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 patient's own body or body products.
• Allogeneic: A product derived from humans, other than the patients 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 patients 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  > 2.5 dL; and
   4. Total lymphocyte count > 1,000; and
   5. Normal values of vitamins A and C.
      
      Note: Patients 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.

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 applications.

Apligraf^® is contraindicated and considered investigational and not medically necessary for:

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

Dermagraft^® is contraindicated and consideredinvestigational and not medically necessary for 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 patients 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.

IV.  Xenographic 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 other xenographic wound treatment and tissue grafting products is considered investigational and not medically necessary for all applications, including but not limited to:

• Avaulta Plus™
• Collamend
• Cuffpatch™
• E-Z Derm™
• Integra™ Matrix Wound Dressing
• Mediskin^®
• Oasis™
• OrthADAPT™
• Pelvicol^®
• Pelvisoft^®
• PriMatrix
• Strattice™
• Surgimend^®
• Surgisis^® (including Surgisis AFP™ Anal Fistula Plug)
• Unite™

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 patients 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 patients and were not conducted in a blind fashion.  Further data are required to allow a thorough assessment of the efficacy of this technology.

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. 

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 prosthesis 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 patients.  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 patients 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 patients 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 patients, 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 patients with lid retraction due to Graves' disease, only 14 patients were studied in a non-blinded fashion (Sullivan, 2003).  While the findings of this study were promising, further controlled studies with larger numbers of patients 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 patients 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 patients 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 patients with vocal cord paralysis.  One study by Morgan and colleagues (2007) was a retrospective non-randomized controlled trial involving 19 patients 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 patients 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 patients (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 single study (Brigido, 2004).  This randomized controlled trial compared the use of standard surgical debridement followed by GraftJacket placement vs. standard surgical debridement alone.  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 patients in each group) as well as its single-blind design, limit its utility.  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 patients.  Further information is required to fully evaluate the use of this product in the clinical setting.

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, CuffpatchÔ, 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. 

Surgisis had been described in only a few peer-reviewed journal articles.  Two of these studies are small case series studies with 46 and 20 patients each (Champagne, 2006; O'Connor, 2006 respectively). The findings of these studies demonstrate successful closure rates between 80 and 85%. Another report by Ellis and colleagues describes the results of a non-randomized controlled retrospective trial (2007). The study involved 95 control patients who had transsphincteric or rectovaginal fistulas repaired via advancement flap repair. The experimental group included only 18 patients who received treatment with Surgisis.  The results indicated a significant benefit to the Surgisis procedure.  However, the unrandomized and retrospective study design and small numbers of patients in the experimental group mitigate the power of these findings.  Finally, another non-randomized, unblinded study compared the use of the Surgisis AFP device vs. fibrin glue for the repair of anal fistula (Johnson, 2006). Out of the 25 patients studied, 10 underwent treatment with fibrin glue, the remaining 15 were treated with Surgisis AFP.  In the glue group 60% of patients had persistent fistula at three months, compared to 13% of patients in the Surgisis group.  While the results of these studies are promising, further evidence from larger, longer-term randomized blinded trials is warranted.

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 patients who received Oasis and compression therapy for venous stasis leg ulcers. The control group of 58 patients 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 a RCT involving patients with diabetic foot ulcers (Neizgoda, 2005). The experimental group included 37 patients 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 burn patients treated with Jelonet, patients treated with E-Z Derm did not vary significantly in terms of bacterial colonization rate, need for surgical treatment, 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.

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 patients 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 patient'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 a patient'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 patient's own blood growth factors, which are collected from the patent's 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 a patient'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 patient 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 Products

Many wound care products are made from materials derived from various animal sources including cow, horse and pig tissues.  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 skin cells 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)

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 patient themselves

Autologous: a product derived from the patient'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 patients 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 a patient 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; this type of product 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^®)]: thisis 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-Derived 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.

Synthetic 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:

Autologous Products 

When services are Investigational and Not Medically Necessary:

Allogeneic Products 

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

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 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 [Graftjacket, Cymetra, Gammagraft, C-QUR]

Xenographic 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: 

Peer Reviewed Publications:

1. Allenet B, Paree F, Lebrun T, et al. Cost-effectiveness modeling of Dermagraft for the treatment if diabetic foot ulcers in the French context. Diabetic Metab. 2000; 26(2):125-132.
2. Barret JP, Dziewulski P, Ramzy PI, et al. Biobrane versus 1% silver sulfadiazine in second-degree pediatric burns. Plast Reconstr Surg. 2000; 105(1):62-65.
3. Baxter RA.  Intracapsular allogenic dermal grafts for breast implant-related problems. Plast Reconstr Surg. 2003; 112(6):1692-1696.
4. Becker S, Saint-Cyr M, Wong C, et al.  AlloDerm versus DermaMatrix in immediate expander-based breast reconstruction: a preliminary comparison of complication profiles and material compliance. Plast Reconstr Surg. 2009; 123(1):1-6. 
5. Berghoff WJ, Pietrzak WS, Rhodes RD. Platelet-rich plasma application during closure following total knee arthroplasty. Orthopedics. 2006; 29(7):590-598. 
6. Bindingnavele V, Gaon M, Ota KS, et al. Use of acellular cadaveric dermis and tissue expansion in postmastectomy breast reconstruction. J Plast Reconstr Aesthet Surg. 2007; 60(11):1214-1218.
7. Boyce ST. Skin substitutes from cultured cells and collagen-GAG polymers. Med Bio Eng Comput. 1998; 3(6):791-800.
8. Brem H, Balledux J, Bloom T, et al. Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing. Arch Surg. 2000; 135(6):627-634.
9. Breuing KH, Colwell AS. Inferolateral AlloDerm hammock for implant coverage in breast reconstruction. Ann Plast Surg. 2007; 59(3):250-255.
10. Breuing KH, Warren SM.  Immediate bilateral breast reconstruction with implants and inferolateral AlloDerm slings. Ann Plast Surg. 2005; 55(3):232-239.
11. Branski LK, Herndon DN, Pereira C et al. Longitudinal assessment of Integra in primary burn management: a randomized pediatric clinical trial. Crit Care Med. 2007; 35(11):2615-2623.
12. Brigido SA, Boc SF, Lopez RC. Effective management of major lower extremity wounds using an acellular regenerative tissue matrix: a pilot study. Orthopedics. 2004; 27(1 Suppl):s145-149.
13. Browne AC, Vearncombe M, Sibbald RG. High bacterial load in asymptomatic diabetic patients with neurotrophic ulcers retards wound healing after application of Dermagraft. Ostomy Wound Manage. 2001; 47(10):44-49. 
14. Browne AC, Sibbald RG. The diabetic neuropathic ulcer: an overview. Ostomy Wound Manage. 1999; 45(1A Suppl): 6S-22S.
15. Calori GM, Tagliabue L, Gala L, d'Imporzano M, et al. Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non- unions: a prospective randomised clinical study on 120 patients. Injury. 2008; 39(12):1391-1402.
16. Carreon LY, Glassman SD, Anekstein Y, Puno RM. Platelet gel (AGF) fails to increase fusion rates in instrumented posterolateral fusions.  Spine. 2005; 30(9):E243-E246.
17. Champagne BJ, O'Connor LM, Ferguson M, et al. Efficacy of anal fistula plug in closure of cryptoglandular fistulas: long-term follow-up. Dis Colon Rectum. 2006; 49(12):1817-1821.
18. Chang DW, Sanchez LA, Veith FJ, et al. Can a tissue-engineered skin graft improve healing of lower extremity foot wounds after revascularization? Ann Vasc Surg. 2000; 14(1):44-49.
19. Diaz JJ Jr, Guy J, Berkes MB, et al. Acellular dermal allograft for ventral hernia repair in the compromised surgical field. Am Surg. 2006; 72(12):1181-1187.
20. Eaglstein WH, Falanga V. Tissue engineering and the development of Apligraf^® a human skin equivalent. Adv Wound Care. 1998; 11(4Suppl):1-8.
21. Eaglstein WH, Falanga V. Tissue engineering for skin: an update. J Am Acad Dermatol. 1998; 39(6):1007-1010.
22. Edmonds M, Bates M, Doxford M, et al. New treatments in ulcer healing and wound infection. Diabetes Metab Res Rev. 2000; 16(Suppl 1):S51-S54. 
23. Edwards SG, Calandruccio JH. Autologous blood injections for refractory lateral epicondylitis. J Hand Surg Am. 2003; 28(2):272-278.  
24. Eisenberg M, Llewelyn D. Surgical management of hands in children with recessive dystrophic epidermolysis bullosa: use of allogeneic composite cultured skin grafts. Br J Plast Surg. 1998; 51(8):608-613.
25. Ellis CN. Bioprosthetic plugs for complex anal fistulas: an early experience. Curr Surg. 2007; 64(1):36-40.
26. Epstein E. Questions about study of cultured skin equivalent for venous ulcers. Arch Dermatol. 1998; 134(11): 1483-1484.
27. Epstein E. A controlled trial, LSE vs killed LSE, is needed. Arch Dermatol. 2000; 136(4):555-556.
28. Falabella AF, Valencia IC, Eaglstein WH, Schachner LA. Tissue-engineered skin (Apligraf^®) in the healing of patients with epidermolysis bullosa wounds. Arch Dermatol. 2000; 136(10):1225-1230.
29. Espinosa-de-los-Monteros A, de la Torre JI, Marrero I, et al. Utilization of human cadaveric acellular dermis for abdominal hernia reconstruction. Ann Plast Surg. 2007; 58(3):264-267.
30. 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 
31. Falanga V, Margolis D, Alvarez O, et al. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent.  Human Skin Equivalent Investigators Group. Arch Dermatol. 1998; 134(3):293-300.
32. Feldman DL, Rogers A, Karpinski RH. A prospective trial comparing Biobrane, Duoderm and xeroform for skin graft donor sites. Surg Gynecol Obstet. 1991; 173(1):1-5.
33. Feiz-Erfan I, Harrigan M, Sonntag VK, Harrington TR. Effect of autologous platelet gel on early and late graft fusion in anterior cervical spine surgery. J Neurosurg Spine. 2007; 7(5):496-502. 
34. Gamboa-Bobadilla GM. Implant breast reconstruction using acellular dermal matrix. Ann Plast Surg. 2006; 56(1):22-25. 
35. Gardner MJ, Demetrakopoulos D, Klepchick PR, Mooar PA. The efficacy of autologous platelet gel in pain control and blood loss in total knee arthroplasty. An analysis of the haemoglobin, narcotic requirement and range of motion. Int Orthop. 2007; 31(3):309-313.
36. Gerding RL, Emerman CL, Effron D, et al. Outpatient management of partial-thickness burns: Biobrane versus 1% silver sulfadiazine. Ann Emerg Med. 1990; 19(2):121-124.
37. Glasberg SB, D'Amico RA. Use of regenerative human acellular tissue (AlloDerm) to reconstruct the abdominal wall following pedicle TRAM flap breast reconstruction surgery. Plast Reconstr Surg. 2006; 118(1):8-15. 
38. Glover JL, Weingarten MS, Buchbinder DS, et al. A 4-year outcome-based retrospective study of wound healing and limb salvage in patients with chronic wounds. Adv Wound Care. 1997; 10(1):33-38.
39. Gohari S, Gambla C, Healey M, et al. Evaluation of tissue-engineered skin (human skin substitute) and secondary intention healing in the treatment of full thickness wounds after Mohs micrographic or excisional surgery. Dermatol Surg. 2002; 28(12):1107-1114.
40. Govindaraj S, Cohen M, Genden EM, et al. The use of acellular dermis in the prevention of Frey's syndrome. Laryngoscope. 2001; 111(11 Pt 1):1993-1998.
41. Guzman–Gardearzabal E, Leyva-Bohorquez G, Salas-Colin S, et al. Treatment of chronic ulcers in the lower extremities with topical becaplermin gel .01%: a multicenter open-label study. Adv Ther. 2000; 17(4):184-189.
42. He C, Hughes MA, Cherry GW, Arnold F. Effects of chronic wound fluid on the bioactivity of platelet-derived growth factor in serum-free medium and its direct effect on fibroblast growth. Wound Repair Regen. 1999; 7(2):97-105
43. Healy CM, Boorman JG. Comparison of E-Z Derm and Jelonet dressings for partial skin thickness burns. Burns Incl Therm Inj. 1989; 15(1):52-54.
44. Hee HT, Majd ME, Holt RT, Myers L. Do autologous growth factors enhance transforaminal lumbar interbody fusion? Eur Spine J. 2003; 12(4):400-407. 
45. Johnson EK, Gaw JU, Armstrong DN.  Efficacy of anal fistula plug vs. fibrin glue in closure of anorectal fistulas. Dis Colon Rectum. 2006; 49(3):371-376.
46. Karpenko AN, Dworkin JP, Meleca RJ, Stachler RJ. Cymetra injection for unilateral vocal fold paralysis. Ann Otol Rhinol Laryngol. 2003; 112(11):927-934.
47. Lal S, Barrow RE, Wolf SE, et al. Biobrane improves wound healing in burned children without increased risk of infection. Shock. 2000; 14(3):314-318.
48. Man D, Plosker H, Winland-Brown JE. The use of autologous platelet-rich plasma (platelet gel) and autologous platelet-poor plasma (fibrin glue) in cosmetic surgery. Plast Reconstr Surg. 2001; 107(1):229-237.
49. Margolis DJ, Kantor J, Santana J, et al. Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes Care. 2001; 24(3):483-488.
50. Mariconda M, Cozzolino F, Cozzolino A, et al. Platelet gel supplementation in long bone nonunions treated by external fixation. J Orthop Trauma. 2008; 22(5):342-345. 
51. Milstein CF, Akst LM, Hicks MD, et al. Long-term effects of micronized Alloderm injection for unilateral vocal fold paralysis. Laryngoscope. 2005; 115(9):1691-1696.
52. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med. 2006 ; 34(11):1774-1778.
53. Misra S, Raj PK, Tarr SM, Treat RC. Results of AlloDerm use in abdominal hernia repair. Hernia. 2008;12(3):247-250.
54. Morgan JE, Zraick RI, Griffin AW, et al. Injection versus medialization laryngoplasty for the treatment of unilateral vocal fold paralysis. Laryngoscope. 2007; 117(11):2068-2074.
55. Mostow EN, Haraway GD, Dalsing M, et al; OASIS Venus Ulcer Study Group. Effectiveness of an extracellular matrix graft (OASIS Wound Matrix) in the treatment of chronic leg ulcers: a randomized clinical trial. J Vasc Surg. 2005; 41(5):837-843.
56. Muhart M, McFalls S, Kirsner RS, et al. Behavior of tissue-engineered skin: a comparison of a living skin equivalent, autograft, and occlusive dressing in human donor sites. Arch Dermatol. 1999; 135(8):913-918.
57. Munster AM, Smith-Meek M, Shalom A. Acellular allograft dermal matrix: immediate or delayed epidermal coverage? Burns. 2001; 27(2):150-153.
58. Nahabedian MY. Secondary nipple reconstruction using local flaps and AlloDerm. Plast Reconstr Surg. 2005 ; 115(7):2056-2061.
59. Naughton G, Mansbridge J, Gentzkow G. A metabolically active human dermal replacement for the treatment of diabetic foot ulcers. Artif Organs. 1997; 21(11):1203-1210. 
60. Niezgoda JA, Van Gils CC, Frykberg RG, Hodde JP.  Randomized clinical trial comparing OASIS Wound Matrix to Regranex Gel for diabetic ulcers. Adv Skin Wound Care. 2005; 18(5 Pt 1):258-266.
61. O'Connor L, Champagne BJ, Ferguson MA, et al.  Efficacy of anal fistula plug in closure of Crohn's anorectal fistulas. Dis Colon Rectum. 2006; 49(10):1569-1573.
62. Oelschlager BK, Pellegrini,  CA, Hunete J, et al. Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: A multicenter, prospective, randomized trial. Ann Surg. 2006; 244(4):481-490.
63. Patton JH Jr, Berry S, Kralovich KA. Use of human acellular dermal matrix in complex and contaminated abdominal wall reconstructions. Am J Surg. 2007; 193(3):360-363.
64. Pham HT, Rosenblum BI, Lyons TE, et al. Evaluation of a human skin equivalent for the treatment of diabetic foot ulcers in a prospective, randomized, clinical trial. Wounds. 1999; 11(4):79-86.
65. Pollak RA, Edington H, Jensen JL, et al. A human dermal replacement for the treatment of diabetic foot ulcers. Wounds. 1997; 9(1):175-183.
66. Powell DM, Chang E, Farrior EH. Recovery from deep-plane rhytidectomy following unilateral wound treatment with autologous platelet gel: a pilot study. Arch Facial Plast Surg. 2001; 3(4):245-250.
67. Prasad JK, Feller I, Thomson PD. A prospective controlled trial of Biobrane versus scarlet red on skin graft donor areas. J Burn Care Rehabil. 1987; 8(5):384-386.
68. Preminger BA, McCarthy CM, Hu QY, et al. The influence of AlloDerm on expander dynamics and complications in the setting of immediate tissue expander/implant reconstruction: a matched-cohort study. Ann Plast Surg. 2008;60(5):510-513.
69. Purdue GF, Hunt JL, Still JM, et al. A multicenter clinical trial of biosynthetic skin replacement, Dermagraft-TC, compared with cryopreserved human cadaver skin for temporary coverage of excised burn wounds. J Burn Care Rehabil. 1997; 18(1 Pt 1):52-27.
70. Rees RS, Robson MC, Smiell JM, Perry BH. Becaplermin get in the treatment of pressure ulcers: a phase II randomized, double-blind placebo-controlled study. Wound Repair Regen. 1999; 7(3):141-147.
71. Salzberg CA.  Nonexpansive immediate breast reconstruction using human acellular tissue matrix graft (AlloDerm). Ann Plast Surg. 2006; 57(1):1-5.
72. Sams HH, Chen J, King LE. Graftskin treatment of difficult to heal diabetic foot ulcers: one center's experience. Dermatol Surg. 2002; 28(8):698-703.
73. Sclafani AP, Jacono AA, Dolitsky JN. Grafting of the peritonsillar fossa with an acellular dermal graft to reduce posttonsillectomy pain. Am J Otolaryngol. 2001; 22(6):409-414.
74. Sclafani AP, Romo T 3rd, Jacono AA, et al. Evaluation of acellular dermal graft in sheet (AlloDerm) and injectable (micronized AlloDerm) forms for soft tissue augmentation. Clinical observations and histological analysis. Arch Facial Plast Surg. 2000; 2(2):130-136.
75. Sinha UK, Saadat D, Doherty CM, Rice DH. Use of AlloDerm implant to prevent frey syndrome after parotidectomy. Arch Facial Plast Surg. 2003; 5(1):109-112.
76. Sinha UK, Shih C, Chang K, Rice DH. Use of AlloDerm for coverage of radial forearm free flap donor site. Laryngoscope. 2002; 112(2):230-234.
77. Spear SL, Parikh PM, Reisin E, Menon NG. Acellular dermis-assisted breast reconstruction. Aesthetic Plast Surg. 2008; 32(3):418-425.
78. Stephens E, Robinson JA, Gottlieb PA. Becaplermin and necrobiosis lipoidicum diabeticorum: results of a case control pilot study. J Diabetes Complications. 2001; 15(1):55-56.
79. Sullivan SA, Dailey RA. Graft contraction: a comparison of acellular dermis versus hard palate mucosa in lower eyelid surgery. Ophthal Plast Reconstr Surg. 2003; 19(1):14-24.
80. Tredget EE, Shankowsky HA, Groeneveld A, Burrell R. A matched-pair, randomized study evaluating the efficacy and safety of Acticoat silver-coated dressing for the treatment of burn wounds. J Burn Care Rehabil. 1998; 19(6):531-537.
81. Vanstraelen P. Comparison of calcium sodium alginate (KALTOSTAT) and porcine xenograft (E-Z DERM) in the healing of split-thickness skin graft donor sites. Burns. 1992; 18(2):145-148.
82. Waymack P, Duff RG, Sabolinski M. The effect of a tissue engineered bilayered living skin analog, over meshed split-thickness autografts on the healing of excised burn wounds. The Apligraf Burn Study Group. Burns. 2000; 26(7):609-619. 
83. Weiner BK, Walker M. Efficacy of autologous growth factors in lumbar intertransverse fusions. Spine. 2003; 28(17):1968-1970.
84. Yin HQ, Langford R, Burrell RE. Comparative evaluation of the antimicrobial activity of ACTICOAT antimicrobial barrier dressing. J Burn Care Rehabil. 1999; 20(3):195-200.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Bergin SM, Wraight P. Silver based wound dressings and topical agents for treating diabetic foot ulcers. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD005082
2. American Diabetes Association. Standards of Medical Care in Diabetes—2008. Diabetes Care. 2008; 31(Suppl 1):S12-S54. Available at: http://care.diabetesjournals.org/cgi/reprint/31/Supplement_1/S12. Accessed on July 14, 2009.
3. Centers for Medicare and Medicaid Services. National Coverage Determination for Blood-Derived Products for Chronic Non-Healing Wounds. NCD #270.3. Effective July 23, 2004. Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd. Accessed on July 14, 2009.
4. Centers for Medicare and Medicaid Services. National Coverage Determination for Porcine Skin and Gradient Pressure Dressings. NCD #270.5. Effective date not posted. Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd. Accessed on July 14, 2009.
5. Centers for Medicare and Medicaid Services. 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. Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd. Accessed on July 14, 2009.
6. Centers for Medicare and Medicaid Services. National Coverage Determination for Treatment of Decubitus Ulcers. NCD #270.4. Effective date not posted. Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd. Accessed on July 14, 2009.
7. Hayes Inc.   Hayes Medical Technology Directory. Skin Substitutes for Wound Healing. Winifred S Hayes, Inc., Lansdale PA. February 2004. Search updated February 21, 2008.
8. Hayes Inc.   Hayes Medical Technology Directory. Autologous Platelet Concentrate and Gel for Wound Healing. Winifred S Hayes, Inc., Lansdale PA. November 14, 2008.
9. Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD005486.

1. National Library of Medicine (NIH). Burns. Available at: http://www.nlm.nih.gov/medlineplus/burns.html. . Accessed on July 14, 2009.
2. National Library of Medicine (NIH). Diabetic Foot. Available at:  http://www.nlm.nih.gov/medlineplus/diabeticfoot.html. Accessed on July 14, 2009.

Acticoat
Actisorb^™
Alloderm^®
Apligraf^®
Autologel^™
Autologous Platelet Gel
Avaulta Plus^™
Becaplermin Gel (Trade Name Regranex^®)
Bilaminate Skin Substitute
Biobrane Bilayer Skin Substitute
Blood-Derived Growth Factors
Collamend
C-QUR^™
Cuffpatch^™
Culture-Derived Human Skin Equivalent
Cymetra^®
Dermagraft^®
DermaMatrix^®
Diabetic Ulcer
E-Z Derm^™
FlexHD^®
Frey's Syndrome
Gammagraft^™
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^®
Neodermis^™
Neoform Dermis^™
Oasis^™
OrCel^™
OrthADAPT^™
Pelvicol^®
Pelvisoft^®
PDGF
Platelet-Derived Growth Factors
Platelet-Derived Wound Healing Formula
Platelet Rich Plasma (PRP)
PriMatrix^™
Procuren^®
Recombinant Platelet-Derived Growth Factor
Regranex^®
SafeBlood^™
Silversorb^®
Strattice^™
Surgisis^®
TissueMend^®
Surgisis^® AFP^™
TransCyte^™
Unite^™
Vitagel^®
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.