon. The ASES pain score improved significantly at 1 year, as did the ASES shoulder function score and ASES shoulder index score (p<0.001 for all). No device-related significant adverse events were reported.

McIntyre (2019) published the results of a retrospective case series study involving data from participants with partial- and full-thickness cuff tears treated with Regeneten reported in the REBUILD registry. The registry included 203 participants and 173 (85%) had complete 1 year follow-up data. Overall, 90 participants had partial-thickness tears and 83 had full-thickness tears. Of the partial tear group, 16.7% were grade I tears, 37.8% grade II, and 45.5% grade III. Of the full-thickness tears, 4.8% were small, 50.6% medium, 30.1% large, and 14.5% massive. Other surgical procedures were conducted in conjunction with the graft placement, including acromioplasty (89.0%), acromioclavicular joint resection (39.9%), capsular release (12.1%), and biceps surgery (55.6%). At 12 months, the partial-thickness group has a statistically significant improvement with regard to outcomes on the single-assessment numeric evaluation (SANE), Veterans RAND 12-Item (VR-12) physical component, ASES, and Western Ontario Rotator Cuff (WORC) measures (p<0.05 for all). For the VAS pain and ASES scores, improvement was 84% and 83%, respectively, which met or exceeded each measure’s minimal clinically important difference (MCID). In the full-thickness group, a statistically significant improvement was reported at the 12 month point on the VAS, SANE, VR12 physical component, ASES, and WORC measures (p<0.05 for all). MCIDs were met or exceeded on the VAS and ASES tools in 72% and 77% of participants, respectively. Revision surgery for complications was required in 8 participants (4.6%). Indications included progression of a partial thickness tear to a full thickness tear, deep vein thrombosis and adhesive capsulitis, loose mobile graft remnant in the joint, recurrent effusions, and failure to heal. In the partial thickness group, 29 participants (32.2%) required corticosteroid injections in the postoperative period for pain control, and 9 participants (10.8%) in the full-thickness group required injections. The majority of post-operative steroid injections administered in the study were done in 2 centers accounting for 76% of injections. Nine sites did not administer any steroid injections.

Thon (2019) reported on the results of a prospective case series study of 23 participants with large (n=11) or massive (n=12) full-thickness rotator cuff tears treated with Regeneten. In addition to complete rotator cuff repair, participants underwent subacromial decompression (n=19), distal clavicle excision (n=17), biceps tenodesis/tenotomy (n=12), and suprascapular nerve release (n=5). Mean time to postoperative MRI was 13 months, and final ultrasound evaluation was 24 months. Complete healing on both measurements was reported to be 96%, with 2 treatment failures. No difference was found between the two tear groups with regard to final ASES scores (p=0.69). There were no postoperative infections or adverse events associated with the device.

The results of these studies are all promising, but the methodology used limit the generalizability of this data to larger populations. Additional studies are warranted to better understand the clinical utility of Regeneten for rotator cuff repair surgery.

Seamguard

Seamguard is a synthetic product composed of polyglycolic acid and trimethylene carbonate cleared through the FDA’s 510K process. It has been evaluated in only a few peer-reviewed published articles. The first, by Salgado and others, was a randomized controlled trial evaluating the use of Seamguard vs. extraluminal suturing or fibrin glue for open bariatric surgical procedures (2011). Twenty participants were assigned to each group; however, enrollment in the fibrin glue group was stopped due to serious complications, including leaks requiring surgical intervention. The authors report that no significant differences were found between the Seamguard group and the suturing group. This study was not designed or powered to be a non-inferiority study, so these findings are not particularly useful in understanding the safety and efficacy of Seamguard.

In another study by Albanopoulos and colleagues, Seamguard was compared to staple line suturing in laparoscopic sleeve gastrectomy procedures (2012). This study enrolled 90 participants, 48 who were assigned to the Seamguard group and 42 to the suturing group. As with the Salgado study, the authors reported no significant differences in measured outcomes. One exception to this was a 6.2% complication rate in the Seamguard group vs. no complications in the suturing group.

In 2013, Wallace published the results of a nonrandomized controlled study of 36 participants undergoing pancreatectomy with the addition of Seamguard to the stapled stump closure. This group was compared to 18 historical controls undergoing the same procedure without Seamguard. Postoperative leak rate was reported in 8% in the experimental group vs. 39% in the control group. This study is limited due to its small population, use of historical controls and other methodological issues. The available data addressing the use of Seamguard is limited to studies with significant methodological flaws. Further investigation with robust trials is warranted.

Guerrier and others (2018) published the results of a retrospective review of 256 participants undergoing laparoscopic sleeve gastrectomy. Participants received treatment with staple line reinforcement with oversewing (n=28), reinforcement with Seamguard (n=115), or no staple line reinforcement (n=111). Intraoperative staple line bleeding was significantly reduced in the reinforcement group (22.3 vs. 37.8%, p=0.003). Gastric leaks were reported in 9 participants (3.52%), with no difference between any reinforcement method (2.7 vs 2.1%, p=0.54). The authors did note that oversewing of the staple line was associated with higher incidence of stenosis, a serious complication with significant morbidity and mortality (p<0.01). The authors concluded that their study demonstrated that staple line reinforcement does not provide significant leak reduction but does reduce intraoperative staple line bleeding. However, this must be viewed in light of increased risk of stenosis development.

In a 5-year, single-center retrospective case-control study, Vitiello (2024) analyzed 626 individuals undergoing laparoscopic sleeve gastrectomy, comparing 450 procedures reinforced with GORE SeamGuard to 176 procedures without any staple line reinforcement. The no-reinforcement group experienced a 2.26% rate of leaks or bleeding, whereas the GORE SeamGuard group recorded 0% staple line complications (p<0.05). In addition, 13 external cases of staple line complications treated at the same center all involved laparoscopic sleeve gastrectomy performed without reinforcement. Although these findings suggest that GORE SeamGuard may help reduce complications in laparoscopic sleeve gastrectomy, the retrospective, single-center design limits the conclusiveness of the results. Further high-quality research with larger and more diverse populations is warranted.

SERASYNTH MESH BR

SERASYNTH MESH BR (Serag Wiessner GmbH & Co, Naila Germany) is a fully absorbable synthetic mesh composed of poly-p-dioxanone, intended for direct-to-implant breast reconstruction. In a retrospective single-center analysis by Gruber (2023) involving 32 mastectomies across 22 individuals without prior radiation, 15.6% experienced major complications (for example, hematoma or infections requiring revision), and 12.5% had minor complications such as seroma. Implants were replaced in each revision, and there were no significant differences between prophylactic and therapeutic mastectomies regarding complication rates (p=0.38) or esthetic outcomes (p=0.38). Although these findings suggest that SERASYNTH MESH BR has complication rates comparable to those reported for other synthetic meshes, further high-quality research with larger cohorts and longer follow-up is warranted.

STRAVIX

STRAVIX (Smith & Nephew, Andover, MA) is a cryopreserved allogeneic umbilical cord tissue product regulated by the FDA through the HCT/P pathway and designed to treat large, post-operative diabetic foot wounds with exposed tendon, muscle, or bone. In a single-blinded, 12-week randomized trial by Lavery (2024), 40 individuals with foot wounds classified as categories 2A through 2D or 3A through 3D in the University of Texas Wound Classification were assigned to receive either the cryopreserved version (Stravix) or a lyopreserved version at baseline and again after 4 weeks. After 12 weeks, wound closure was observed in 36.8% of the cryopreserved group and 19.0% of the lyopreserved group (p=0.21); infection rates were 10.5% and 4.8%, respectively (p=0.60). Mean reductions in wound area (75.9 ± 32.3% vs. 65.5 ± 38.4%, p=0.41) and wound volume (85.0 ± 30.8% vs. 79.9 ± 31.9%, p=0.61) were also not significantly different. Overall, infections were noted in approximately 7.5% of participants, which was lower than anticipated for this high-risk population. This study indicates no significant differences in clinical performance between a cryopreserved version or a lyopreserved version of Stravix. However, it is not clear how these products perform against other more widely used products. Additionally, due to the design limitations of this study, definitive conclusions cannot be made. Further high-quality research with larger populations is warranted.

Suprathel

Suprathel is a synthetic copolymer consisting mainly of DL-lactide (>70%), trimethylenecarbonate, and e-caprolactone and was cleared under the FDA’s 510k process. The available evidence addressing the use of Suprathel is limited. An RCT involving 22 participants with burn injuries treated with STSG was reported by Schwarze in 2007. Each donor site was randomly selected and was treated with Suprathel or Jelonet. There was no significant difference between the two materials tested regarding healing time and re-epithelization, but a significantly lower pain score was reported for the participants treated with Suprathel (p=0.0002). The same group reported the results of another RCT study involving 30 participants with burn injuries (Schwarze, 2008). Wounds from each participant were randomly selected and partly treated with Omniderm and partly treated with Suprathel. There was no significant difference between the two products regarding healing time and re-epithelization. There was a significantly lower pain score for participants treated with Suprathel (p=0.0072).

Rashaan (2017) reported the use of Suprathel in a population of 21 children with partial thickness burns. The authors reported a median reepithelialization time of 13 days (range 7-29), and 3 participants required treatment with split skin grafts. There were 7 (33%) participants with wound colonization before application of Suprathel, which increased to 12 (57%) during treatment. Only 1 participant developed a wound infection.

Nischwitz (2021) published the results of a prospective case series study involving 22 participants with chronic leg wounds treated with Suprathel and followed for 8 weeks. Out of the original participant pool, 19 participants completed the trial. No significant difference in average wound size was reported between baseline and 4 weeks (p=0.074). The wound size changed significantly between 4 and 8 weeks (p=0.031). Overall, the average wound size between baseline and 8 weeks decreased significantly (p=0.006). One wound was reported as healed at 4 weeks (5.3%) and two at 8 weeks (15.79%). When stratified by wound age < 12 months and > 12 months, the overall wound size had a significant reduction for both old and young wounds (p=0.002 and 0.03, respectively). Similar findings were reported for both diabetic (p=0.014) and non-diabetic wounds (p=0.028). No adverse event associated to the intervention had occurred in the study period.

Heitzmann and colleagues (2023) published a prospective intra-individual clinical study in 23 individuals with burn injuries aged 18 to 85 years that compared Suprathel and Jelonet in the treatment of deep dermal burns after enzymatic debridement. Individuals had sustained partial-thickness-to-deep-thickness flame, scald, or contact burns of their hands or feet, with more than 0.3% of TBSA. The outcomes measured were wound healing, participant comfort, and pain. Wounds were divided in 2 areas, one treated with Suprathel and the other with Jelonet. Suprathel was placed on the wounds and gradually cut back as the re-epithelialization progressed until the dressings were completely detached. The Jelonet dressings were changed every 2 days. Wound closure was documented with a mean of 18.44 days for wounds treated with Suprathel, and 18.81 days with Jelonet (p=0.58), with no significant difference in final wound healing time, only 1 individual had a second debridement followed by skin grafting. Less pain was reported during the dressing changes with Suprathel compared to Jelonet on day 2 (p<0.001) and day 4 (p<0.0). Additionally, the wound areas treated with Suprathel showed less exudation and bleeding. The authors concluded that both dressings achieve safe and rapid healing after the enzymatic debridement of deep dermal burns of the hands and feet. However, the results of this study require further investigation in the form of more robust and well-designed trials.

Karlsson (2023) reported a retrospective, single center study of 58 pediatric individuals with burns comparing Suprathel (n=30) to Mepilex^® Ag (n=28). The outcomes measured were healing time, burn wound infection, need for operations and number of dressing changes. The results showed that healing within 14 days occurred in 17 Suprathel group participants and 15 in Mepilex Ag group participants. A total of 10 participants from each group received antibiotics for suspected burn wound infection, and 2 from each group had skin grafting. The median number of dressing changes were 4 in each group. The authors concluded the results were similar with both Suprathel and Mepilex Ag dressings. However, they noted that these results to be interpreted with caution due to the retrospective study design, and the fact that burns were significantly larger in the Mepilex Ag group.

In a randomized controlled trial involving 40 individuals undergoing split-thickness skin graft procedures for non-melanoma skin cancer, donor sites were dressed in either Suprathel or Hypafix adhesive tape (Cussons, 2024). Of the original 40 participants, only 16/20 (80%) of participants in the Suprathel group and 14/20 (70%) in the Hypafix group completed the trial, resulting in a loss to follow-up of 70% . The results showed no statistically significant difference in mean time to healing (31.7 vs. 27.3 days, p=0.182), pain, itch, or final scar outcomes at 13 weeks, as measured by the Patient and Observer Scar Assessment Scale. Neither group had postoperative infections. Although these findings suggest that Suprathel may not provide clear advantages for older individuals with small-area donor sites, the trial’s methodological limitations prevent further conclusions. Further high-quality research with larger populations is warranted.

In a retrospective, single-center study by Delgado-Miguel (2024) involving 378 individuals under 18 years old, three skin substitutes (Suprathel [n=92], EZ-derm [n=179], and Biobrane [n=107]) were compared for short- and long-term outcomes in pediatric partial-thickness burns. Although the groups had similar demographics and burn characteristics, the Suprathel group exhibited a significantly shorter median hospital stay (p<0.01), lower escharectomy and grafting rates (p=0.018), and fewer long-term reoperations (p=0.031). No differences in long-term complications were observed between groups. While these findings suggest Suprathel may offer distinct advantages, the single-center, retrospective study design may limit generalizability. Further high-quality, multicenter research is warranted.

Overall, the evidence for the use of Suprathel consists of small, poorly designed trials. Additional investigation in the form of well-designed and conducted trials is needed to understand the clinical utility of this product.

Surgisis (also known as Biodesign)

Surgisis, also known as BioDesign, is a product composed of decellularized intestinal mucosa of porcine origin and is cleared under the FDA’s 510k process. Several forms of Surgisis/Biodesign are available, including Anal Fistula Plug (AFP), 4-Layer Tissue Graft, Dural Graft, Hernia Graft, and others. Cook Medical, the manufacturer of this product changed the name of Surgisis products to Biodesign in 2008. However, the medical literature continues to refer to these products by their former name.

At this time, there are a large number of case series studies published on the use of the Surgisis anal fistula plug (AFP) (Champagne, 2006; Cintron, 2013; Ellis, 2010; Ky, 2008; O’Connor, 2006; Schwandner, 2009; Thekkinkattil, 2009). The vast majority of these involve very small sample sizes and short follow-up times. The uncontrolled nature of these studies minimizes the scientific value of this data.

Several RCTs are currently available addressing the use of Surgisis for the treatment of anal fistulae. The first study, reported by Ortiz et al., involved 43 participants randomized to receive either endorectal advancement flap surgery or insertion of an anal fistula plug (2009). The drop-out rate was greater than 20% for each group. The authors reported that the relative risk for recurrence was 6.4 for those who received the plug intervention during the 1-year follow-up. Additionally, of the 16 who had previous fistula surgery, 9 had recurrence and 8 of these were from the plug group. Overall, the authors concluded that the anal fistula plug was associated with a low rate of fistula healing, especially in individuals with a history of fistula surgery. The second study included 60 participants with perianal fistulas who were randomly assigned to receive treatment with Surgisis (n=31) or a mucosal advancement flap (n=29) (van Koperen, 2011). Both participants and investigators were blinded to group assignment. At a follow-up of 11 months, the recurrence rates were 71% (n=22) in the Surgisis group vs. 52% (n=15) in the mucosal advancement flap group, which was not significantly different. Additionally, no significant differences were reported with regard to postoperative pain, pre- and postoperative incontinence scores, soiling, and quality of life. Senéjoux (2016) reported the results of an open-label, randomized controlled trial comparing seton removal alone (n=52) vs. Surgisis (n=54) in 106 participants with Crohn’s disease and at least one ano-perineal fistula tract drained for more than 1 month. The authors reported that fistula closure at week 12 was achieved in 31.5% of participants in the Surgisis group vs. 23.1 % in the control group (p=0.19). No interaction in treatment effect was found when data was analyzed to control for case complexity (p=0.45). Adverse events at week 12 were reported in 17 participants in the Surgisis group vs. 8 controls (p=0.07). The authors concluded that the use of Surgisis was not more effective than seton removal alone. In 2017, Bondi and others published the results of an RCT involving 94 participants with cryptogenic trans-sphincteric anal fistulas assigned to treatment with either Surgisis (n=48) or mucosal advancement flap (n=46). The authors reported that the recurrence rate at 12 months was 66% in the Surgisis group and 38% in the flap group (p=0.006). While anal pain was reduced after operation in both groups, anal incontinence did not change in the follow-up period for either. No differences between the groups were reported with regard to pain, incontinence, or quality of life. The authors concluded that there was a considerably higher recurrence rate after the anal fistula plug procedure than following advancement flap repair.

Several studies have reported on the results from nonrandomized controlled, retrospective trials. Ellis and colleagues described the results of a study that involved 95 control participants who had trans-sphincteric or rectovaginal fistulas repaired via advancement flap repair (2007). The experimental group included only 18 participants who received treatment with Surgisis. The results indicated a significant benefit to the Surgisis procedure. Another study included 80 participants who received treatment with either anal fistula plug or endorectal advancement flap (Christoforidis, 2009). The results of this trial demonstrated that treatment success was close to over twice as likely with the flap procedure compared to treatment with a fistula plug after a mean follow-up period of 56 months. Chung and colleagues (2009) reported on the results of a retrospective study that involved 245 participants who underwent anal fistula repair surgery with either Surgisis (n=27), fibrin glue (n=23), Seton drain (n=86), or an endorectal advancement flap procedure (n=96). The results indicate that the rate of success was similar between the Surgisis group and the endorectal advancement flap group. Hyman and others conducted a study that involved 245 participants who received one of seven procedures, including the Surgisis plug (n=43), endorectal advancement flap (n=4), Seton drain (n=34), fibrin glue (n=5), fistulotomy (n=156), and other unspecified procedures (n=3) (2009). In contrast to the findings of the Chung study, the authors reported that the Surgisis plug demonstrated the lowest success rate, with only 32% healed at 3 months vs. 87% for the fistulotomy group. In 2014, Blom reported on a case series study involving 126 participants with anal fistulae treated in four different hospitals. After a median of 13 months, 30 (24%) of the fistulae had closed with no discomfort or secretion reported. The outcomes in the four hospitals varied from 13% to 33% with similar numbers of participants in each hospital. A success rate of 12% was observed for participants with anterior fistula compared with 32% for those with posterior tracks [HR for successful healing, 2.98] and 41% for those with a lateral internal opening (HR, 3.76). The authors concluded that their study demonstrated low success rates after the first plug-insertion procedure and that anterior fistulae were much less likely to heal compared with fistulae in other locations.

Jayne (2019) reported on the results of an RCT involving 304 participants with anal fistula treated with either Surgisis or ‘surgeon’s choice” (e.g., fistulotomy, cutting seton, advancement flap or ligation of intersphincteric fistula tract [LIFT] procedure). The authors reported clinical evidence of fistula healing in 66 participants (54%) in the Surgisis group vs. 66 participants (55%) in the control group at 12 months. Furthermore, MRI data showed fistula healing in 54 participants (49%) in the Surgisis group vs. 63 participants in the control group. Overall, 12-month clinical healing rates were 55% in the Surgisis group vs. 64%, 75%, 53%, and 42% in the cutting seton, fistulotomy, advancement flap and LIFT procedure groups, respectively. The authors commented that overall, there was no significant difference between the use of Surgisis and other procedures.

A meta-analysis was reported by Lin (2019) that included 11 studies comparing the use of Surgisis to rectal advancement flap (RAF) for anal fistula repair in 810 participants. They reported that the pooled analysis indicated that there was no significant difference between the use of Surgisis and RAF in terms of healing rate, recurrence rate and incidence of fistula complications. However, the pooled results of the 4 RCTS and 1 series study with long-term follow-up revealed that the RAF group had a significantly higher healing rate (OR, 0.32; p=0.01) and lower recurrence rate (OR, 4.45; p=0.009) than the AFP group. These results appear to support the use of RAF over Surgisis for anal fistula repair.

Jayne (2021) published the results of an open-label RCT involving 304 participants undergoing anal fistula repair. Participants were assigned to treatment with either Surgisis anal fistula plug (n=152) or surgeon’s preference (advancement flap, cutting seton, fistulotomy, Ligation of the Intersphincteric Fistula Tract procedure, n=152). At 12 months, the authors reported no significant differences between groups with regard to rate of clinical healing (54% in the Surgisis group vs. 55% in the surgeon’s preference group, p=0.83). Similar findings were reported with regard to MRI-confirmed healing (49 vs. 57%, respectively, no p-value provided). Additionally, no significant differences between groups were reported at 12 months on the St. Mark’s incontinence score (p=0.48), complication rate (23% vs. 20%, p=0.6), or rate of reintervention (23%. Vs. 22%, p=0.96). These results indicate that the use of Surgisis is equivalent to other surgical approaches to anal fistula repair.

Due to the conflicting evidence discussed above, further data is needed in the form of large, well-done, double-blind RCTs in order to properly understand the efficacy of Surgisis for the treatment of anal fistulas.

Unlike the anal fistula plug product discussed above, Surgisis Gold is provided in larger sheets. Sarr and others (2014) conducted an RCT involving 380 participants with body mass index (BMI) ≥ 35 kg/m² scheduled to undergo open Roux-en-Y gastric bypass surgery. Participants were randomized to receive standard suture closure alone or Surgisis Gold as a reinforcing adjunct. The authors reported that complications were more common in the Surgisis Gold group with significantly more wound events and seroma formation compared with the suture closure alone group. At final follow-up of 2 years post-procedure, 32 of 185 (17%) participants in the Surgisis Gold group and 38 of 195 (20%) in the control group developed an incisional hernia (p=0.6). Based on these findings, it would seem that the use of Surgisis Gold is not warranted, and further investigation is needed regarding the safety and efficacy of this product.

Korwar (2019) retrospectively reported the treatment of PEH in 154 consecutive participants who underwent standardized laparoscopic suture repair of the hiatus with Surgisis reinforcement. Follow-up barium swallow was performed in 122 participants (79.22%). Symptomatic recurrence was noted in 25 participants (28.73%), and recurrence on barium swallow was noted in 25 participants (20.4%). Both symptomatic and barium swallow recurrence were reported in 10 participants (12.98%). The reoperation rate was 3.25%. The authors concluded that use of Surgisis Biodesign for PEH repair is safe. They further commented that there was a high recurrence rate in long-term follow-up, but that the majority of recurrences are small, asymptomatic, and the reoperation rate is very low.

Surgisis Biodesign was also described in the repair of pelvic floor reconstruction following levator abdominoperitoneal excision of the rectum (Thomas, 2019). This retrospective case series study involved 100 participants, for whom 1-, 2-, and 5-year mortality rates were 3, 8 and 12%, respectively. The authors reported that 33 perineal wounds had not healed by 1 month, but no mesh was infected, and no mesh needed to be removed. Only 1 participant developed a symptomatic perineal hernia requiring repair. On review of imaging, an additional 7 asymptomatic perineal hernias were detected. At 4 years the cumulative radiologically detected perineal hernia rate was 8%.

Ravo (2019) described the results of a trial of 104 participants with inguinal hernia repair with a continuous suture of transversalis to transversalis fascia repair reinforced with Surgisis. Long term follow-up was scheduled at 1 week, 1 month, 1 year, 3 years, 7 years, and 10 years, and was achieved in 100%, 100%, 99%, 93%, 89% and 85% of the participants, respectively. The authors reported a recurrence rate of 1.9% (2 participants, one at 1 week in a participant with bilateral IH and one at 7 years). The mean recovery time was 1.2 days (range 1-5 days). Mortality was 0(0%).

In 2021 Alexandridis and others reported the results of a retrospective case series involving 155 participants with pelvic organ prolapse treated with Surgisis. A total of 138 (89.0%) participants completed the 3-month clinical visit, with 12 of the 17 participants not seen being contacted by telephone and included in the analysis of complications. At 3 months, 22 participants (15.9%) had Pelvic Organ Prolapse Qualification system (POP0Q) stage ≥ 2. The overall recurrence rate for Surgisis-treated defects was 11.6%. Reoperations were reported in 13 (8.4%) participants due to prolapse. Additionally, 7 participants experienced prolapse-related symptoms postoperatively, but had no record of reoperation. This data represents a subjective failure rate of 12.9%. Perioperative and postoperative complications occurred in 56% of participants. The most common complications were urinary (n=28) and pain (n=18). Major complications were reported in 8 participants (5.3%). Persistent complications at 3 months were reported in 28% of participants, including vaginal deformations, dyspareunia, stress urinary incontinence, urge urinary incontinence, and pain. Statistical analysis for recurrence identified a significant effect only for previous prolapse surgery at the same compartment as the Surgisis application (p=0.028). Other significant predictors for complications included lower age (p=0.034), smoking (p=0.022) and longer duration of surgery (p=0.003). The authors concluded, “The relatively high recurrence rates do not suggest a clear benefit from SIS graft use.”

Additional evidence is needed from larger, well-designed trials to fully understand the safety and efficacy of Surgisis/Biodesign for conditions other than anal fistulas.

Talymed

Talymed is a synthetic product composed of poly-N-acetyl glucosamine (pGIcNAc) isolated from microalgae and is cleared under the FDA’s 510k process. At this time, only a single RCT is available addressing the use of Talymed (Kelechi, 2011). In this reviewer-blinded trial, 82 participants with VSUs were randomized to receive either standard care (n=20) or to 1 of 3 groups that received standard treatment combined with different treatment frequencies with Talymed: (1) applied only once, (2) applied once every other week, or (3) applied once every third week. Seven participants were lost to follow-up, 5 from the 1 application group and 2 from the every 3-week group. Additionally, another 4 participants were withdrawn from the study, 3 from the 1 application group and 1 from the every 3 weeks group. This left 62 participants in the experimental group and 20 in the control group. At 20 weeks, the authors report that 45.0% (n=9 of 20) of participants receiving standard care alone had complete healing, while 45.0% (n=9 of 20), 86.4% (n=19 of 22), and 65.0% (n=13 of 20) of participants receiving Talymed only once, every other week, and every 3 weeks, respectively, had complete healing. This single study is insufficient to allow proper evaluation of the safety and efficacy of Talymed.

TAPESTRY RC Bionintegrative Implant

TAPESTRY^® RC (Zimmer Biomet, Warasaw, IN) is a composite implant composed of PDLLA and non-crosslinked bovine collagen. It is designed for managing and protecting tendon injuries where there is no significant loss of tendon tissue. The implant was cleared by the FDA through the 510(k) process.

TIGR Matrix Surgical Mesh

TIGR Matrix Surgical Mesh is a synthetic polymer made of lactide, glycolide, and trimethylene carbonate and is cleared under the FDA’s 510k process. It is indicated for use in the reinforcement of soft tissue plastic and reconstructive surgery, or for use in procedures involving soft tissue repair, such as for the repair of hernias or other fascial defects.

Hansson and colleagues (2020) reported a prospective, single-blind, clinical trial of 24 individuals (n=48 breasts) with bilateral mastectomy and immediate breast reconstruction. Participants were randomized to receive biological Veritas Collagen Matrix on one side and synthetic TIGR Matrix Surgical Mesh on the other side. During the 12‐month follow-up the 2 meshes yielded significantly different esthetic results and asymmetry. Due to this finding, recruitment to the study was terminated. No participants were lost to follow‐up at 12 months and 24 breasts in each group had an analysis of complications at 1 year postoperatively. All mastectomies were nipple‐sparing. The most common complication was seroma formation (38% in the Veritas group vs. 3.8% in the TIGR group, p=0.011). All TIGR meshes were completely integrated during the exchange to a permanent implant, the Veritas meshes were poorly integrated in the participants with seroma. The frequency of total implant loss (stage I + II) in the Veritas mesh group was 8.5% vs. 2% in the TIRG group (p=0 .083). There were 2 implant losses and re‐operations which were suspected to have been caused by penetration due to thin mastectomy flaps in the same participant. The authors concluded that there is a higher risk for complications, particularly seroma and implant loss, with Veritas vs. TIGR. However, more robust studies with larger sample sizes are needed to confirm these finding with a high degree of certainty.

Paganini and colleagues (2022) reported the results of a blinded, randomized, prospective trial that compared participant-reported outcomes after immediate breast reconstruction with TIGR mesh and Veritas mesh using the compared materials in the same participant. Twenty-four participants were recruited and all had a prophylactic bilateral mastectomy and a dual-plane reconstruction. There were no capsular contractures in either group at 5 years. No significant differences between groups were reported with regard to reported outcomes. The authors stated that the two products resulted in different types of reconstructed breasts, but concluded that the study was limited by its small sample size, varying surgical techniques, and variability in the meshes used, therefore more studies are needed to generalize the findings.

Additional larger studies with improved methodologies are needed to demonstrate the clinical efficacy and safety TIGR surgical mesh for use in breast reconstruction.

TiLoop Bra/TiLoop Bra Pocket^®

TiLoop Bra (pfm medical; Cologne, Germany) is a synthetic titanised polypropylene ready-to-use mesh pocket indicated for breast reconstruction/augmentation. The product comes in two forms: TiLOOP Bra Pocket (pre-pectoral), and TiLOOP^® Bra (sub-pectoral). It is purported to be superior to polypropylene because the hydrophilic and titanised surface carries a reduced risk of inflammation and thus a decreased tendency towards the formation of scars and shrinkage, resulting in permanent, stable tissue ingrowth and vascularized, flexible, optimal capsule quality.

There are multiple studies published addressing the use of TiLoop. However, this product is not currently approved or cleared by the FDA and is not available in the U.S.

Tutomesh

Tutomesh is a product composed of decellularized bovine pericardium and is cleared under the FDA’s 510k process. The literature addressing this product is sparse at this time. A retrospective review with 41 participants who underwent 52 breast reconstructions using ADMs was reported by Paprottka (2017). Participants received treatment with either EpiFlex (not available in the US, n=15), Strattice (n=21), or Tutomesh (n=16). Follow-up was 36 months (range 12-54). Overall complication rate was 17%, and 7% for the EpiFlex group, 14% for the Strattice group, and 31% for the Tutomesh group. Capsular contracture occurred in 6%, more frequently in this study compared to the current literature. The authors recommended the use of human derived grafting materials (EpiFlex) over those from porcine of bovine sources.

Eichler (2017) published a retrospective, nonrandomized comparative trial involving 54 participants undergoing breast reconstruction procedures using either SurgiMend (n=18) or Tutomesh (n=27) (Eichler, 2017). No difference in complications rates was noted, consistent with other previous reports.

Additional investigation into the safety and efficacy of this product is needed.

Vascu-Guard

Vascu-Guard is a decellularized product derived from bovine pericardium cleared under the FDA’s 510k process. Please see the section for Gore^® Acuseal Cardiovascular Patch above.

Veritas

Veritas is a decellularized product derived from bovine pericardium cleared under the FDA’s 510k process. The available evidence addressing Veritas is currently limited to a single RCT of 94 participants assigned to treatment with either anterior colporrhaphy alone vs. colporrhaphy reinforced with Veritas bovine pericardium graft (Guerette, 2009). This study had significant loss to follow-up, with only 72 of 94 (76.6%) participants at the 1-year time point and 59 of 92 (64.1%) at the completion of the study at 2 years. The authors report no significant differences between groups.

Quah (2019) published the results of a retrospective, non-randomized controlled trial involving 215 participants undergoing mastectomy and implant-based reconstruction procedures with either Veritas (n=36) or TiLOOP^® Bra (n=179), a product not currently approved for use in the U.S. In the Veritas group, 22 participants underwent unilateral procedures and 7 underwent bilateral procedures. In the TiLOOP group 61 participants underwent unilateral procedures and 59 participants underwent bilateral procedures. The authors reported that the Veritas group had a higher rate of postoperative complications when compared with the TiLOOP group (54% vs. 14%, respectively; p<0.01%). This included higher rates seroma (51.4% vs. 1.7%, p<0.01), nonintegration of mesh (51.4% vs. 1.6%, p<0.01), implant rotation (16.2% vs. 1.6%, p<0.01), infection (18.9% vs. 2.1%, p<0.01), and wound breakdown (10.8% vs. 0.5%, p<0.01). Additionally, when compared to the TiLOOP group, the Veritas group also had a higher rate of major interventions (35.1% vs. 7.8%, p<0.01), minor interventions (18.9% vs. 2.2%, p<0.01), implant loss (8.1 vs. 1.7%, p=0.05), and unplanned return to theater (27% vs. 6.1%, p<0.01). The results of this trial indicate that Veritas, at least when compared to TiLOOP Bra, results in significantly poorer outcomes.

Additional investigation into the clinical utility of Veritas is warranted.

VersaWrap

VersaWrap (Alafair Biosciences, Inc., Austin, TX) is a plant-based surgical mesh composed of hyaluronic acid and alginate. It is designed to manage tendon injuries, protect tissues such as skeletal muscle and ligaments, and serve as a nerve wrap for certain peripheral nerve injuries. The product can be applied as a sheet or a gel, creating a gliding interface to reduce friction and minimize postoperative complications like tethering. VersaWrap received FDA clearance through the 510K process in June 2016.

Hones and colleagues (2023) conducted a single-center retrospective review assessing VersaWrap’s effectiveness as a nerve protector during surgical decompression and neurolysis for recurrent compressive neuropathies in the upper extremity. The study involved 20 individuals with recurrent carpal tunnel syndrome (n=5), cubital tunnel syndrome (n=14), and radial tunnel syndrome (n=1). With an average follow-up of 139 days, all participants had previously undergone surgery at the same site, and symptoms had persisted for an average of 2 years before revision surgery with VersaWrap. Postoperative assessments included two-point discrimination, range of motion, muscle power, and standardized scores like DASH and VAS. No intraoperative complications or further revision surgeries were reported. Results showed mean DASH scores of 54.0 (cubital), 66.2 (carpal), and 68.3 (radial), and VAS scores of 2.7, 4.2, and 3.0, respectively. The authors concluded that VersaWrap was a safe and effective nerve protector, though the study was limited by its small size and non-comparative design. Postoperative outcomes measures included static and moving two-point discrimination, range of motion (ROM), muscle power and standardized scores including the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and Visual Analog Scale (VAS). No intraoperative complications or further revision surgeries were reported. Results showed mean DASH scores of 54.0 (cubital), 66.2 (carpal), and 68.3 (radial), and VAS scores of 2.7, 4.2, and 3.0, respectively. The authors concluded that VersaWrap is a safe and effective nerve protector. However, the study's non-comparative design and small cohort size limit its generalizability. Further comparative studies are necessary to validate these findings.

VIA Disc NP

VIA Disc is a processed human nucleus pulposus tissue allograft treated as human tissue for transplantation under the FDA’s HCT/P process.

The currently available published literature addresing this product is limited. Beall (2021) reported the results of the VAST RCT involving 218 participants with single- or two-level degenerative disc disease assigned to treatment with either saline injection (n=39), conservative care (n=39), or VIA Disc (n=140). A total of 36 participants (17%) were lost to follow-up or had withdrawn from the study by the 12 month follow-up point (n=7 [18%] saline group, n=12 [30%] conservative group, and n=17 [12%] VIA Disc group), leaving 182 participants completing the trial. There were 58 participants treated at least one intravertebral level outside of the predefined levels of degeneration for inclusion. Younger participants were reported to have had a more favorable outcome vs. older participants in regard to improvement in Oswestry Disability Index (ODI) for participants less than the median age (32 years old, p=0.004). Clinically meaningful improvements were observed in the VIA Disc group, with a mean reduction in ODI of 27 at 12 months (no p-value provided). ODI-based function was noted to have worsened in the conservative care group during the first 3 months and all participants in this group crossed over to the VIA Disc group in an unblinded fashion. Results for both VIA Disc groups were similar at 12 months. Mean pain reduction as represented by change in Visual Analog Scale of Pain Intensity (VASPI) at 12 months was reported to be 30.5, 34.0, and 46.7 for the saline, VIA Disc, and conservative/crossover groups, respectively. Mean functional improvement per ODI was 23.9, 27.4, and 36.5 respectively (no p-values provided). No differences between participants treated at a single vs. two levels was noted. A modified intention-to-treat analysis indicated significant differences between the VIA Disc vs. saline groups, with a ≥ 15-point reduction in ODI measures (p=0.030). No significant differences were found between groups with regard to number of participants achieving a 50% reduction in pain at 12 months (p=0.467). In an ad hoc analysis of responders in all groups, participants in the VIA Disc and conservative/crossover groups achieved a statistically significant reduction in pain vs. saline group participants (p=0.022). There were 66 (29.8%) total adverse events in the VIA Disc group vs. 5 (13.2%) in the saline group (no p-value provided). Twenty-three potentially VIA Disc-related events were reported, vs. none in the saline or conservative treatment only groups. The conservative/crossover group experienced 7 VIA Disc-related events (8.6% of participants in the crossover group). Most events in the VIA Disc group were musculoskeletal and connective tissue related, with 41 total events (22.0%) and 14 VIA DISC-related events (9.2%). The most common event was pain. In the saline group no adverse events were reported, while the conservative/crossover group reported back pain as a related event in 2.9% of participants.

A total of 11 serious adverse events were reported in the VIA Disc group (3.5%), with 6 considered possibly related to the treatment and/or procedure. Reported events included pain, back pain, bacteremia, and osteomyelitis. No serious events were reported in the saline group or conservative treatment only groups. One serious adverse event (2.6%) was reported in the conservative/crossover group (p=0.832). The 1 SAE in the crossover group was considered not related to treatment or procedure. The results of this trial indicate some potential benefit to the use of VIA Disc, but several methodological flaws limit the generalizability of this trial, including significant loss to follow-up, cross over of a large percentage of the control group to active treatment, loss of blinding, and others.

Hunter and colleagues (2021) published the results of a post hoc analysis of the VAST trial data exploring it stratified by age. They reported that participants younger than 42 years of age experienced significantly more improvement from treatment with VIS Disc than those older than 42 when compared to those in the saline treatment group. Furthermore, they noted that in participants older than 42 years of age, no differences between groups were seen with regard to functional benefit. As noted above, the VAST trial has several significant methodological flaws and additional investigation is warranted to assess the clinical utility of VIA Disc.

VICRYL Mesh

VICRYL (polyglactin 910) Mesh (Ethicon, Inc. /Summerville, NJ) is a synthetic absorbable sterile copolymer made from glycolide and L-lactide. VICRYL may be used wherever temporary wound or organ support is required (kidney, liver, spleen), and may be cut to the shape or size desired for each specific application. VICRYL mesh was approved via the FDA’s 510K process in 2019.

Xelma

Xelma consists of amelogenin proteins purified from porcine teeth, propylene glycol alginate (PGA), and water. It has not yet received marketing approval or clearance by the FDA. Amelogenin is a cell adhesion protein, and when suspended in a gelatinous matrix has been proposed to promote cellular growth. The use of Xelma was reported in a single-blind randomized trial involving 123 participants with VSUs (Vowden, 2006). Participants were assigned to receive treatment with either Xelma plus compression therapy (n=62) vs. a mixture of PGA and water plus compression therapy (n=61) and were followed for 12 weeks. The authors of this study state that Xelma outperformed the control group in multiple factors, including percentage of wound size reduction. However, no statistical analysis is presented to support these claims. No data on complication rates was provided. Further investigation into the clinical safety and efficacy is warranted.

XenMatrix

XenMatrix is an acellular dermal collagen product of bovine origin cleared through the FDA’s 510K process in May 2014. It is specifically indicated for the repair of colon, rectal, urethral, and vaginal prolapse; reconstruction of the pelvic floor; and procedures such as sacrocolposuspension and urethral sling.

Ilahi (2023) reported the results of a prospective case series study involving 75 participants undergoing ventral/incisional midline hernia repair using XenMatrix. The authors reported on surgical site occurrence in the first 45 days post-implantation and length of stay, return to work, hernia recurrence, reoperation, quality of life, and surgical site occurrence at 1, 3, 6, 12, 18, and 24 months. A total of 16 participants (21%) did not complete the study, resulting in complete data for 59 participants (79%). Overall, hernia recurrence was reported to be 5.8%. Device-related adverse events occurred in 4.0% of cases, and reoperation in 10.7%. Only one case of mesh infection was reported (1.3%) and no graft removal were needed. Surgical site occurrence requiring intervention within 45 days post-implantation was reported in 14.7% of participants, and 20.0% >45 days post-implantation. Surgical complications were evaluated according to the Clavien–Dindo system, with very few grade IVa, IVb, and V hernia-related complications (3%). Complications judged to be grade IIIa or IIIb occurred 37% of participants. The most common hernia-related complications seroma (n=14), bowel obstruction (n=9), pain (n=8), Ileus (n =4), incisional cellulitis (n=4), and surgical site infections (n=4). This study is impaired by several factors, including low power, lack of blinding and comparison groups, and others. Further, the significant loss of complete data makes these results difficult to interpret.

Other studies involving the use of XenMatrix are discussed elsewhere in this document for abdominal wall defect repair (Huntington, 2016; Rosen 2013). Those results are not generalizable to a wider population.

Overall, the evidence addressing the use of XenMatrix in the clinical setting is limited and not generalizable to a wider population. Additional evidence addressing the clinical utility of this product from large, well-designed, and conducted trials is needed to fully assess the clinical utility of this product.

Recommendations from Authoritative Organizations

In 2020 the American Academy of Ophthalmology published a report titled Bioengineered Acellular Dermal Matrix Spacer Grafts for Lower Eyelid Retraction Repair. In this document they reviewed the available literature and provided recommendations for the use of such products. They observed that there is no level I evidence available on this issue, and that the existing level II and level III studies have variable primary end points, study design limitations, and only short-term follow-up. Their conclusions included “…the materials used may fill an important gap in care for patients for whom no acceptable alternatives exist, but long-term safety and efficacy remain unknown.”

Regulatory Processes for Grafting Materials

Soft tissue grafting materials find their way to U.S. market through several regulatory pathways. Oversight for all these pathways is provided by the U.S Food and Drug Administration (FDA).

The first and most rigorous regulatory path is the Premarket Approval (PMA) Process, which is detailed in the Code of Federal Regulations Title 21 Part 860. Devices required to undergo this process are those deemed to present the most risk of harm to the public. The PMA process involves several steps of pre-clinical and clinical trials (Phase 0 through III). Each step is reviewed by the FDA to evaluate safety and efficacy data. If the FDA finds the data presented acceptable, a larger and more robust study is authorized until Phase III trials have been completed. Devices which pass Phase III are deemed “Approved” by the FDA and may be marketed in the U.S. This path was used in only a small minority of products addressed in this document. More information regarding the PMA process can be found at: https://www.fda.gov/medical-devices/premarket-submissions/premarket-approval-pma.

The “510K” process, also referred to as the Premarket Notification (PMN) process, is named after Section 510(k) of the Food, Drug and Cosmetic Act. This section of the Act requires manufacturers of devices that qualify to notify the FDA of their intent to market a medical device at least 90 days in advance. This law applies to any device that: (1) is not required to undergo review under another pathway, (2) was not already in commercial distribution prior to May 28, 1976, and (3) is to be introduced into commercial distribution for the first time or reintroduced in a significantly changed or modified form that alters its safety or effectiveness. The regulations stipulate that devices applying for 510K clearance must demonstrate that they are substantially equivalent to a device with prior PMA approval or marketed prior to May 28, 1976. No significant new data addressing safety or efficacy is required g this process. Devices with this type of review may or may not have undergone rigorous clinical testing to establish the presence or absence of these attributes. Devices passing through this pathway are referred to as “cleared.” More information regarding the 510K process can be found at: https://www.fda.gov/medical-devices/premarket-submissions/premarket-notification-510k.

A Humanitarian Device Exemption (HDE) is a regulatory path similar to a PMA but is exempt from the effectiveness requirements of sections 514 and 515 of the Code of Federal Regulations Title 21 Part 860, which details the PMA process. A device approved under an HDE is referred to as Humanitarian Use Device (HUD). An HUD is defined as a “medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year.” The HDE process is intended to facilitate the development of devices that could benefit individuals with rare conditions for whom medical devices are unlikely to be developed through the PMA process. Devices covered under this regulation are exempt from many of the PMA requirements, but have certain restrictions placed on their use outside the investigational setting. More information regarding the HDE process can be found at: https://www.fda.gov/medical-devices/device-approvals-denials-and-clearances/hde-approvals.

There is a specific pathway available for biological tissue derived from human sources deemed as “minimally manipulated.” The FDA Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/P) is addressed in the Code of Federal Regulations Title 21, volume 8, Part 1271 “Human Cells, Tissues, And Cellular and Tissue-Based Products.” These regulations detail the use of human autologous and allographic tissues for transplantation. They specify that “minimally manipulated” tissues undergo proper safeguards to prevent infection or other safety hazards. It should be made clear that products that reach the market through the HCT/P process do NOT require any testing to prove clinical safety or efficacy. Thus, their performance when used in the treatment of human participants may or may not have been tested in clinical trials. Human-derived tissues that are deemed to have been more than minimally manipulated are required to undergo one of the other regulatory pathways described above. HCT/Ps are regulated under 21 CFR 1271.3(d)(1) and Section 361 of the PHS Act, which can be found at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=1271.

In the vast majority of cases, soft tissue grafting products are considered devices by the FDA. However, in some rare cases, based upon the composition, preparation, and method of delivery, some products may be considered drugs and reviewed under the FDA’s drug regulatory process. Only one product addressed in this document has been so treated and is designated an Orphan Drug. This designation for drugs is similar to the HDE designation for devices. The Code of Federal Regulations Title 21, Part 316 details the “Orphan Drug” process and defines an Orphan Drug as a drug intended for use in a rare disease or condition as outlined in section 526 of the Act. As with HDEs, the Orphan Drug designation is intended to facilitate the development of drugs that could benefit individuals with rare conditions for whom drugs are unlikely to be developed through other regulatory processes. More information regarding the Orphan Drug designation can be found at: http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/default.htm.

Skin Wound Care

The skin is the largest organ of the body. It is composed of two layers, the epidermis, and the dermis, and provides functions critical to survival. The skin acts as a protective barrier to fluid losses and dehydration and it protects against infection and injury by providing a barrier to repel bacteria and other organisms. The skin provides sensory contact with our environment that tells us whether we are feeling light touch, pressure, pain, heat, or cold. Damage to the skin that is extensive or prolonged may interfere with these functions or with those of other body systems and may become life-threatening in some circumstances.

The treatment of burns and other wounds that have failed to heal despite conservative measures, referred to as chronic wounds, creates a significant burden on the population in terms of pain, disability, and decreased quality of life. Chronic wounds may be due to the effects of diabetes, venous insufficiency to the extremities, pressure due to prolonged periods in the same body position, and other types of skin injuries. They can be difficult to treat and may require treatment with various coverings, such as skin grafts or other materials to prevent infection, maintain an environment conducive to healing, or provide a medium for re-growth of new skin. Such coverings come in a wide array of types including synthetic materials, tissues from the individuals themselves (autologous), human donors (allogeneic), or from animals such as cows and pigs (xenographic), or any combination of these materials (composites).

The American Diabetes Association (ADA) published Standards of Medical Care in Diabetes in 2025 included the following recommendation regarding DFUs:

12.32  For chronic diabetic foot ulcers that have failed to heal with optimal standard care alone, adjunctive treatment with randomized controlled trial–proven advanced agents should be considered. Considerations might include negative-pressure wound therapy, placental membranes, bioengineered skin substitutes, several acellular matrices, autologous fibrin and leukocyte platelet patches, and topical oxygen therapy.

Level of evidence A: Defined as Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered, including:

• Evidence from a well-conducted multicenter trial
• Evidence from a meta-analysis that incorporated quality ratings in the analysis

Surgical Reinforcement Procedures

In a wide variety of surgical procedures, there may be a need for additional reinforcement of soft tissues to strengthen the structures being repaired, such as in abdominal wall repair or orthopedic reconstruction procedures. Traditionally this task is undertaken with the use of allogeneic cadaver-derived grafts or synthetic materials such as polypropylene and Gore-Tex^®. However, in some cases such materials may not be appropriate, and other materials have been sought.

In other circumstances, the use of grafting materials has been suggested as substitute for surgery.

Product types:

Allogeneic Products

There are currently several different types of allogeneic (human-derived) wound care products available. One type involves the use of donated human cadaver skin which is then treated with various methods to remove the cellular material and deactivate or kill pathogens (e.g., AlloDerm, GraftJacket, and Neoform Dermis). This process leaves only the collagen protein scaffold, which has been proposed as an acceptable medium for which new skin cells from the individual can populate and grow into when placed over a wound site.

Another type of allogeneic product includes composite products that may contain human skin cells, keratinocytes and/or fibroblasts (depending upon the product), which are imbedded into a decellularized collagen protein scaffold derived from a xenographic source (e.g., Apligraf, OrCel). Some of these products may also consist of layers of synthetic materials like silicone, nylon, or polyglactin (e.g., Dermagraft).

Autologous Products:

A product derived from the individual’s own body or body products

Bioengineered autologous skin-derived products

Bioengineered autologous skin-derived products (for example, MyOwn Skin, SkinTE) involve the harvesting of skin from an individual, which is then processed in a lab where it is altered in a manner that has been proposed to enhance it as a healing vector for wounds.

In a 2022 Cochrane review, Thompson and colleagues compared licensed bioengineered nerve conduits or nerve wraps used in surgical repair of traumatic peripheral nerve injuries of the upper extremity, to the current gold standard surgical technique (microsurgical repair with use of nerve autografts). The authors concluded that the evidence does not support the use of nerve repair devices over standard repair. There was significant heterogeneity in study methodologies, participants, injury pattern, repair timing, and outcome measures across the studies of the bioengineered devices, this made comparisons unreliable. The studies were also small and at risk of bias which made the overall certainty of evidence low or very low. The data provided some evidence that more people may experience adverse events with the use of bioengineered devices than with standard repair and may also be at increased need for revision surgery. There was no data for a primary outcome measure (muscle strength) at 24 months and sensory recovery was uncertain. Additional trials with improved methodologies and a minimum of 12 months' follow-up are needed to analyze the safety and clinical efficacy of bioengineered nerve repair devices.

Composite Products

Composite products are created from a variety of materials of combined origins. Such products usually combine an allogeneic or xenographic collagen-based product with a synthetic one (for example, Avaulta Plus, Integra Matrix, and Integra Bilayer Matrix). Additionally, the development of advanced in vitro culturing techniques has allowed the development of new products which combine human dermal cellular materials with those derived from animals (e.g., Epicel). These products involve the harvesting of human epidermal cells (either from the individual being treated or from donor tissue) which are then cultured with animal cells to produce sheets of biosynthetic skin which have been proposed for use in treating human skin conditions.

Plant Based

A product derived from plant sources (for example VersaWrap).

Synthetic Products

Synthetic treatments include various forms of skin-like coverings, barriers, and devices to augment cartilage and other connective tissues. This category includes wound dressings, silicone/nylon membranes and material to augment or replace cartilage, tendons, and ligaments.

Completely synthetic wound dressings and other grafting products (e.g., Biobrane) are composed of manufactured materials to form a covering for wounds. This type of product may consist of a wide array of materials including silicone, nylon, polypropylene, and polyester.

Xenographic and Xenographic-Related or Derived Products

Many wound care and reconstructive products are made from materials derived from various animal sources including cow, horse, and pig tissues. Most of these products are created by harvesting living tissues (e.g., skin, intestines, tendons, etc.) from a donor animal, which are then processed to remove the cellular content and leave only the collagen protein scaffold. As with such allogeneic products, this scaffold is intended to function as a welcoming environment into which new autologous cells (e.g., skin, tendon, and cartilage) may grow. Most xenographic products are composed of the decellularized collagen scaffold alone (e.g., Collamend, Cuffpatch, Mediskin, Oasis, OrthoADAPT, Pelvicol, Pelvisoft, PriMatrix, Surgisis, Unite).

Xenographic materials have been proposed for many applications including reconstruction procedures of the breast, pelvic floor, abdominal wall, tendons, and others. These products are sewn onto the soft tissues where they are needed to provide support and strengthen the underlying structures. This occurs by the xenograft acting as a bed for new growth of autologous tissue.

Another type of product is a substance made by or derived from xenographic sources. One such product is honey, which has been proposed as a topical treatment for a wide variety of skin conditions.

Diabetic foot ulcer (DFU): A potential complication of diabetes due to prolonged elevated blood sugar levels which can damage blood vessels and nerves throughout the body. A DFU is a slow healing full-thickness wound, through the dermis, below the ankle on a weight-bearing or exposed surface in an individual with diabetes. DFUs are categorized as being neuropathic, ischemic, or neuroischemic (mixed). The most common sites are the plantar surface of foot and the toes. DFUs are caused by repetitive injury to an insensate or vascularly compromised foot and may lead to amputation.

Epidermolysis bullosa (EB): A disease characterized by the presence of extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma.

Equine-derived decellularized collagen products (e.g., OrthADAPT and Unite): This is a type of product derived from purified tissues which are derived from horses. It has been proposed that this type of technology may be used for the repair and reinforcement of soft tissues such as tendons and ligaments, as well as the treatment of skin wounds.

Frey’s Syndrome: A condition occurring in some individuals after removal of the parotid salivary gland, in which nerve damage results in flushing and sweating on one side of the face when certain foods are consumed.

Hernia meshes of non-biologic origin: These products are either synthetic or biosynthetic:

Biosynthetic: Mesh products are made from resorbable synthetically derived meshes with resorption profiles between 6 and 36 months. Theoretically, this allows native collagen deposition for wound strength and durability while reducing the risks of chronic mesh infection affiliated with permanent synthetic alternatives.
Synthetic: Mesh products are made from either woven extruded monofilament (for example, polypropylene or polyester) or created from expanded polytetrafluoroethylene. They may be subcategorized by; weight/density, material, composition, pore characteristics, and mechanical parameters. Products in this category are permanent and are not absorbed by the body.

Nerve conduits: A bioengineered product used in the repair of traumatic peripheral nerve injuries. The product is used in the reconstruction of a gap defect by placing proximal and distal nerve stumps into a tubular construct. Conduits are intended to replace the need for nerve autograft harvest.

Nerve wraps: A bioengineered sheet of material used in the repair of traumatic peripheral nerve injuries. The product is formed into a tube around approximated nerve stumps, it’s purpose is to minimize fibrosis and scarring, and provide a narrow gap to facilitate bridging across the repair site.

Standard hernia repair: A surgical procedure that is done to treat bulges of organ or intra-abdominal tissue through a weakness in the abdominal wall (hernias) when they are relatively small in size, technically simple to repair, and at low risk for complications. The procedure repairs the local defect and supports the weakened abdominal wall. The procedure can be done via laparoscopic approach and may use synthetic, biological or composite mesh to reinforce the abdominal wall.

Vancouver scar scale: An objective and validated method for describing burn scars that includes a summation of scar characteristics including pigmentation [0-2], vascularity [0-3], pliability [0-5], and height [0-3], normal skin is given a score of 0 for each category.

Wound infection: A wound with at least some clinical signs and symptoms of infections such as increased exudates, odor, redness, swelling, heat, pain, tenderness to touch, and purulent discharge; quantitative culture is not required.

1. FDA In Brief: FDA Warns About Differing Complication Rates for Acellular Dermal Matrix, a Type of Surgical Mesh, Used in Implant-Based Breast Reconstruction. March 31, 2021. Available at: https://www.fda.gov/news-events/fda-brief/fda-brief-fda-warns-about-differing-complication-rates-acellular-dermal-matrix-type-surgical-mesh#:~:text=Today%2C%20the%20U.S.%20Food%20and,with%20the%20use%20of%20ADM. Accessed on February 13, 2025.
2. National Library of Medicine (NIH). Burns. Last updated October 10, 2024. Available at: https://medlineplus.gov/burns.html. Accessed on February 13, 2025.
3. National Library of Medicine (NIH). Diabetic Foot. Last updated March 15, 2024. Available at: https://medlineplus.gov/diabeticfoot.html. Accessed on February 13, 2025.

Bilaminate Skin Substitute
Culture-Derived Human Skin Equivalent
Frey’s Syndrome
Graves’ Disease
Human Skin Equivalent
Wound Healing
Xenograft

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

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