*** This policy was implemented in the absence of National Coverage Determinations (NCD) or Local Coverage Determinations (LCD) coverage criteria. This policy applies to all Blue Medicare HMO, Blue Medicare PPO, Healthy Blue + Medicare^SM (HMO-POS D-SNP), Blue Medicare Rx members, and members of any third-party Medicare plans supported by Blue Cross NC through administrative or operational services. ***

Description of Procedure or Service

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 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. Tissue-engineered skin substitutes can be used as either temporary or permanent wound coverings.

There are many potential applications for artificial skin and soft tissue products. One large category is nonhealing wounds, which potentially includes diabetic neuropathic foot ulcers, vascular insufficiency ulcers (also known as venous statis ulcer), 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.

Many products available using placental, amnion and chorion (specifically Human amniotic membrane (HAM)), amniotic fluid, and umbilical cord components are being studied for the treatment of a variety of conditions, including chronic full-thickness diabetic lower-extremity ulcers, venous ulcers, knee osteoarthritis, plantar fasciitis, and ophthalmic conditions. The products are formulated either as patches, which can be applied as wound covers, or as suspensions or particulates, or connective tissue extractions, which can be injected or applied topically.

Policy Statement

Coverage will be provided for Bioengineered Skin and Soft Tissue Substitute for Diabetic Foot Ulcers, Venous Stasis Ulcer and Chronic Wounds when it is determined to be medically necessary when the medical criteria and guidelines shown below are met.

Benefit Application

Please refer to the member’s individual Evidence of Coverage (EOC) for benefit determination.  Coverage will be approved according to the EOC limitations if the criteria are met.

Coverage decisions will be made in accordance with:

• The Centers for Medicare & Medicaid Services (CMS) national coverage decisions;
• General coverage guidelines included in original Medicare manuals unless superseded by operational policy letters or regulations; and
• Written coverage decisions of local Medicare carriers and intermediaries with jurisdiction for claims in the geographic area in which services are covered.

Benefit payments are subject to contractual obligations of the Plan.  If there is a conflict between the general policy guidelines contained in the Medical Coverage Policy Manual and the terms of the member’s particular Evidence of Coverage (EOC), the EOC always governs the determination of benefits.

Definitions

• Acellular - tissue-engineered graft that acts as a scaffold for wound healing by removing all cellular components from natural tissues (like human or animal skin) and leaving behind the collagen-rich extracellular matrix
• Allogenic - type of skin graft taken from a genetically non-identical donor of the same species (human) and used to cover wounds
• Antigenic - material designed to replace damaged skin that contains antigens, which are substances capable of triggering an immune response in the recipient
• Autografts/tissue cultured autografts - Include the harvest or application of an autologous skin graft. These products are designed to circumvent the challenges with autologous skin grafts in the treatment of chronic wounds, ulcers, or burns.
• Autologous - regenerative skin product or graft derived from a patient's own cells and tissues, designed to replace, or promote the healing of damaged skin
• Axonal Degeneration - the process of structural breakdown of an axon, the long projection of a neuron that transmits signals, which can occur due to injury, aging, or disease, leading to neuronal dysfunction and loss of neurological function
• Cellular - relating to or consisting of living cells
• Chronic Wound - A chronic wound may be defined as a wound physiologically impaired due toa disruption of the wound’s healing cycle resulting from impaired angiogenesis, innervation, cellular migration, or other deficits for 4 weeks or longer.
• Demyelination - the loss or damage of the myelin sheath, a protective fatty layer that insulates and protects nerve fibers (axons) in the central (brain and spinal cord) and peripheral (outside the brain and spinal cord) nervous systems
• Elute - the controlled release of a therapeutic substance, such as an antibiotic or antiseptic, from a wound dressing or other device directly into the wound
• Failed response - Increased size or depth, no change in baseline size or depth, or no sign of improvement or indication that improvement is likely (such as granulation, epithelialization, or progress towards closing.
• Healed ulcer (completed healing) - 100 percent re-epithelialization without drainage or dressing noted on 2 occasions at least 2 weeks apart.
• Immunogenicity - the ability of a material, like a wound dressing or implanted scaffold, to trigger an immune response from the body
• In vitro - an "in vitro" experiment or model occurs in a lab setting, outside of a living organism, rather than in a real wound or body
• In Vivo - experiment, study, or treatment that takes place within a whole, living organism, such as a human or animal, rather than in a lab dish (in vitro)
• Mesenchymal stem cells - type of adult stem cell found in various tissues throughout the body (MSCs can differentiate into multiple cell types, including bone, cartilage, fat, muscle, and connective tissue cells)
• Neurotropic - the role of nerve cells and nerve-related factors in the healing process
• Nonimmunogenic - a substance, molecule, or cell that fails to trigger an immune response from the body's immune system
• Scaffolding - A support, delivery vehicle, or matrix for facilitating the migration, binding, or transport of cells or bioactive molecules used to replace, repair, or regenerate tissues.
• Stalled Wound - An ulcer that has entered a nonhealing or intransigent phase.
• Standard of Care (SOC) - Refers to a Best Practice recommendation and it is not to be interpreted as the legal definition of Standard of care for either Diabetic Foot Ulcer (DFU); Vascular Insufficiency Ulcer (VIU) and/or Chronic Pressure Non-Healing Wound.
• Wound dressing or coverings - Applications applied to wounds as a selective barrier to maintain a clean wound environment, cover and protect wounds from the surrounding environment to promote optimal environment for wound healing.

Indications for Coverage

The use of skin and tissue substitutes have been scientifically validated and therefore may be medically necessary when criteria met for the following indications:

1. Diabetic Neuropathic Foot Ulcers
2. Vascular Insufficiency Ulcer
3. Chronic Pressure Non-Healing Wounds

There is insufficient evidence to support the efficacy of bioengineered Skin and Tissue Substitute to improve on health outcomes for all other indications and is therefore all other use not listed above is considered investigational and therefore not reasonable and necessary.

All use of skin and soft tissue substitutes may be subjected to the Plan Medical Director Review.

Clinical Inclusion Criteria

Use of skin and tissue substitute may be considered medically necessary when ALL the following are met:

1. The skin substitute product must satisfy at least ONE of the following: 
   • AATB (American Association of Tissue Banks) Approval: The skin substitute product must meet all applicable regulation and standards established by the American Association of Tissue Banks for procuring and processing human cells, tissues, and cellular or tissue-based products (HCT/Ps), or
   • FDA Approval: The skin substitute product must meet all product specific FDA requirements.
2. And ALL the following are met: 
   • Documentation noting the member is a non-smoker, or has completed or is currently in smoking cessation therapy; and 
   • Wound characteristics and treatment plan are documented including ALL the following: 
     • Partial- or full-thickness skin defect, clean, and free of necrotic debris, exudate, or infection and 
     • Tissue approximation would cause excessive tension or functional loss; and 
     • No involvement of tendon, muscle, joint capsule, or exposed bone or sinus tracts; and 
     • No wound infection 
3. And the skin substitute product must be used in ONE of the following specific indications:
   
   Diabetic Neuropathic Foot Ulcers (DFU) - Skin and tissue substitutes are considered medically necessary for the treatment of diabetic neuropathic foot ulcers when all the criteria are met:
   1. Physician documentation of medical management for clinically documented type 1 or type 2 diabetes
   2. Failure to achieve at least 50% ulcer area reduction with a minimum of 4 weeks of documented compliance with standard of care (SOC) treatment which includes but not limited to mechanical offloading, infection control, limb elevation, debridement of necrotic tissue, management of systemic disease and medications, nutrition assessment, tissue perfusion and oxygenation, education regarding care of the foot, including callus nails, and fitting of shoes, as well as counseling on the risk of continued tobacco use. In addition, maintenance of a moist ulcer environment through appropriate dressings facilitates development of healthy granulation tissue and epithelialization and potentiates complete healing at an ulcer site.
   3. The wound is a non-infected full thickness neuropathic diabetic foot ulcer and at least 1.0cm2 in size due to clinically documented diabetic neuropathy.
   4. The ulcer extends through the dermis but does not involve the tendon, muscle, capsule, or exposure to bone.
   5. There is adequate arterial blood supply to support tissue growth.
   6. The extremity is free of Charcot’s arthropathy.
      
      The following products may be considered medically necessary for treatment of chronic, noninfected, full-thickness, lower extremity diabetic ulcers when the above criteria are met:
   • AFFINITY (Q4159)
   • ALLOPATCH HD^®, OR FLEX HD (Q4128)
   • AMNIOBAND^® MEMBRANE OR GUARDIAN (Q4151)
   • APLIGRAF^® (Q4101)
   • DERMACELL^® (Q4122)
   • DERMA-GIDE^® (Q4203)
   • DERMAGRAFT^® (now known TranCyte) (Q4182) (Q4106)
   • EPICORD^® (Q4187)
   • EPIFIX^® (Q4186)
   • GRAFIX PRIME, GRAFIX PL PRIME, STRAVIX AND STRAVIXPL (Q4133)
   • GRAFTJACKET^® (Q4107)
   • INTEGRA^® DRT/ INTEGRA^® OMNIGRAFT^™ DRM (Q4105)
   • KERECIS^® OMEGA3 (A2019)
   • KERECIS^® OMEGA3 MARIGEN (Q4158)
   • NUSHIELD^® (Q4160)
   • OASIS^® WOUND MATRIX (Q4102)
   • PRIMATRIX^® (Q4110)
   • THERASKIN^® (Q4121)
     
     Note: All other skin or soft tissue substitutes products for diabetic lower extremity ulcers not included above are considered experimental, investigational, and unproven due to insufficient evidence in the peer reviewed medical literature to support their clinical effectiveness and validity of successful health outcome and are therefore not medically necessary.
     
     Chronic Venous Insufficiency Lower Extremity Ulcer (VLU) - Skin and tissue substitutes are considered medically necessary for the treatment of chronic venous insufficiency ulcers when all the criteria are met:
   1. Physician documentation of medical management for clinically documented chronic lower extremity venous insufficiency.
   2. Failure to achieve at least 50% ulcer area reduction with a minimum of 4 weeks of documented compliance with standard of care (SOC) treatment which includes but not limited to infection control, mechanical compression, limb elevation, debridement of necrotic tissue, management of systemic disease and medications, nutrition assessment, tissue perfusion and oxygenation, education regarding care of the foot, including callus nails, and fitting of shoes, as well as counseling on the risk of continued tobacco use.
   3. In addition, maintenance of a moist ulcer environment through appropriate dressings facilitates development of healthy granulation tissue and epithelialization and potentiates complete healing at an ulcer site.
   4. The wound is a non-infected full thickness venous stasis ulcer and at least 1.0cm2 in size due to clinically documented venous insufficiency.
   5. The ulcer extends through the dermis but does not involve the tendon, muscle, capsule, or exposure to bone.
   6. There is adequate arterial blood supply to support tissue growth.
      
      The following products may be considered medically necessary for treatment of chronic, noninfected, full-thickness, lower extremity venous insufficiency ulcers when the above criteria are met:
   • AMNIOBAND^® MEMBRANE OR GUARDIAN (Q4151)
   • APLIGRAF^® (Q4101)
   • DERMAGRAFT^® (Q4182)
   • EPIFIX^® (Q4186)
   • OASIS^® WOUND MATRIX (Q4102)
     
     Note: All other skin or soft tissue substitutes products for diabetic lower extremity ulcers not included above are considered experimental, investigational, and unproven due to insufficient evidence in the peer reviewed medical literature to support their clinical effectiveness and validity of successful health outcome and are therefore not medically necessary.
4. For both DFU and VLU an implemented treatment plan to be continued throughout the course of treatment demonstrating all the following.
   • Debridement as appropriate to a clean granular base.15,16
   • Documented evidence of offloading for DFU and some form of sustained compression dressings for VLU
   • Infection control with removal of foreign body or nidus of infection
   • Management of exudate with maintenance of a moist environment (moist saline gauze, other classic dressings, bioactive dressing, etc.)
   • Documentation of smoking history, and counselling on the effect of smoking on wound healing. Treatment for smoking cessation and outcome of counselling, if applicable.
5. The medical record documentation must include the interventions having failed during prior ulcer evaluation and management. The record must include an updated medication history, review of pertinent medical problems diagnosed since the previous ulcer evaluation, and explanation of the planned skin replacement with choice of skin substitute graft/cellular tissue product (CTP) product. The procedure risks and complications must also be reviewed and documented.
6. The patient is under the care of a qualified provider for the treatment of the systemic disease process(es) etiologic for the condition (e.g., venous insufficiency, diabetes, neuropathy) and documented in the medical record.
   *Services provided within the policy coverage indications will be considered reasonable and necessary when all aspects of care are within the scope of practice of the provider’s professional licensure; and when all procedures are performed by appropriately trained providers in the appropriate setting.

When Coverage Will Not be Approved

This policy is for the use of Bioengineered Skin and Soft Tissue Substitute for Diabetic Neuropathic Foot Ulcers, Vascular Insufficiency Ulcer and Chronic Pressure Non-Healing Wounds only.

All other uses of the skin and soft tissue substitute products not listed in this policy are considered experimental, investigational and/or unproven due to insufficient evidence in peer reviewed medical literature to determine the clinical effectiveness and validity of successful health outcome and are therefore considered not medically necessary including but not limited to:

• Mohs Micrographic Surgery - Use of skin and tissue substitute products following Mohs micrographic surgery.
• Surgical Repair of Hernias or Parastomal Reinforcement
• Amniotic membrane, amniotic fluid or other placental derived products injections and/or applications as a means of managing musculoskeletal pain, injuries, joint conditions, and all other musculoskeletal conditions (See MAC appropriate LCD for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound).
• All other uses reviewed herein of the human amniotic products (e.g., derived from amnion, chorion, amniotic fluid, umbilical cord, or Wharton's jelly) not listed above are considered investigational.

Limitations: (per ulcer episode of care)

The following are considered NOT reasonable or necessary:

• Greater than eight (8) applications of a skin substitute graft/CTP within the episode of skin replacement therapy (defined as sixteen (16) weeks from the first application of a skin substitute graft/CTP). In exceptional cases in which 8 applications are not sufficient for adequate wound healing, additional applications may be considered with documentation that includes progression of wound closure under current treatment plan and medical necessity for additional applications subject to Plan Medical Director review.
• Repeat applications of skin substitute graft/CTP when a previous application was unsuccessful. Unsuccessful treatment is defined as increase in size or depth of an ulcer, no measurable change from baseline, and no sign of improvement or indication that improvement is likely (such as granulation, epithelialization, or progress towards closure). Unsuccessful therapy also includes reoccurrence of the ulcer in the same location within 12 months from initial application.
• Application of skin substitute graft/CTP in patients with inadequate control of underlying conditions or exacerbating factors, or other contraindications (e.g., active infection, progressive necrosis, active Charcot arthropathy of the ulcer extremity, active vasculitis, ischemia).
• Use of surgical preparation services (e.g., debridement), in conjunction with routine, simple or repeat skin replacement surgery with a skin substitute graft/CTP).
• Excessive wastage (discarded amount). The skin substitute graft/CTP must be used in an efficient manner utilizing the most appropriate size product available at the time of treatment. It is expected that use of product, size and preparation should conform to that most closely fitting the wound with the least amount of wastage.
• All liquid or gel skin substitute products or CTPs for ulcer.
• Placement of skin substitute graft/CTP on infected, ischemic, or necrotic wound bed.

The Plan may compare the cost-effectiveness of alternatives when determining which products will be covered.

Billing/ Coding/physician Documentation Information

This policy may apply to the following codes.  Inclusion of a code in the section does not guarantee reimbursement.

Applicable Codes: See Chart Below

Current Procedural Terminology (CPT) defines skin substitute grafts to include non-autologous skin (dermal or epidermal, cellular, or acellular) grafts (e.g., homograft, allograft), non-human skin substitute grafts (i.e., xenograft), and biological products that form a sheet scaffolding for skin growth. CPT does not include non-graft wound dressings (e.g., gel, powder, ointment, liquid) or injectable skin substitutes in the skin substitute graft codes.

HCPCS codes included in this list are FDA approved/ meeting necessary regulatory requirements for CTPs for chronic ulcer treatment as of publication. Each product has specific designated approved usage. This is not an all-inclusive list of CTPs as new products and HCPCS codes will be considered for coverage if meeting the regulatory requirements and criteria. Therefore, any HCPCS code that is not included in this list will not be separately reimbursed.

The above medical necessity criteria MUST be met for the following codes to be covered:

Group 2 below lists HCPCS skin substitute grafts/CTP codes for Diabetic Foot Ulcers (DFU) ONLY and must be reported on the same claim as a CPT/HCPCS application code in Group 1 above.

A HCPCS code from the Group 3 Codes in the table below must be reported with a CPT/HCPCS code from the Group 1 Codes above. Group 3 Codes

The following HCPCS codes listed in Group 4 codes are non-covered:

Group 4 Codes

Special Notes

The issuance of a CPT/HCPCS code or FDA approval for a specific indication does not mean that a product or service is medically reasonable and necessary. The FDA determines safety and effectiveness of a device or drug but does not establish medical necessity. While Medicare may adopt FDA determinations regarding safety and effectiveness, Medicare or Medicare contractors determine whether the drug or device is reasonable and necessary for the Medicare population under §1862(a)(1)(A).

Billing for skin substitute application procedures is required to also include the appropriate high cost or low-cost skin substitute products.

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

References:

1. Blue Cross and Blue Sheild NC Corporate Policy Skin and Soft Tissue Substitutes; Originated January 1994 via Skin and Soft Tissue Substitutes | Providers | Blue Cross NC accessed on 08/11/2025
2. Proposed LCD-Skin Substitute Grafts/Cellular and Tissue-Based Products for the Treatment of Diabetic Foot Ulcers and Venous Leg Ulcers (DL39806) accessed on 8/11/2025
3. Proposed Local Coverage Article (LCA) Billing and Coding: Skin Substitutes Grafts/Cellular Tissue-Based Products for the Treatment of Diabetic Foot Ulcers and Venous Leg Ulcers Draft Article - Billing and Coding: Skin Substitutes Grafts/Cellular Tissue-Based Products for the Treatment of Diabetic Foot Ulcers and Venous Leg Ulcers (DA59740 )accessed on 8/11/2025
4. BCBS of Michigan Medical Policy –Skin and Soft Tissue Substitutes Medicare Advantage; effective date 04/11/2025; Accessed on 08/28/2025 via chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.bcbsm.com/amslibs/content/dam/public/mpr/mprsearch/pdf/2191560.pdf
5. Humana Medicare Advantage Medical Policy – Skin and Tissue Substitutes; effective date - 08/01/2025; accessed on 8/28/2025 via  https://mcp.humana.com/tad/tad_new/Search.aspx?sortfield=name&policyType=medical
6. Regence (MA) Medicare Advantage Policy – Bioengineered Skin and Soft Tissue Substitutes and Amniotic Products effective date 07/01/2025 accessed on 8/28/2025 via https://www.regence.com/provider/library/policies-guidelines/medical-policy/ma-medical-policy

Policy Implementation/Update Information:

Revision Dates: 

01/05/2026: Newly created policy in absence of current NCD, LCD and LCA. Notification given (1/30/26) for Effective Date 5/1/26. (AR)

Approval Dates: 

Medical Coverage Policy Committee: January 2026

Physician Advisory Group Committee: