Tissue-engineered skin is a significant advance in the field of wound healing and was developed due to limitations associated with the use of autografts. Blood-derived growth factors are also being investigated as an aid in wound healing. This document addresses the use of skin substitutes and growth factors in wound healing and surgical procedures.

For the purposes of this document the following terms are defined as below:

• Autologous: A product derived from the individual's own body or body products.
• Allogeneic: A product derived from humans, other than the individuals themselves.
• Xenographic: A product derived from non-human organisms (e.g., Cows, pigs, horses, etc.)
• Synthetic: A product derived from man-made materials.
• Composite: A product derived from a mix of materials of various origins.

Note: The use of non-engineered allogeneic cadaver-derived skin grafts is not addressed in this document

Note: This document does not address the use of meshes or patches of non-biologic origin when used for standard hernia repair procedures.

Note: For more information regarding breast procedures please see:

• SURG.00023 Breast Procedures; including Reconstructive Surgery, Implants and Other Breast Procedures.

Note: For information regarding the use of grafting in knee surgery procedures, please see:

• TRANS.00015 Meniscal Allograft Transplantation of the Knee

Note: for information regarding the use of mesenchymal Stem cells, please see:

• TRANS.00035 Mesenchymal Stem Cell Therapy For Orthopedic Indications

I.   Synthetic Products

Medically Necessary: 

The use of recombinant human platelet-derived growth factor (i.e., becaplermin [Regranex^®]) is considered medically necessary when it is used as an adjunct to standard wound management for either of the indications (1 or 2) below:

1. When used according to the U.S. Food and Drug Administration (FDA) labeled indication for individuals with neuropathic diabetic ulcers extending into the subcutaneous tissue or beyond.  In addition, candidates for becaplermin gel for treatment of neuropathic ulcers should meet ALL of the following criteria:
   1. Adequate tissue oxygenation, as measured by a transcutaneous partial pressure of oxygen of 30 mm Hg or greater on the foot dorsum or at the margin of the ulcer; and
   2. Full-thickness ulcer (i.e., Stage III or IV), extending through dermis into subcutaneous tissues; and
   3. Participation in a wound management program, which includes sharp debridement, pressure relief (i.e., non-weight-bearing), and infection control.
      or
2. As a treatment of pressure ulcers extending into the subcutaneous tissue. In addition, candidates for becaplermin gel for treatment of pressure ulcers should meet ALL of the following criteria:
   1. Full-thickness ulcer (i.e., Stage III or IV), extending through dermis into subcutaneous tissues; and
   2. Ulcer in an anatomic location that can be offloaded for the duration of treatment; and
   3. Albumin concentration greater than 2.5 dL; and
   4. Total lymphocyte count greater than 1,000; and
   5. Normal values of vitamins A and C.

Note: Individuals are typically treated once daily for up to 20 weeks or until complete healing occurs with becaplermin.

Investigational and Not Medically Necessary: 

The use of recombinant human platelet-derived growth factor (becaplermin/Regranex^®) is considered investigational and not medically necessary for all other applications not listed above as medically necessary, including, but not limited to, the following:

• Ischemic ulcers;
• Venous stasis ulcers;
• Ulcers that do not extend through the dermis into subcutaneous tissue.

Antimicrobial silver wound dressings, (e.g., Acticoat, Actisorb^™_, and Silversorb^®) therapy and dressings, are considered investigational and not medically necessary for all applications.

The use of synthetic Silicone/Nylon Membrane wound dressing (e.g., Biobrane^®) is considered investigational and not medically necessary for all applications.

The use of synthetic fistula plugs (e.g., GORE BIO-A^® Fistula Plug) is considered investigational and not medically necessary for all applications.

The use of synthetic soft-tissue grafting materials (e.g., SportMesh™) is considered investigational and not medically necessary for all applications.  Note: This document does not address the use of meshes or patches of non-biologic origin when used for standard hernia repair procedures.

II.   Autologous Products

Investigational and Not Medically Necessary:

Autologous blood-derived wound products, (e.g., Autologel^™_, SafeBlood^™_, Vitagel^®) are considered investigational and not medically necessary for all applications.

The use of platelet rich plasma (PRP) is considered investigational and not medically necessary for all indications, including the treatment of any of the following

• Cutaneous wounds
• Soft tissue injuries (including epicondylitis and sinus surgery)
• Bone injuries (including surgically created wounds and non-unions)

III.   Allogeneic Products

Medically Necessary:

Alloderm^® is considered medically necessary for the following:

• Breast reconstruction surgery
• Surgical repair of complex abdominal wall wounds (e.g., due to infection, fascial defect, etc.)

Apligraf^® is considered medically necessary when used for either of the following indications:

• In conjunction with standard therapeutic compression for the treatment of chronic, non-infected, partial or full-thickness skin ulcers due to venous insufficiency of greater than one month duration and which have not adequately responded following a one month period of conventional ulcer therapy (such as standard dressing changes, and standard therapeutic compression); OR
• In conjunction with standard diabetic foot ulcer care for the treatment of full-thickness neuropathic diabetic foot ulcers of greater than three weeks duration which have not adequately responded following at least a three week period of conventional ulcer therapy (such as surgical debridement, complete off-loading and standard dressing changes) and which extend through the dermis but without tendon, muscle, joint capsule, or bone exposure. 

Dermagraft^®_, an interactive wound dressing, is considered medically necessary when used for either of the following indications:

• The treatment of full-thickness diabetic foot ulcers of greater than six weeks duration that extend through the dermis, but without tendon, muscle, joint capsule, or bone exposure; OR
• When used on wounds with dystrophic epidermolysis bullosa.

OrCel^™_,, a composite skin substitute, is considered medically necessary in children with recessive dystrophic epidermolysis bullosa who are undergoing reconstructive hand surgery.

TransCyte^™_, a biosynthetic skin substitute, is considered medically necessary as a temporary wound covering to treat second and third degree burns.

Investigational and Not Medically Necessary:

Alloderm^® is considered investigational and not medically necessary for all other indications not listed above as medically necessary.

Apligraf^® is considered investigational and not medically necessary when used beyond five (5) applications for the medically necessary indications mentioned above.

Apligraf^® is contraindicated and consideredinvestigational and not medically necessary for:

1. Use on clinically infected wounds; or
2. In individuals with known allergies to bovine collagen; or
3. In individuals with a known hypersensitivity to the components of the Apligraf^® agarose shipping medium.

Dermagraft^® is considered investigational and not medically necessary for all other indications not indicated as medically necessary above, including but not limited to the treatment of infected ulcers and ulcers with sinus tracts.

The use of all other allogeneic human cadaver-derived decellularized skin products (e.g., Cymetra^®_, GraftJacket™, and Neoform Dermis™) is considered investigational and not medically necessary for any use, including, but not limited to the following indications:

1. Injection laryngoplasty; or
2. Prevention or treatment of post-parotidectomy gustatory sweating (Frey's Syndrome); or
3. Reconstructive surgery of the torso or abdomen; or
4. Repair of lower lid retraction in individuals with Graves' disease; or
5. Treatment of burns, either to treat the burn site or to treat an autograft donor site; or
6. Use in breast reconstruction or augmentation procedures.

C-QUR™ biosynthetic mesh is considered investigational and not medically necessary for all indications.

The use of cryopreserved allogeneic human skin (e.g., TheraSkin^®) is considered investigational and not medically necessary for all indications.

IV.      Xenographic and Xenographic-Related or Derived Products

Medically Necessary: 

Integra^™ Bilayer Matrix Wound Dressing, an artificial skin substitute, is considered medically necessary in the post-excisional treatment of full- thickness or deep partial-thickness burns when autografting is not feasible due to the individual's weakened physiological condition or a lack of suitable healthy tissue.

Investigational and Not Medically Necessary: 

Integra^™ Bilayer Matrix Wound Dressing is considered investigational and not medically necessary for all other applications not listed above as medically necessary.

The use of xenographic-related or derived products (e.g., MediHoney^®) is considered investigational and not medically necessary for all applications.

Xenographic wound treatment and tissue grafting products, including but not limited to the following products, are considered investigational and not medically necessary for all applications:

• Avaulta Plus™
• CellerateRX^®
• Collamend
• CorMatrix^®
• CRXa™
• Cuffpatch™
• ENDURAgen™
• E-Z Derm™
• Integra™ Matrix Wound Dressing
• Matristem^®
• Mediskin^®
• Menaflex™ Collagen Meniscus Implant
• Oasis™
• OrthADAPT™
• Pelvicol^®
• Pelvisoft^®
• Permacol™
• PriMatrix
• Strattice™
• SurgiMend^®
• Surgisis^® (including Surgisis^® AFP™ Anal Fistula Plug and Surgisis^® Gold™ Hernia Repair Grafts)
• TenoGlide™
• Unite™
• Veritas^® Collagen Matrix

V.    Composite Autologous / Allogeneic / Xenographic Products 

Investigational and Not Medically Necessary: 

The use of products made from a combination of human autologous and xenographic cellular materials (e.g. Epicel^®) is considered investigational and not medically necessary for all applications.

The use of products made from a combination of human allogeneic and xenographic cellular materials is considered investigational and not medically necessary for all applications.

I.   Synthetic Products

Recombinant platelet-derived growth factor (e.g., becaplermin gel) has been found to be efficacious as an adjunct to standard wound management for individuals with neuropathic diabetic ulcers and for the treatment of pressure ulcers. These conclusions are based on several well-designed randomized controlled studies. However, efficacy for other uses has not been demonstrated in the literature.

Antimicrobial silver wound dressings (e.g., Acticoat, Actisorb^™_, and Silversorb^®) have not been sufficiently evaluated in the peer-reviewed literature. It is not possible to determine their efficacy as a dressing to facilitate wound care because of the limited availability of clinical data. Further investigation with greater numbers of subjects in a larger number of centers and in different phases of wound care is needed.

Data regarding the use of synthetic Silicone/Nylon Membrane wound dressing (e.g., Biobrane^®) has been described in four separate randomized controlled trials (RCTs) in peer-reviewed published medical journals (Lal, 2000; Barret, 2000, Feldman, 1991; Gerding, 1990).  While all of these studies found that in comparison to their various control groups, the use of Biobrane significantly improved pain scores and healing times, unfortunately all of these studies involved small numbers of participants and were not conducted in a blind fashion.  Further data are required to allow a thorough assessment of the efficacy of this technology.

Synthetic products are now available on the market to treat anal and other fistulas (e.g., GORE BIO-A^® Fistula Plug).  However, there is currently insufficient data presented in the peer-reviewed published literature to demonstrate clinical efficacy. 

Synthetic products have recently been made available for the repair of soft-tissue injuries and other conditions (e.g., SportMesh™).  Such materials have been proposed as an alternative to autologous, allogeneic, and xenographic materials to repair, support or replace soft tissues.  The available evidence addressing such products is currently insufficient to allow adequate assessment of their efficacy and safety.

II.   Autologous Products

At this time, there are no published peer-reviewed articles addressing the use of autologous blood-derived wound products, (e.g., Autologel™, SafeBlood™, or Vitagel^®) in which it could be determined that any of the currently marketed products was used.  It is important that this information be known when assessing the efficacy of distinct types of autologous platelet-derived wound-healing preparations.  Therefore, conclusions regarding the efficacy of these preparations cannot be reached.

Platelet rich plasma (PRP) has been available for several decades and its use has been proposed for a wide variety of medical conditions.  The medical literature currently lists dozens of studies addressing the use of PRP for a wide variety of indications including chronic skin wounds, maxillofacial and sinus surgery, various musculoskeletal injuries and surgical procedures, endovascular surgery, plastic surgery, and thoracic and cardiac surgery.  Unfortunately, most available studies are small, uncontrolled, retrospective, and/or have short follow-up periods, constituting significant methodological flaws which limit their utility in evaluating the benefits of PRP use. 

Peerbooms and others published the only available RCT describing the use of PRP.  In this study 100 subjects with chronic lateral epicondylitis were randomly assigned to receive a single injection of PRP (n=51) or corticosteroids (n=49). After one year, 25 of the 49 subjects (51%) in the corticosteroid group and 37 of the 51 (73%) in the PRP group were deemed "successful" with greater than 25% reduction in DASH Outcome Measure scores (p=0.005).  The authors note that further study of the use of PRP is warranted.

One area which has seen a significant interest in the use of PRP is orthopedics.  Within this specialty PRP has been investigated for the treatment of a large number of conditions, including long bone non-unions (Calori 2008; Mariconda, 2008), epicondylitis (Edwards, 2003; Mishra, 2006), total knee replacement (TKR) surgery (Berghoff, 2006; Gardner, 2007; Everts, 2007), and others.  As stated above, these studies have small sample sizes and other serious design flaws which prevent the conclusions from being more widely generalized to clinical practice.  Additionally, many of these studies conclude that there is little, if any, benefit to the use of PRP.  One exception to this is the use of PRP during TKR, where the majority of studies reported significant benefits with regard to improving post-operative blood loss, length of stay and pain ratings.  However, most of these small studies recommended the performance of larger studies to verify and confirm these findings.

PRP has also been extensively studied in neurosurgery, especially spinal fusion.  Several small randomized controlled trials have been published investigating the use of PRP for improving fusion rates (Carreon, 2005; Feiz-Erfan, 2007; Hee, 2003; Weiner; 2003), none of which reported any significant benefit from PRP use.

Overall, the body of data regarding potentially beneficial use of PRP for any condition is of poor quality and of limited use.  Large well-designed trials are needed to effectively evaluate the use of PRP in the clinical setting.

III.   Allogeneic Products

Human-derived composite cultured skin (e.g., Apligraf^® Dermagraft^® OrCel^™_, and TransCyte^™) has been proposed for the treatment of burns and other skin wounds.  There are several products available on the market at this time, and they are sufficiently different in their manufacture and origin that they cannot be addressed as equivalent products.

The results of randomized controlled, multicenter studies support that Apligraf interacts with the individual's own cells, responds to individual wound characteristics, and promotes healing of venous leg ulcers more effectively and faster than compression alone. Further studies are underway to investigate the use of Apligraf for the treatment of pressure sores, dermatological surgery wounds and burns. At this time, there is insufficient information to extend coverage for the use of Apligraf in the treatment of these conditions.

The results of randomized controlled, multicenter studies support that Dermagraft is efficacious for the treatment of diabetic foot ulcers. However, label warnings and precautions indicate that Dermagraft is contraindicated for use in ulcers that have signs of clinical infection or in ulcers with sinus tracts. Dermagraft was granted an FDA Humanitarian Device Exemption (HDE 2002) for the treatment of dystrophic epidermolysis bullosa. Additional clinical trials are needed to investigate the safety and effectiveness of this product for other applications.

OrCel is a living skin equivalent (composite cultured skin) that was granted an FDA Humanitarian Device Exemption (HDE) in 2001 for use in children with recessive dystrophic epidermolysis bullosa (RDEB), who are undergoing reconstructive hand surgery. However, there is still little clinical data to support its use in other applications. Additional multicenter clinical trials are underway to investigate the effectiveness and tolerability of this product.

TransCyte has been found to be as efficacious as human cadaver skin, when used as a temporary wound covering to treat second and third degree burns. This conclusion is supported by well-designed randomized, multicenter studies.

The use of allogeneic human-derived decellularized skin (e.g., Alloderm®, GraftJacket™, and Neoform Dermis™) has been investigated as a treatment for a wide variety of applications, including wound treatment and in surgical procedures.  As with human-derived composite cultured skin discussed above, there are several products available on the market at this time.  Again, these products are sufficiently different in their manufacture that they cannot be addressed as equivalent products.

There are over a dozen small case series reports published in the peer-reviewed medical literature describing the use of Alloderm^® to partially or completely enclose an implanted breast prosthesis during post-mastectomy breast reconstruction.  The goal of this procedure is to reduce complications related to contracture, periprosthetic atrophy, and development of thin capsules.  The results provided in these case series studies indicate good symmetry, increased soft tissue padding, and decreased rippling and implant visibility.  While the available data is limited regarding the long-term benefits and outcomes of this procedure, it has become a widely used and accepted method of breast reconstruction.  Expert opinion of breast surgeons supports the use of Alloderm for this indication.

The treatment of infected or contaminated abdominal wall wounds and defects is difficult.  Standard fascial prostheses such as polypropylene and polyester mesh, which are routinely used for non-complex cases, may exacerbate wound infection, fistula and adhesion formation, and erosion, leaving few real options for such individuals.  The use of Alloderm for the treatment of complex abdominal wall wounds has been reported in over thirty peer-reviewed journal articles.  These studies demonstrate a high rate of successful wound healing with relatively low numbers of complications.  As with the use of Alloderm and breast reconstruction, the use of Alloderm for complex abdominal wall wounds has been widely used and accepted treatment method, although data is limited regarding the long-term benefits and outcomes of this use.  Expert opinion of surgeons who routinely treat these types of wounds support the use of Alloderm for this indication.

At this time there is limited data addressing the use of Alloderm for use in treating chronic wounds.  There is very limited evidence available regarding the use of Alloderm in the treatment of burns or for surgically created wounds such as in the treatment of lid retraction in individuals with Graves' disease or in the prevention of Frey's Syndrome.  Additionally, Alloderm has been proposed for use in a wide variety of surgical applications, including breast reconstruction and other chest and abdominal procedures.  There are no existing large-scale randomized trials for the use of Alloderm for any of these proposed applications.  However, there is consensus among experts, based upon available smaller trials and personal experience, that the use of Alloderm for breast reconstruction and complex abdominal wall wounds is beneficial and improves health outcomes (Baxter, 2003; Becker, 2009; Bindingnavele, 2007; Breuing, 2005, 2007; Espinosa-de-los-Monteros , 2007; Gamboa-Bobadilla, 2006; Glasberg, 2006; Misra, 2008; Patton, 2007; Spear, 2008; ).

There are currently two studies available in the peer-reviewed literature addressing the use of Alloderm for treatment of burns. The first study involved 19 participants randomized to Alloderm with an autograft overgraft vs. Alloderm with an allograft overgraft which was replaced with an autograft overgraft after one week (Munster, 2001).  Graft uptake was not different between groups.  Immediate Alloderm with thin autograft was associated with more healing than spilt thickness grafts.  The second study involved 52 non-randomized participants all of whom received Alloderm covering to radial arm free flap donor sites. (Sinha, 2003)  The results of this study indicated that there were minimal contractures or restrictions to the healed graft.  While these studies suggest some benefit as to the use of Alloderm for burns, larger randomized trials are needed to confirm efficacy of this procedure.

In the one available clinical trial of Alloderm in people with lid retraction due to Graves' disease, only 14 participants were studied in a non-blinded fashion (Sullivan, 2003).  While the findings of this study were promising, further controlled studies with larger numbers of participants are needed to confirm the efficacy of this procedure. 

At this time there are two available studies in the peer-reviewed literature regarding the use of Alloderm to treat Frey's syndrome.  The first involved 64 participants randomly assigned to the use of Alloderm placement in the parotid bed following removal of the parotid gland vs. no Alloderm (Govindaraj, 2001).  While the rate of gustatory sweating in the Alloderm group was found to be statistically lower than the control group, the Alloderm group also had an almost 3-fold increase in complications, including both a higher frequency of seroma as well as one wound infection.  In a second study 30 participants were randomized into three groups; 1) superficial parotidectomy with placement of Alloderm, 2) superficial parotidectomy without placement, and 3) deep-plane rhytidectomy. (Sinha, 2003)  The incidence of both subjective and objective Frey's syndrome was significantly higher in group 2 when compared to both groups 1 and 3. However, given the small numbers of subjects in each group, the results of this study do not allow strong conclusions to be drawn as to the effectiveness of this procedure.

Cymetra^®_, an injectable micronized particulate form of Alloderm, has been proposed as a minimally invasive tissue graft product.  At this time, there are only three peer-reviewed published articles addressing the use of this product.  All these studies involve participants with vocal cord paralysis.  One study by Morgan and colleagues (2007) was a retrospective non-randomized controlled trial involving 19 participants undergoing injection laryngoplasty with Cymetra or medialization laryngoplasty.  The authors reported no significant difference between groups.  The follow-up time was 3 months.  No long-term comparison data was provided.  Another report of a retrospective case series study involving 10 participants all receiving 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 eight participants (40%) were found to have lasting benefit.  Finally, Karpenko and others (2003) reported the results of a small (n=10) case series study.  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.

The current body of evidence available in the peer-reviewed medical literature addressing the use of GraftJacket^® is limited to a few small studies.  One randomized controlled trial compared the use of standard surgical debridement followed by GraftJacket placement vs. standard surgical debridement alone (Brigido, 2004).  The findings of the study found significant differences between the two groups, with the experimental group demonstrating much faster healing progression.  While the results of this study are promising, the small sample size (20 participants in each group) as well as its single-blind design, limit its utility.  A second randomized controlled trial involved 86 subjects with diabetic foot ulcers (Reyzelman, 2009).  The authors reported significantly better complete and mean healing times in the GraftJacket group (69.6% and 5.7 weeks) compared to the controls (46.2% and 6.8 weeks), who received standard care (p= 0.029).  Furthermore, there was significantly higher non-healing rate for the control group (53.9%) compared with the study group (30.4%) at 12 weeks (P=0.015).  Further studies with larger populations are warranted to better evaluate the efficacy of this procedure.

C-QUR™ biosynthetic mesh has been proposed for use in abdominal surgical repair procedures.  At this time there are no peer-review published studies available describing this product or its use in human subjects.  Further information is required to fully evaluate the use of this product in the clinical setting.

The use of Theraskin cryopreserved human skin allograft has only been described in one study (Landsman, 2010).  This is a single-center, retrospective, uncontrolled case series study of 188 subjects with venous leg ulcers and diabetic foot ulcers.  The authors used historical controls for comparison, many studies of which are RCTs. The follow-up time was only 20 weeks.  While the authors report favorable results, this study is insufficient to demonstrate the safety or efficacy of Theraskin.

IV.      Xenographic Products

The use of products comprised of bovine-tendon collagen, glucoseaminoglycan and silicone (e.g., Integra^™ Bilayer Matrix Wound Dressing) has been found to be efficacious in the post-excisional treatment of full-thickness or deep partial-thickness burns when autografting is not feasible. This conclusion is supported by well-designed randomized, multicenter studies.  However, efficacy has not been demonstrated in the literature for other uses.

Bovine-derived decellularized skin products (e.g., PriMatrix^™ or TissueMend^®) have been proposed for the treatment of skin wounds.  At this time there is no data published in the peer-reviewed literature addressing the effectiveness of this type of product in humans.

Bovine-derived tendon collagen and glycosaminoglycan (e.g., Integra^™ Matrix Wound Dressing) is a type of wound care device comprised of a porous matrix of cross-linked bovine tendon collagen and glycosaminoglycan.  At this time there are no peer-reviewed published studies regarding the efficacy of this device in the clinical setting.  Such data is needed for an appropriate evaluation of this technology.

The use of equine-derived decellularized collagen products (e.g., OrthADAPT™ and Unite™) has not been adequately studied, as demonstrated by the lack of any peer-reviewed published literature on the subject.  

There is currently no peer-reviewed published data regarding the use of porcine-derived polypropylene composite wound dressing (e.g., Avaulta Plus™) in the clinical setting in human subjects. Until comparative studies of this technology have been made available, a thorough evaluation of the safety and efficacy cannot be completed. 

The use of porcine-derived decellularized collagen products (e.g., Collamend, Cuffpatch™, Pelvicol^®_, Pelvisoft^® and Strattice™) has been proposed for use in a wide variety of surgical procedures and in the treatment of skin wounds.  The available evidence in the form of peer-reviewed published clinical trial data is insufficient to allow for proper assessment regarding the efficacy of this technology.

The use of  porcine-derived decellularized intestinal mucosa products (e.g., Oasis™, and Surgisis^® [including Surgisis AFP™ Anal Fistula Plug]) has been investigated for the treatment of both chronic wounds, such as anal fistula and skin ulcers, as well as for surgical wounds. 

At this time, there are a large number of case series studies published on the use of the Surgisis anal fistula plug (Champagne, 2006; 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.   Two studies have reported on the results from non-randomized controlled retrospective trials.  Ellis and colleagues describes the results of a study that involved 95 control subjects who had transsphincteric or rectovaginal fistulas repaired via advancement flap repair (2007).  The experimental group included only 18 subjects who received treatment with Surgisis.  The results indicated a significant benefit to the Surgisis procedure.  Another study included 80 subjects 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.  

There has been one randomized controlled trial addressing the use of Surgisis anal fistula plug.  This study reported by Ortiz et al. involved 43 subjects 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 one 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. Finally, two large non-randomized controlled trials have been published addressing the use of Surgisis.  Chung and colleagues (2009) reported on the results of a retrospective study that involved 245 subjects 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.  The second study by Hyman and others involved 245 subjects (2009) 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 (3).  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.

At this time there are only three peer-reviewed published studies addressing the use of Oasis-brand porcine-derived decellularized intestinal mucosa.  The first was published by Mostow and colleagues (2005), and they describe a randomized controlled trial (RCT) involving 62 participants who received Oasis and compression therapy for venous stasis leg ulcers.  The control group of 58 participants received compression therapy alone.  The authors reported significantly better healing rate of the Oasis group over the control group at 12 weeks.  The next publication described an RCT involving individuals with diabetic foot ulcers (Neizgoda, 2005).  The experimental group included 37 participants who were treated with the Oasis graft and 36 who were treated with Regranex gel.  As with the previously described trial, the authors reported significantly improved results with the Oasis graft.  Finally, the third trial by Romanelli (2007) describes a study comparing Oasis against a product not currently available in the U.S., Hyaloskin.  The result of this trial while favorable to Oasis, is not particularly useful in the evaluation of Oasis.  The scientific literature of the comparison technology is even sparser than that for Oasis.  Therefore the comparison of the two products does not add significantly to what is known about Oasis in comparison to other more widely used treatments. 

The available evidence addressing the use of E-Z Derm^™ brand porcine-derived decellularized fetal skin is limited to two small trials from over a decade ago (Vanstraelen, 1992; Healy, 1989).  While both of these studies are controlled trials, they are hampered by small numbers of participants (20 and 32 respectively).  The Vanstraelen study concluded that hypertrophic scarring occurred in 25 per cent of xenograft-dressed sites, but none was seen in the comparison group.  In addition, several allergic reactions were reported to the porcine xenograft.  The conclusions of the Healy study found in comparison to burned participants treated with Jelonet, individuals treated with E-Z Derm did not vary significantly in terms of bacterial colonization rate, need for surgical treatment, and time for spontaneous healing, analgesic requirements or frequency of dressing changes.  Data from more recent trials is not available.

There are currently no published studies addressing the use of Mediskin^® brand porcine-derived decellularized fetal skin.  No conclusions can be drawn regarding this product's efficacy in the clinical setting.

Collagen meniscus implants (e.g., Menaflex™) have been proposed as a treatment method for individuals with a damaged knee meniscus.  At this time there is only one large trial of this type of procedure (Rodkey, 2008).  This study involved 311 subjects 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 fifty-nine months (range, sixteen to ninety-two months).  Repeat arthroscopies done in the experimental group at one 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.  While this study does show that there is some potential benefit to the use of meniscal collagen implants in some populations, further data is warranted to further understand the clinical implications of this technology.

The use of xenographic-related or derived products has been proposed for the treatment of a wider variety of conditions.  At this time the most studied of these types of products is the use of honey (e.g., MediHoney^®) for 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, most addressing the treatment of venous leg and foot ulcers.  Jull and colleagues published the largest of these trials, which included 368 subjects randomized to receive treatment with either calcium alginate dressing impregnated with manuka honey or usual 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 subjects 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 not significant differences between groups in other primary endpoints.  The other most studied condition addressed in the literature is the treatment of burns.  The largest study currently available involved 150 subjects randomized to receive treatment with either silver sulphadiazine (SSD) or honey (Malik, 2010).  Each subject acted 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 that SSD sites (21 days vs. 24 days, p < 0.0001). 

At this time the evidence addressing the use of honey for skin wounds is lacking.  The current studies are mostly small, unblinded controlled studies, but the choice of controls used has a great variety, making the effectiveness of comparing study outcomes difficult.  Further investigation with large well-done blinded trials using standardized controls is warranted.

IV.      Composite Autologous / Allogeneic / Xenographic Products

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 which are then cultured with animal cells to produce sheets of biosynthetic skin which have been proposed for use in treating human skin conditions.  At this time there are no peer-reviewed published articles addressing such products.

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 wounds that have failed to heal despite conservative measures, referred to as chronic wounds, pose 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 graft 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, from 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).

Synthetic Products

Synthetic treatments include various forms of skin-like coverings and barriers, including antimicrobial silver wound dressings, silicone/nylon membranes, and even growth factors manufactured in a laboratory using recombinant human DNA technology. 

Antimicrobial silver wound dressings (e.g., Acticoat, Actisorb, Silversorb) involve a synthetic layer of nylon, rayon etc. coated with silver nanocrystals.  It has been proposed that such coatings act as a barrier to infectious agents and kill bacteria before they are able to reach the wound.

Completely synthetic wound dressings (e.g., Biobrane) are composed of man-made materials to form a complex multilayer covering for wounds. This type of product may consist of a wide array of materials including silicone, nylon, and others, as well as collagen or other biologic materials.

Human platelet-derived growth factors (PDGF) (e.g., Regranex) are produced from genetically-engineered yeast cells, into which the recombinant human form of the gene for the B-chain of PDGF has been inserted.  The yeast cells read the inserted genes, as if they were their own and produce PGDF as a product of their metabolism.  The PGDF is then collected and purified for use in clinical care.  It must be noted that on June 6, 2008 the FDA required the following black box warning be placed on the label of Regranex:

"An increased rate of mortality secondary to malignancy was observed in patients treated with 3 or more tubes of REGRANEX Gel in a post-marketing retrospective cohort study. REGRANEX Gel should only be used when the benefits can be expected to outweigh the risks. REGRANEX Gel should be used with caution in patients with known malignancy."

Autologous Products

Autologous wound care treatment may include a skin graft, which is a piece of skin from another site on the individual's body moved to the wound site.  This method is frequently the preferred treatment, however, this method actually creates a new wound at the site where the graft was harvested, adding to the risk of infection and other complications. 

Platelet rich plasma (PRP) is a substance derived from an individual's own blood, after high-speed centrifugation.  It functions by re-creating the final phase in normal blood coagulation that produces a fibrin clot, adhering to the application site and providing wound coverage and stabilization.  Additionally, PRP may increase the concentrations of beneficial healing factors within the application site, also potentially augmenting the healing effect.  PRP's other proposed benefits include that is it autologous and thus not immunoreactive, it is absorbable, and it is fairly simple to produce.  Research in various potential uses for PRP has been ongoing, including wound care, burns, orthopedics, maxillofacial surgery, plastic surgery, and others.   

Another autologous method involves products derived from the individual's own blood growth factors, which are collected from the blood (e.g., Autologel, SafeBlood).  To make these types of products, blood is drawn from the individual and is centrifuged at high speeds to separate the blood components from one another.  The platelet rich plasma portion of the blood is activated with various reagents to convert the blood protein fibrinogen into fibrin, one of the major components required to form a blood clot.  This fibrin-rich gel-like substance is then immediately applied to the wound to form a wound covering.

Vitagel^® is a product that uses an individual's own blood mixed with microfibrillar collagen and thrombin to create an artificial scab on wounds.  It has been proposed that this product may assist in controlling bleeding during operative procedures and other circumstances where bleeding may be of concern.

Allogeneic Products

There are a currently two different types of allogeneic (human derived) wound care products available.  The first 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. 

The other allogeneic products are composite products that may contain human skin cells, keratinocytes and/or fibroblasts (depending upon the product), derived from newborn foreskins which are imbedded into a decellularized collagen protein scaffold derived from either cows or pigs (e.g., Apligraf, OrCel).  Some of these products may also consist of layers of synthetic materials like silicone, nylon, or polyglactin (e.g., Dermagraft, TransCyte).

Xenographic and Xenograhic-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 that is then processed to remove the cellular content to leave only the collagen protein scaffold.  As with such allogeneic products, this scaffold is intended to act as a welcoming environment into which new autologous cells (e.g., skin, tendon, cartilage) may grow.  Xenographic products may be composed of only the bare collagen scaffold (e.g., Mediskin, Oasis, PriMatrix) or may be combined with synthetic materials to create a composite product (e.g. Avaulta Plus, Integra matrix, Integra Bilayer Matrix). 

Another type of product involves the use of 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.

Composite Autologous / Allogeneic / Xenographic Products

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. 

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 hernia 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 instances, the use of either grafting materials has been suggested as an alternative to a surgical approach. One example of this is in the case of injection laryngoplasty, which has been proposed as an alternative to medialization laryngoplasty.

Xenographic materials have been proposed for many such applications including reconstruction procedures of the breast, pelvic floor, abdominal wall, tendons and others.  These products are usually made from the decellularized collagen scaffold alone (e.g., Collamend, Cuffpatch, Pelvicol, Pelvisoft, Surgisis, OrthoADAPT, Unite) and are sewn onto the soft tissues where they are needed where they have been proposed to provide support and strengthen the underlying structures.

Antimicrobial silver wound dressing (e.g., Acticoat, Actisorb^™_, and Silversorb^®): A technology proposed for the prevention of wound adhesion, limit nosocomial (hospital) infections, control bacterial growth, and facilitate burn wound care through a silver-coated dressing material.  It consists of layers of a silver-coated synthetic mesh.

Allogeneic: A product derived from humans, other than the individual themselves.

Autologous: A product derived from the individual's own body or body products.

Bovine-Derived Decellularized Fetal Skin Products (e.g., PriMatrix^™ or TissueMend^®): This type of product is an acellular dermal matrix composed of fetal bovine dermis.  Proposed for the treatment of skin wounds as well as for the repair and reinforcement of soft tissues where weakness exists, such as for repair of the supraspinatus tendon of the rotator cuff.

Bovine-derived tendon collagen and glycosaminoglycan products (e.g., Integra^™ Matrix Wound Dressing): This is a wound care product comprised of a porous matrix of cross-linked bovine tendon collagen and glycosaminoglycan.  The collagen-glycosaminoglycan matrix provides a scaffold for cellular and capillary growth.

Bovine-derived tendon collagen, glucoseaminoglycan and silicone (e.g., Integra^™ Bilayer Matrix Wound Dressing): This type of product consists of a bilaminar membrane with a porous lattice of purified bovine collagen that acts as the dermis with a layer of silicone rubber or silastic that acts as a temporary epidermis.

Composite: A product derived from a mix of materials of various origins.

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 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.

Growth factors: Are products that play important roles in the regulation of cell division and tissue propagation.

Human-derived autologous wound factor gel (e.g., Autologel^™ and SafeBlood^™): This type of product is derived from blood taken from an individual to create a platelet-rich plasma preparation for the treatment of wounds.

Human-derived composite cultured skin (e.g., Apligraf^®_, Dermagraft^®_, OrCel^™_, and TransCyte^™): This type of product is a human skin equivalent produced from bovine collagen and skin cells derived from donor tissues.  It is proposed to temporarily provide wound protection and foster the growth of healthy new skin.

Human-derived decellularized skin (e.g., Alloderm^®_, Cymetra^®_, GraftJacket™, and Neoform Dermis™): This type of product is an acellular dermal matrix derived from donated human skin.  It is produced by processing donated human skin to remove cellular material that may trigger a tissue rejection reaction and is tested to reduce the likelihood of disease transmission.  This technology has been proposed for many applications, including treatment of skin wounds and in a variety of surgical procedures.

Human-platelet-derived growth factor gel [i.e., becaplermin (Regranex^®)]: This is a recombinant human form of platelet-derived growth factor (PDGF) that has been produced from genetically engineered yeast cells into which the gene for the PDGF has been inserted.  This product has been proposed for the treatment of chronic or non-healing wounds.

Platelet rich plasma: A preparation made of concentrated platelets from autologous blood, this substance has been suggested for improved healing for a wide variety of medical conditions.

Porcine-derived decellularized collagen (e.g., Collamend, Cuffpatch™, Pelvicol^®, and Pelvisoft^®): This is a type of product derived from purified tissues derived from pigs.  It has been proposed that this type of technology may be used in the surgical repair and reinforcement of soft tissues.

Porcine-derived decellularized intestinal mucosa (e.g., Oasis^™, and Surgisis^® [including Surgisis AFP™ Anal Fistula Plug]):  This type of product is an acellular graft material derived from pigs, it has been proposed to facilitate healing when sutured into wounds or applied to a wide range of skin wounds.

Porcine-derived non-decellularized fetal skin (e.g., E-Z Derm^™): This type of product is made from pig tissue which is treated to decrease the likelihood of infection or immune reactions.  It is intended to treat skin wounds.

Porcine-perived polypropylene composite wound dressing (e.g., Avaulta Plus™): This type of product is made from pig tissue in conjunction with synthetic materials; it is intended to treat skin wounds.

Synthetic silicone/nylon membrane (e.g., Biobrane^®): This type of product is made from synthetic materials.  It is intended to treat skin wounds by providing a barrier to moisture loss and infection.

Synthetic: A product derived from man-made materials.

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.

Xenographic: A product derived from non-human organisms (e.g., cows, pigs, horses, etc.).

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. 

Wound healing products 

When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When services are also Investigational and Not Medically Necessary:

Application of skin substitutes and soft tissue grafts: 

When services may be Medically Necessary when criteria are met

Allogeneic Products 

When services may be Medically Necessary when criteria are met [for Apligraf, OrCel, TransCyte, and Dermagraft]:

When services may be Medically Necessary when criteria are met [for Alloderm]:

When services are Investigational and Not Medically Necessary
For the procedure codes listed above when criteria are not met, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary

When services are also Investigational and Not Medically Necessary [all other allograft products]

Xenographic, Synthetic or Composite Products 

When services may be Medically Necessary when criteria are met [for Integra Bilayer Matrix Wound Dressing]:

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met; for all other diagnoses not listed, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When Services are also Investigational and Not Medically Necessary: 

Future ICD-10 coding (effective 10/01/2013)
A draft of ICD-10 Coding related to this document, as it might look today, is available for reference and comments at: Appendix 1: Future ICD-10 coding

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33. Epstein E. A controlled trial, LSE vs killed LSE, is needed. Arch Dermatol. 2000; 136(4):555-556.
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35. Everts PA, Devilee RJ, Oosterbos CJ, et al. Autologous platelet gel and fibrin sealant enhance the efficacy of total knee arthroplasty: improved range of motion, decreased length of stay and a reduced incidence of arthrofibrosis. Knee Surg Sports Traumatol Arthrosc. 2007; 15(7):888-894 
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Government Agency, Medical Society, and Other Authoritative Publications:

1. American Diabetes Association. Standards of Medical Care in Diabetes—2010. Diabetes Care. 2010; 32(Suppl 1):S11-S61. Available at: http://care.diabetesjournals.org/content/33/Supplement_1. Accessed on May 12, 2011.
2. Bergin SM, Wraight P. Silver based wound dressings and topical agents for treating diabetic foot ulcers. Cochrane Database Syst Rev. 2006;(1):CD005082
3. Centers for Medicare and Medicaid Services. Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd. Accessed on  May 12, 2011.
   • National Coverage Determination for Blood-Derived Products for Chronic Non-Healing Wounds. NCD #270.3. Effective July 23, 2004.
   • National Coverage Determination for Porcine Skin and Gradient Pressure Dressings. NCD #270.5. Effective date not posted.
   • National Coverage Determination for Services provided for the Diagnosis and Treatment of Diabetic Sensory Neuropathy with Loss of Protective Sensation (Diabetic Peripheral Neuropathy). NCD #70.2.1. Effective July 1, 2002
   • National Coverage Determination for Treatment of Decubitus Ulcers. NCD #270.4. Effective date not posted.
   • National Coverage Determination for Collagen Meniscus Implant. NCD #150.12. Effective July 6, 2010.
4. Jones JE, Nelson EA. Skin grafting for venous leg ulcers. Cochrane Database Syst Rev. 2007;(2):CD001737.
5. Storm-Versloot MN, Vos CG, Ubbink DT, Vermeulen H. Topical silver for preventing wound infection. Cochrane Database Syst Rev. 2010;(3):CD006478.

1. National Library of Medicine (NIH). Burns. Available at: http://www.nlm.nih.gov/medlineplus/burns.html. Accessed on May 12, 2011.
2. National Library of Medicine (NIH). Diabetic Foot. Available at:  http://www.nlm.nih.gov/medlineplus/diabeticfoot.html. Accessed on May 12, 2011.

Articoat
Actisorb™
Alloderm^®
AlloMax™
APC+
Apligraf^®
Autologel™
Autologous Platelet Gel
Avaulta Plus™
Becaplermin Gel (Trade Name Regranex^®)
Bilaminate Skin Substitute
Biobrane Bilayer Skin Substitute
Biodesign™
Blood-Derived Growth Factors
CellerateRX^®
Collamend
CorMatrix^®
CRXa™
C-QUR™
Cuffpatch™
Culture-Derived Human Skin Equivalent
Cymetra^®
Dermagraft^®
DermaMatrix^® 
Diabetic Ulcer
E-Z Derm™
Epicel^®
EpiDex^®
ENDURAgen™
FlexHD^®
Frey's Syndrome
Gammagraft™
Gore Bio-A^® fistula plug
GraftJacket™
Graftskin
Grave's Disease
Growth Factors for Wound Healing
HSE
Human Skin Equivalent Grafts
Integra™ Bilayer Matrix Wound Dressing
Integra™ Matrix
Lower Lid Retraction
Mediskin^®
Matristem^®
MediHoney^®
Menaflex™ Collagen Meniscus Implant
Neodermis™
Neoform Dermis™
NuCell™
Oasis ™
OptiMesh™
OrCel™
OrthADAPT™
Pelvicol^®
Pelvisoft^®
Permacol™
PDGF
Plasmax^®
Platelet-Derived Growth Factors
Platelet-Derived Wound Healing Formula
Platelet Rich Plasma (PRP)
PriMatrix™
Procuren^®
Promogran™
Puracol^®
Recombinant Platelet-Derived Growth factor
Regranex^®
SafeBlood™
Silversorb^®
SmartPReP^® platelet-rich plasma preparation system
Strattice™
Surgisis^®
SportMesh™
SurgiMend^®
Surgisis^® AFP™
TenoGlide™
Theraskin
TransCyte™
TissueMend^®
Unite™
Vitagel^®   
Veritas^® Collagen Matrix
Wound Healing
XenMatrix™
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.