Policy title: Products for Bio-Engineered Skin and Soft Tissue Substitutes

Policy number: MA 1.167

Effective date 7/1/2026

Policy

The following skin substitute products listed may be considered medically necessary when used for their FDA-cleared or clinically supported indications. All other skin substitute products are considered investigational as there is insufficient evidence to support a conclusion concerning the general health outcomes or benefits associated with this procedure.

Breast reconstructive surgery using allogeneic acellular dermal matrix products

Chronic, noninfected, full-thickness diabetic lower-extremity ulcers

Chronic, noninfected, partial- or full-thickness lower-extremity skin ulcers due to venous insufficiency

Dystrophic epidermolysis bullosa

Treatment of second- and third-degree burns

Policy Guidelines

A failed response is defined as an ulcer or skin deficit that has failed to respond to documented appropriate wound-care measures, has increased in size or depth, or has not changed in baseline size or depth and has no indication that improvement is likely (such as granulation, epithelialization or progress towards closing).

Wound healing is impaired by the systemic use of tobacco. Therefore, ideally patients who have smoked will have ceased smoking or have refrained from systemic tobacco intake for at least 4 weeks during conservative wound care and prior to planned bioengineered skin replacement therapy.

This medical policy applies to Medicare Advantage plans offered by Capital Blue Cross and its subsidiaries.

Cross-references:
MA 1.158 Application of bio-engineered skin and soft tissue substitutes
MA 1.159 Amniotic membrane and amniotic fluid
MA 4.028 Wound and burn care and specialized treatment centers

Description/Background

Skin and Soft Tissue Substitutes

Bioengineered skin and soft tissue substitutes may be either acellular or cellular. Acellular products (e.g., dermis with cellular material removed) contain a matrix or scaffold composed of materials such as collagen, hyaluronic acid, and fibronectin. Acellular dermal matrix (ADM) products can differ in a number of ways, including as species source (human, bovine, porcine), tissue source (e.g., dermis, pericardium, intestinal mucosa), additives (e.g., antibiotics, surfactants), hydration (wet, freeze-dried), and required preparation (multiple rinses, rehydration).

Cellular products contain living cells such as fibroblasts and keratinocytes within a matrix. The cells contained within the matrix may be autologous, allogeneic, or derived from other species (e.g., bovine, porcine). Skin substitutes may also be composed of dermal cells, epidermal cells, or a combination of dermal and epidermal cells, and may provide growth factors to stimulate healing. Bioengineered skin substitutes can be used as either temporary or permanent wound coverings.

Applications

There are a large number of potential applications for artificial skin and soft tissue products. One large category is nonhealing wounds, which potentially encompasses diabetic neuropathic ulcers, vascular insufficiency ulcers, and pressure ulcers. A substantial minority of such wounds do not heal adequately with standard wound care, leading to prolonged morbidity and increased risk of mortality. For example, nonhealing lower-extremity wounds represent an ongoing risk for infection, sepsis, limb amputation, and death. Bioengineered skin and soft tissue substitutes have the potential to improve rates of healing and reduce secondary complications.

Other situations in which bioengineered skin products might substitute for living skin grafts include certain postsurgical states (e.g., breast reconstruction) in which skin coverage is inadequate for the procedure performed, or for surgical wounds in patients with compromised ability to heal. Second- and third-degree burns are another indication in which artificial skin products may substitute for auto- or allografts. Certain primary dermatologic conditions that involve large areas of skin breakdown (e.g., bullous diseases) may also be conditions in which artificial skin products can be considered as substitutes for skin grafts. ADM products are also being evaluated in the repair of other soft tissues including rotator cuff repair, following oral and facial surgery, hernias, and other conditions.

Regulatory Status

The U.S. Food and Drug Administration (FDA) does not refer to any product or class of products as “skin substitutes.” However, products commonly described as “skin substitutes” are regulated by FDA under one of four categories described below depending on the origin and composition of the product.

Human Cells, Tissues, and Cellular and Tissue-Based Products – Cells and tissues taken from human donors and transplanted to a recipient are regulated under PHS 361 [21 CFR 1270 & 1271]. This regulation describes the rules concerning the use of HCT/Ps for human medical purposes. The final rule, 21 CFR Part 1271, became effective on April 4, 2001. HCT/Ps are regulated by the Center for Biologics Evaluation and Research (CBER), which oversees biological and related products including blood, vaccines, allergens, tissues, and cellular and gene therapies. Establishments producing HCT/Ps must register with FDA and list their HCT/Ps. HCT/P establishments are not required to demonstrate safety or effectiveness, and FDA does not evaluate safety or effectiveness of these products.

Premarket Approval – Premarket approval (PMA) is the FDA’s required process of scientific review to ensure the safety and effectiveness of Class III devices. Before Class III devices can be marketed, they must have an approved PMA application. Products regulated under PMA require evidence demonstrating they promote wound healing.

510(k) Submissions – A 510(k) submission is a premarket submission to demonstrate that a device is substantially equivalent to a legally marketed device [21 CFR 807.92(a)(3)]. Submitters must compare their device to one or more similar devices. Unlike PMA, 510(k) clearance does not typically require clinical evidence demonstrating effectiveness in wound healing.

Humanitarian Device Exemption (HDE) – An HDE is similar to a PMA but is exempt from effectiveness requirements. The applicant must demonstrate that no comparable devices are available and that the device addresses a condition affecting fewer than 4,000 patients per year in the United States. Approval is based on probable benefit rather than demonstrated effectiveness.

Human Amniotic Membrane (HAM)

HAM consists of two conjoined layers, the amnion and chorion, and forms the innermost lining of the amniotic sac or placenta. When prepared for use as an allograft, the membrane is harvested immediately after birth, cleaned, sterilized, and either cryopreserved or dehydrated. Products derived from amnion, chorion, amniotic fluid, and umbilical cord are being studied for the treatment of a variety of conditions including chronic diabetic ulcers, venous ulcers, knee osteoarthritis, plantar fasciitis, and ophthalmic conditions. These products may be applied as patches, suspensions, particulates, or connective tissue extractions.

Fresh amniotic membrane contains collagen, fibronectin, hyaluronic acid, and growth factors, along with cytokines and anti-inflammatory proteins. Evidence suggests anti-inflammatory, anti-fibroblastic, and antimicrobial properties. HAM is considered nonimmunogenic and has not been observed to cause a substantial immune response. These properties may be retained in processed HAM products, providing regenerative potential.

Use of HAM grafts fixed by sutures is an established treatment for corneal surface disorders including neurotrophic keratitis, corneal ulcers and melts, and persistent epithelial defects. Amniotic membrane products are also being evaluated for broader applications including skin wounds, burns, leg ulcers, and prevention of tissue adhesion.

Amniotic Fluid

Amniotic fluid surrounds the fetus during pregnancy and provides protection and nourishment. It contains proteins, carbohydrates, peptides, fats, amino acids, enzymes, hormones, pigments, and fetal cells. Amniotic fluid has been compared with synovial fluid and is being evaluated for orthopedic conditions such as osteoarthritis and plantar fasciitis.

Amniotic membrane and amniotic fluid are also being investigated as sources of pluripotent stem cells, which can differentiate into multiple cell types. Use of stem cells in orthopedic applications is addressed in evidence review MP 2.080.

Regulatory Status

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation, Title 21, parts 1270 and 1271. In 2017, the FDA published clarification of what is considered minimal manipulation and homologous use for human cells, tissues, and cellular and tissue-based products (HCT/Ps).

HCT/Ps are defined as human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. If an HCT/P does not meet the criteria below and does not qualify for any of the stated exceptions, the HCT/P will be regulated as a drug, device, and/or biological product, and applicable regulations and premarket review will be required.

Autologous skin grafts, also referred to as autografts, are permanent covers that use skin from different parts of the individual’s body. These grafts consist of the epidermis and a dermal component of variable thickness. A split-thickness skin graft (STSG) includes the entire epidermis and a portion of the dermis. A full thickness skin graft (FTSG) includes all layers of the skin. Although autografts are the optimal choice for full thickness wound coverage, areas for skin harvesting may be limited, particularly in cases of large burns or venous stasis ulceration. Harvesting procedures are painful, disfiguring and require additional wound care.

Allografts, which use skin from another human (e.g., cadaver), and xenografts, which use skin from another species (e.g., porcine or bovine), may also be employed as temporary skin replacements, but they must later be replaced by an autograft or the ingrowth of the patient’s own skin.

Bioengineered skin / cultured epidermal autografts (CEA) are autografts derived from the patient’s own skin cells grown or cultured from very small amounts of skin or hair follicle. Production time is prolonged. One such product is grown on a layer of irradiated mouse cells, bestowing some elements of a xenograft. Widespread usage has not been available due to limited availability or access to the technology.

Bioengineered Skin Substitutes or Cellular and Tissue-Based Products (CTPs), referred to as skin substitutes by CMS, the current procedural terminology (CPT) and the healthcare common procedure coding manuals, have been developed in an attempt to circumvent problems inherent with autografts, allografts and xenografts. These constitute biologic covers for refractory wounds with full thickness skin loss secondary to 3rd degree burns or other disease processes such as diabetic neuropathic ulcers and the skin loss of chronic venous stasis or venous hypertension. The production of these biologic skin substitutes or CTPs generally involves the creation of immunologically inert biological products containing protein, hormones or enzymes seeded into a matrix which may provide protein or growth factors proposed to stimulate or facilitate healing or promote epithelialization. A variety of biosynthetic and tissue-engineered skin substitution products marketed as human skin equivalents (HSE) or cellular or tissue-based products (CTP) are manufactured under an array of trade names and marketed for a variety of indications. All are procured, produced, manufactured, processed and promoted in sufficiently different manners to preclude direct product comparison for equivalency or superiority in randomized controlled trials. Sufficient data is available to establish distinct inferiority to human skin autografts and preclude their designation as skin equivalence.

Bioengineered skin substitutes or CTPs are classified into the following types:

• Human skin allografts derived from donated human skin (cadavers)
• Allogeneic matrices derived from human tissue (fibroblasts or membrane)
• Composite matrices derived from human keratinocytes, fibroblasts and xenogeneic collagen
• Acellular matrices derived from xenogeneic collagen or tissue

Human skin allografts are bioengineered from human skin components and human tissue which have had intact cells removed or treated to avoid immunologic rejection. They are available in different forms promoted to allow scaffolding, soft tissue filling, growth factors and other bioavailable hormonal or enzymatic activity.

Allogeneic matrices are usually derived from human neonatal fibroblasts of the foreskin that may contain metabolically active or regenerative components primarily used for soft tissue support, though some have been approved for the treatment of full-thickness skin and soft tissue loss. Most are biodegradable and disappear after 3-4 weeks implantation.

Composite matrices are derived from human keratinocytes and fibroblasts supported by a scaffold of synthetic mesh or xenogeneic collagen. These are also referred to as human skin equivalents but are unable to be used as autografts due to immunologic rejection or degradation of the living components by the host. Active cellular components continue to generate bioactive compounds and protein that may accelerate wound healing and epithelial regrowth.

Acellular matrices are derived from other than human skin and include the majority of bioengineered skin substitutes. All are composed of allogeneic or xenogeneic-derived collagen, membrane, or cellular remnants proposed to stimulate or exaggerate the characteristics of human skin. All propose to promote healing by the creation of localized intensification of an array of hormonal and enzymatic activity to accelerate closure by migration of native dermal and epithelial components, rather than function as distinctly incorporated tissue closing the skin defect.

Rationale

Summary of evidence

Breast Reconstruction

For individuals who are undergoing breast reconstruction who receive allogeneic acellular dermal matrix (ADM) products, the evidence includes randomized controlled trials (RCTs) and systematic reviews. Relevant outcomes are symptoms, morbid events, functional outcomes (including quality of life [QOL]), and treatment-related morbidity. A systematic review found no difference in overall complication rates with ADM allograft compared with standard procedures for breast reconstruction. Reconstructions with ADM have been reported to have higher seroma, infection, and necrosis rates than reconstructions without ADM. However, capsular contracture and malposition of implants may be reduced. Thus, in cases where there is limited tissue coverage, the available evidence may inform patient decision making about reconstruction options. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Tendon Repair

For individuals who are undergoing tendon repair who receive GraftJacket, the evidence includes an RCT. Relevant outcomes are symptoms, morbid events, functional outcomes, QOL, and treatment-related morbidity. The RCT identified found improved outcomes with the GraftJacket ADM allograft for rotator cuff repair. Although these results were positive, additional studies with a larger number of patients is needed to evaluate the consistency of the effect. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Surgical Repair of Hernias or Parastomal Reinforcement

For individuals who are undergoing surgical repair of hernias or parastomal reinforcement who receive acellular collagen-based scaffolds, the evidence includes RCTs. Relevant outcomes are symptoms, morbid events, functional outcomes, QOL, and treatment-related morbidity. Several comparative studies including RCTs have shown no difference in outcomes between tissue-engineered skin substitutes and either standard synthetic mesh or no reinforcement. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Diabetic Lower-Extremity Ulcers

For individuals who have diabetic lower-extremity ulcers who receive AlloPatch, Apligraf, Dermagraft, Integra, mVASC, or TheraSkin, the evidence includes RCTs. Relevant outcomes are symptoms, change in disease status, morbid events, and QOL. Randomized controlled trials reporting complete wound healing outcomes with at least 12 weeks of follow-up have demonstrated the efficacy of AlloPatch (reticular ADM), Apligraf and Dermagraft (living cell therapy), Integra (biosynthetic), mVASC, and TheraSkin over the standard of care (SOC). The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have diabetic lower-extremity ulcers who receive ADM products other than AlloPatch, Apligraf, Dermagraft, Integra, mVASC, or TheraSkin, the evidence includes RCTs. Relevant outcomes are symptoms, change in disease status, morbid events, and QOL. Results from a multicenter RCT showed some benefit of DermACELL that was primarily for the subgroup of patients who only required a single application of the ADM. Studies are needed to further define those populations who might benefit from this treatment. Additional study with a larger number of subjects is needed to evaluate the effect of GraftJacket, DermACELL, Cytal, PriMatrix, and Oasis Wound Matrix, compared with current SOC or other advanced wound therapies. An RCT of Omega3 Wound (Kerecis) has been published and 2 larger RCTs are registered and reported as completed but have not been published. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Lower-Extremity Ulcers due to Venous Insufficiency

For individuals who have lower-extremity ulcers due to venous insufficiency who receive Apligraf or Oasis Wound Matrix, the evidence includes RCTs. Relevant outcomes are symptoms, change in disease status, morbid events, and QOL. Randomized controlled trials have demonstrated the efficacy of Apligraf living cell therapy and xenogeneic Oasis Wound Matrix over the SOC. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have lower-extremity ulcers due to venous insufficiency who receive bioengineered skin substitutes other than Apligraf or Oasis Wound Matrix, the evidence includes RCTs. Relevant outcomes are disease-specific survival, symptoms, change in disease status, morbid events, and QOL. In a moderately large RCT, Dermagraft was not shown to be any more effective than controls for the primary or secondary endpoints in the entire population and was only slightly more effective than controls (an 8% to 15% increase in healing) in subgroups of patients with ulcer durations of 12 months or less or size of 10 cm or less. Additional studies with a larger number of subjects is needed to evaluate the effect of the xenogeneic PriMatrix skin substitute versus the current SOC. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Deep Dermal Burns

For individuals who have deep dermal burns who receive bioengineered skin substitutes (i.e., Epicel, Integra Dermal Regeneration Template), the evidence includes RCTs. Relevant outcomes are symptoms, change in disease status, morbid events, functional outcomes, QOL, and treatment-related morbidity. Overall, few skin substitutes have been approved, and the evidence is limited for each product. Epicel (living cell therapy) has received U.S. Food and Drug Administration approval under a humanitarian device exemption for treatment of deep dermal or full-thickness burns comprising a total body surface area of 30% or more. Comparative studies have demonstrated improved outcomes for biosynthetic skin substitute Integra Dermal Regeneration Template for treatment of burns. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have deep dermal burns who are treated with the ReCell autologous cell harvesting device, the evidence includes RCTs. One RCT evaluated ReCell as an adjunct to meshed autologous skin grafting and another compared ReCell head-to-head with skin grafting. Although the ReCell device was comparable to standard care on outcomes such as complete wound closure, confidence in the strength of the overall body of evidence is limited by individual study limitations and heterogeneity of populations, interventions, and outcome measure across studies. Additional RCT evidence in the intended use population is needed. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Dystrophic Epidermolysis Bullosa

For individuals who have dystrophic epidermolysis bullosa who receive OrCel, the evidence includes a case series. Relevant outcomes are symptoms, change in disease status, morbid events, and QOL. OrCel was approved under a humanitarian drug exemption for use in patients with dystrophic epidermolysis bullosa undergoing hand reconstruction surgery, to close and heal wounds created by the surgery, including those at donor sites. Outcomes have been reported in a small series (e.g., 5 patients). The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Definitions

Autologous skin grafts, also referred to as autografts, are permanent covers that use skin from different parts of the individual’s body. These grafts consist of the epidermis and a dermal component of variable thickness. A split-thickness skin graft (STSG) includes the entire epidermis and a portion of the dermis. A full thickness skin graft (FTSG) includes all layers of the skin. Although autografts are the optimal choice for full thickness wound coverage, areas for skin harvesting may be limited, particularly in cases of large burns or venous stasis ulceration. Harvesting procedures are painful, disfiguring and require additional wound care.

Allografts, which use skin from another human (e.g., cadaver), and xenografts, which use skin from another species (e.g., porcine or bovine), may also be employed as temporary skin replacements, but they must later be replaced by an autograft or the ingrowth of the patient’s own skin.

Bioengineered skin / cultured epidermal autografts (CEA) are autografts derived from the patient’s own skin cells grown or cultured from very small amounts of skin or hair follicle. Production time is prolonged. One such product is grown on a layer of irradiated mouse cells, bestowing some elements of a xenograft. Widespread usage has not been available due to limited availability or access to the technology.

Bioengineered Skin Substitutes or Cellular and Tissue-Based Products (CTPs), referred to as skin substitutes by CMS, the current procedural terminology (CPT) and the healthcare common procedure coding manuals, have been developed in an attempt to circumvent problems inherent with autografts, allografts and xenografts. These constitute biologic covers for refractory wounds with full thickness skin loss secondary to 3rd degree burns or other disease processes such as diabetic neuropathic ulcers and the skin loss of chronic venous stasis or venous hypertension. The production of these biologic skin substitutes or CTPs generally involves the creation of immunologically inert biological products containing protein, hormones or enzymes seeded into a matrix which may provide protein or growth factors proposed to stimulate or facilitate healing or promote epithelialization. A variety of biosynthetic and tissue-engineered skin substitution products marketed as human skin equivalents (HSE) or cellular or tissue-based products (CTP) are manufactured under an array of trade names and marketed for a variety of indications. All are procured, produced, manufactured, processed and promoted in sufficiently different manners to preclude direct product comparison for equivalency or superiority in randomized controlled trials. Sufficient data is available to establish distinct inferiority to human skin autografts and preclude their designation as skin equivalence.

Bioengineered skin substitutes or CTPs are classified into the following types:

• Human skin allografts derived from donated human skin (cadavers)
• Allogeneic matrices derived from human tissue (fibroblasts or membrane)
• Composite matrices derived from human keratinocytes, fibroblasts and xenogeneic collagen
• Acellular matrices derived from xenogeneic collagen or tissue

Human skin allografts are bioengineered from human skin components and human tissue which have had intact cells removed or treated to avoid immunologic rejection. They are available in different forms promoted to allow scaffolding, soft tissue filling, growth factors and other bioavailable hormonal or enzymatic activity.

Allogeneic matrices are usually derived from human neonatal fibroblasts of the foreskin that may contain metabolically active or regenerative components primarily used for soft tissue support, though some have been approved for the treatment of full-thickness skin and soft tissue loss. Most are biodegradable and disappear after 3-4 weeks implantation.

Composite matrices are derived from human keratinocytes and fibroblasts supported by a scaffold of synthetic mesh or xenogeneic collagen. These are also referred to as human skin equivalents but are unable to be used as autografts due to immunologic rejection or degradation of the living components by the host. Active cellular components continue to generate bioactive compounds and protein that may accelerate wound healing and epithelial regrowth.

Acellular matrices are derived from other than human skin and include the majority of bioengineered skin substitutes. All are composed of allogeneic or xenogeneic-derived collagen, membrane, or cellular remnants proposed to stimulate or exaggerate the characteristics of human skin. All propose to promote healing by the creation of localized intensification of an array of hormonal and enzymatic activity to accelerate closure by migration of native dermal and epithelial components, rather than function as distinctly incorporated tissue closing the skin defect.

Disclaimer

Capital Blue Cross’ medical policies are used to determine coverage for specific medical technologies, procedures, equipment, and services. These medical policies do not constitute medical advice and are subject to change as permitted by law or applicable clinical evidence from independent treatment guidelines. Treating providers are solely responsible for medical advice and treatment of members. These policies are not a guarantee of coverage or payment. Payment of claims is subject to a determination regarding the member’s benefit program and eligibility on the date of service, and a determination that the services are medically necessary and appropriate. Final processing of a claim is based upon the terms of contract that applies to the members’ benefit program, including benefit limitations and exclusions. If a provider or a member has a question concerning this medical policy, please contact Capital Blue Cross’ Provider Services or Member Services.

Coding Information

Note: This list of codes is not exhaustive and may change from time to time as permitted by law or applicable clinical guidelines. The inclusion of a code in this section is not a guarantee of coverage or payment. In addition, not all covered services are eligible for separate reimbursement.

Covered when medically necessary, associated procedures:

Covered when medically necessary for breast reconstructive surgery using allogeneic acellular dermal matrix products:

Covered when medically necessary for treatment of chronic, noninfected, full-thickness diabetic lower-extremity ulcers:

Covered when medically necessary for treatment of chronic, noninfected, partial- or full-thickness lower-extremity skin ulcers due to venous insufficiency:

Covered when medically necessary for treatment of dystrophic epidermolysis bullosa:

Covered when medically necessary for treatment of second- and third-degree burns:

Investigational; therefore not covered:

References

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2. U.S. Food and Drug Administration. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use. December 2017. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/regulatory-considerations-human-cells-tissues-and-cellular-and-tissue-based-products-minimal. Accessed March 23, 2025.
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23. Fleshman JW, Beck DE, Hyman N, et al. A prospective, multicenter, randomized, controlled study of non-cross-linked porcine acellular dermal matrix fascial sublay for parastomal reinforcement in patients undergoing surgery for permanent abdominal wall ostomies. Dis Colon Rectum. May 2014;57(5):623-631. PMID 24819103
24. Kalaiselvan R, Carlson GL, Hayes S, et al. Recurrent intestinal fistulation after porcine acellular dermal matrix reinforcement in enteric fistula takedown and simultaneous abdominal wall reconstruction. Hernia. Jun 2020;24(3):537-543. PMID 31811593
25. Santema TB, Poyck PP, Ubbink DT. Skin grafting and tissue replacement for treating foot ulcers in people with diabetes. Cochrane Database Syst Rev. Feb 11 2016;2:CD011255. PMID 26866804
26. Veves A, Falanga V, Armstrong DG, et al. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care. Feb 2001;24(2):290-295. PMID 11213881
27. Marston WA, Hanft J, Norwood P, et al. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care. Jun 2003;26(6):1701-1705. PMID 12766097
28. Frykberg RG, Marston WA, Cardinal M. The incidence of lower-extremity amputation and bone resection in diabetic foot ulcer patients treated with a human fibroblast-derived dermal substitute. Adv Skin Wound Care. Apr 2015;28(4):17-20. PMID 25407083
29. Zelen CM, Orgill DP, Serena TE, et al. A prospective, randomized, controlled, multicentre clinical trial examining healing rates, safety and cost to closure of an acellular reticular allograft human dermis versus standard of care in the treatment of chronic diabetic foot ulcers. Int Wound J. Apr 2017;14(2):307-315. PMID 27073000
30. Zelen CM, Orgill DP, Serena TE, et al. An aseptically processed, acellular, reticular, allogeneic human dermis improves healing in diabetic foot ulcers: a prospective, randomized, controlled, multicenter follow-up trial. Int Wound J. Oct 2018;15(5):731-739. PMID 29682897
31. Driver VR, Lavery LA, Reyzelman AM, et al. A clinical trial of Integra Template for the closure of diabetic foot ulcers. Wound Repair Regen. May 2015;23(6):891-900. PMID 26297933
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Policy History

• MP 1.167
  • 03/09/2026 New Policy Creation.

Plans issued by Capital Blue Cross and it’s subsidiaries are independent licensees of the Blue Cross Blue Shield Association. Communications issued by Capital Blue Cross in its capacity as administrator of programs and provider relations for all companies.

Health care benefit programs issued or administered by Capital Blue Cross and/or its subsidiaries, Capital Advantage Insurance Company^®, Capital Advantage Assurance Company^® and Keystone Health Plan^® Central. Independent licensees of the Blue Cross BlueShield Association. Communications issued by Capital Blue Cross in its capacity as administrator of programs and provider relations for all companies.