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CurrentAetnaPolicy 0244

Skin and Soft Tissue Substitutes

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Aetna's clinical policy on the medical necessity and investigational status of skin and soft tissue substitute products for wound care, specifying indications where particular products are considered medically necessary and listing products deemed experimental/investigational. Affects providers treating wounds, burns, diabetic foot ulcers, venous ulcers, and surgical reconstruction.

Policy Summary

PayerAetna

PolicySkin and Soft Tissue Substitutes

Policy CodePolicy 0244

Change TypeNo material change

Effective DateMay 28, 1998

Last ReviewFeb 9, 2024

Next Review DateFeb 22, 2024

Key ActionObtain prior authorization when using covered skin or soft tissue substitutes to document that product selection and wound characteristics meet the policy's medical necessity criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Multiplenamed medically necessary

350+experimental/investigational

Listedrelated policies

20+product HCPCS/Q-codes

Coverage Criteria and Evidence Summaries

Medically Necessary Indications (selected examples)

Covered when ALL of the following are met for the specified product:

Alloderm / Alloderm-RTU: Use is for one of the following: (1) breast reconstructive surgery; (2) surgical repair of complex abdominal wall wounds (e.g., due to infection or fascial defect); (3) ear drum augmentation (tympanoplasty), repair of skull base defect, or temporal bone lining.

All other indications are considered experimental/investigational.

Allogeneic human, cadaver-derived skin graft (AlloSkin / AlloSkin AC/RT): Used for management of traumatic skin wounds and burn wounds when the wound is too large for autograft.

AlloSkin AC and AlloSkin RT have particular processing/usage characteristics; see product-specific entries.

AmnioBand / EpiFix / Grafix / DermACELL / Epicord / TheraSkin and similar allografts: Treatment of partial or full-thickness neuropathic diabetic foot ulcers > 6 weeks duration with no capsule/tendon/bone exposed when used in conjunction with standard diabetic ulcer care; and for difficult-to-heal chronic venous partial or full-thickness lower-extremity ulcers that have failed ≥4 weeks of standard wound therapy when indicated for that product.diabetic foot ulcer >6 weeks; venous ulcer failed ≥4 weeks

Product-specific HCPCS/Q-codes and matching ICD-10 diagnosis codes must be used when applicable.

Apligraf (Graftskin): Use with standard diabetic foot ulcer care for full-thickness neuropathic DFUs >6 weeks without tendon/muscle/capsule/bone exposure, OR with standard therapy for chronic, non-infected partial or full-thickness venous stasis ulcers that have failed ≥4 weeks of conservative measures (including compression).diabetic foot ulcer >6 weeks; venous ulcer failed ≥4 weeks

Consistent with FDA PMA indications; not medically necessary when inadequate blood supply to the involved foot is present.

Dermagraft: For full-thickness diabetic foot ulcers >6 weeks duration that extend through the dermis but without tendon/muscle/joint capsule/bone exposure; or for wounds related to dystrophic epidermolysis bullosa.>6 weeks

Use with standard wound care; contraindicated in infected ulcers and ulcers with sinus tracts and not medically necessary in persons with inadequate blood supply to the involved foot.

Epicel (cultured epidermal autograft): For deep dermal or full-thickness burns comprising total body surface area (TBSA) ≥ 30%; may be used with or instead of split-thickness autografts when autograft is not feasible.TBSA >= 30%

Experimental / Investigational Products

Not covered — considered experimental and investigational due to inadequate evidence:

Listed products: Specific products enumerated in the policy’s experimental/investigational list (extensive numbered list including ACM Surgical Collagen, ActiGraft, numerous amniotic/placental-derived products, many brand-name allografts and matrices) are considered experimental and investigational because clinical effectiveness has not been established.

See policy product list for full entries and numbering.

Covered when selection criteria are met for product-specific indications

Products listed with HCPCS/Q-codes are covered when the policy's selection criteria for that product and indication are met.

Coverage prerequisite: The product-specific HCPCS/Q-code must be billed and the submitted ICD-10 diagnosis code must match an indication listed for that product in the policy (e.g., diabetic foot ulcer, chronic venous ulcer, burns, epidermolysis bullosa).

Examples of covered HCPCS/Q-codes and linked ICD-10 codes are provided in the coding section (chunks 21,23,24,28-31).

Not covered / Experimental or investigational

Products explicitly identified as experimental and investigational in this section are not covered for indications listed.

Experimental/Investigational list not covered: Use of products included in the policy's experimental/investigational list (see sections enumerating numerous products and associated HCPCS/A-codes) is considered investigational and therefore not covered for the CPB-listed indications.

Many corresponding HCPCS A-codes are listed as not covered; providers should not bill these codes for covered indications.

Evidence limitations for clinical effectiveness

Evidence summary and limitations

Systematic review findings: A systematic review identified 76 commercially available skin substitutes; 3 systematic reviews and 22 RCTs examined 16 distinct skin substitutes in DFUs, pressure ulcers, and venous leg ulcers; most studies did not report patient-centered outcomes and overall evidence quality is limited.

Authors concluded better-designed studies with clinically relevant endpoints are needed.

Outcome reporting limitations: Clinical studies infrequently reported outcomes such as amputation, wound recurrence ≥2 weeks after treatment, return to function, pain, exudate, or odor, limiting assessment of meaningful clinical benefit.

These limitations affect generalizability and strength of coverage conclusions.

Manufacturer indications and evidence notes

Product-specific information (manufacturer-stated indications)

ACM Surgical Collagen (sheet): Manufacturer indicates use as a scaffold for management of partial- and full-thickness wounds after wound bed preparation; supplied as sterile single-use sheets in specified sizes.

Applied after removal of necrotic debris and biofilm; usually one matrix per application but repeat applications may be used.

ACM Surgical Extra Advanced Collagen Powder: Manufacturer indicates use for wound management of partial- and full-thickness wounds; supplied as sterile single-use pouches/vials and applied after wound site preparation.

Available in multiple vial/pouch sizes per manufacturer labeling.

ActiGraft: FDA-cleared to create autologous blood-clot tissue from a patient’s whole blood to serve as a biologic scaffold; clinical trial in DFUs was recruiting and published peer-reviewed evidence is lacking to support routine clinical use.

Clinical trial NCT04185558 listed with estimated completion 2022; lack of peer-reviewed evidence for chronic DFU treatment.

Evidence summaries and considerations

Evidence‑based considerations and product‑specific summaries

ActiGraft evidence summary: ActiGraft is FDA-cleared for producing autologous clot tissue but there is a stated lack of evidence supporting its effectiveness for chronic DFUs or other indications.

Ongoing trial noted; peer-reviewed effectiveness data are lacking.

HSAM / Affinity evidence: Preclinical and small clinical series show biologic activity; one RCT (Serena et al 2020) reported greater DFU closure at 12 and 16 weeks versus SOC with increased probability of closure (HR 1.75), but authors call for further prospective and cost-effectiveness studies.

RCTs exist but broader comparative and long-term data are needed.

AlloDerm evidence considerations: AlloDerm has varied outcomes across indications: used in burns, breast reconstruction, abdominal wall/hernia repair and skull base reconstruction, with limited comparative evidence and reports of disappointing long-term results for some hernia repairs.

Comparative and long-term data are limited; evidence strength is generally low.

Abdominal Wall Reconstruction — evidence-informed considerations

Clinical evidence and outcomes-based considerations when using ADM/biologic mesh for abdominal wall reconstruction

Preferred repair goals: Primary fascial coaptation with mesh reinforcement is preferred and is associated with fewer hernia recurrences and complications compared with bridged repairs.

Studies report bridged repair recurrence rates substantially higher (e.g., 56% vs 8%) and HR ~9.5 in some series.

Factors associated with higher recurrence/complications: Bridged repair technique; defect width > 15 cm; use of human cadaveric ADM in some series; smoking; BMI ≥ 30 kg/m2; coronary disease; wound skin dehiscence.>15 cm

These factors were identified as predictors in multi-variable analyses and cohort studies.

Long-term outcome assessment: When assessing durability of ADM use, consider follow-up of at least 36 months to capture hernia recurrence and surgical-site occurrences.>=36 months

Other indications (breast reconstruction, parotidectomy, tympanoplasty)

Evidence regarding AlloDerm for non-hernia indications

Breast reconstruction: Published evidence consists mainly of small case series; no clear comparative data demonstrating improved aesthetic outcomes with AlloDerm and limited follow-up for long-term complications.

Randomized trials are ongoing.

Prevention of Frey syndrome after parotidectomy: Systematic reviews and meta-analyses report substantial relative risk reductions in objective and subjective incidence of Frey syndrome and lower salivary fistula rates with acellular dermis grafts compared with no graft.

Further RCTs recommended despite favorable pooled results.

Other surgical reconstructions: AlloDerm has been used for tympanoplasty and skull base repairs with small RCTs or case series reporting comparable graft success and epithelialization in selected settings; evidence varies by indication.

Sample sizes and follow-up are often limited.

Documented clinical indications and evidence

Documented clinical indications and evidence: Clinical uses supported by cited evidence include: complex abdominal wall/hernia repair (Strattice, AlloMax), skull base and mastoid cavity reconstruction (AlloDerm), treatment of non-healing DFUs (HR-ADM/AlloPatch RCTs), rotator cuff augmentation (case series), and temporary skin replacement for burns and chronic wounds (AlloSkin).

Evidence strength varies by product and indication; randomized data exist for selected products (e.g., HR-ADM in DFUs).

dHACA / AmnioBand evidence-based considerations

RCT-supported use: Aseptically processed dehydrated human amnion and chorion allograft (dHACA/AmnioBand) has randomized controlled trial evidence showing superior 12-week wound closure rates versus standard of care and versus tissue-engineered skin substitutes in non-healing DFUs and in venous leg ulcers.

Trials used a 2-week SOC run-in prior to randomization; healing rates reported up to ~85–90% at 12 weeks in some trials.

Reported clinical endpoints: Endpoints reported in trials include proportion healed at 6 and 12 weeks, mean time to heal, number of grafts per healed wound, product cost to heal, and percentage wastage.

Examples: mean product cost to heal DFU reported ~$1,400–$2,200 and wastage percentages reported (e.g., ~36–40%).

Evidence limitations: Limitations across dHACA trials include open-label designs, selective withdrawal rules for nonresponders, relatively small sample sizes, and limited comparisons across different tissue forms.

These limitations may affect generalizability despite positive RCT results.

Non-dHACA allografts: use and evidence

Other allograft products (AlloSkin, AlloWrap, PureSkin, etc.):

Product use descriptions: Various allograft products are described as temporary skin replacements or scaffolds for burns, trauma, and chronic wounds; application methods include surgical anchoring or topical placement and product processing/sterilization methods differ by manufacturer.

Product sizes, supply formats, and processing (e.g., e-beam irradiation) vary and affect clinical handling.

Evidence status: Clinical evidence for many non-dHACA allografts is limited or mixed and often consists of small case series or retrospective reports; some products lack peer-reviewed evidence of effectiveness.

Providers should consider evidence availability when proposing use of these products.

Background and evidence summaries (no coverage rules in this segment)

Background summaries only: This section contains background descriptions and evidence summaries for multiple amniotic/placental products and does not define explicit coverage decision criteria within this segment.

Refer to product-specific coverage entries elsewhere in the policy.

Apligraf – FDA-indicated use context

Covered when ALL of the following are met

Apligraf indications and prior therapy: Apligraf is FDA PMA-approved for noninfected partial and full-thickness skin ulcers due to venous insufficiency (>1 month duration) not adequately responsive to conventional therapy and for diabetic foot ulcers; clinical use should align with these indications and prior conservative management (e.g., compression for venous ulcers) should have failed before use.venous ulcer >1 month; DFU >6 weeks

Insufficient evidence to extend Apligraf coverage to pressure sores, dermatologic surgery wounds, or burns at this time.

Amniotic/placental-derived products – investigational/conditional

Considered investigational or insufficient evidence when used for:

AM-derived applications with limited evidence: Amniotic/placental-derived products used for orthopedic sports medicine (tendon/ligament injuries, cartilage defects, osteoarthritis) and numerous operative adjuvant indications have promising preclinical and early clinical data but lack high-level human evidence; formulations and processing vary markedly across products, affecting outcomes.

Further clinical trials are required to define safe and effective indications.

Artelon – insufficiency of evidence for many indications

Not established/insufficient evidence for coverage for the following surgical indications

Artelon applications without sufficient evidence: Available evidence is insufficient to support Artelon for ACL reconstruction, rotator cuff repair, trapezio-metacarpal (TMC) osteoarthritis, and other listed surgical indications; published trials are small or low quality.

Use is considered unestablished pending higher-quality data.

Evidence summaries — informational

Evidence summaries and intended indications described for individual products (informational):

ArthroFlex (FlexGraft) evidence: Manufacturer describes ArthroFlex for chronic wounds and large surgical wounds; peer-reviewed literature largely reports biomechanical and Level III–IV clinical series for orthopaedic augmentations with variable healing and functional outcomes.

Evidence level is modest and often limited to nonrandomized series.

Artiss evidence: Artiss fibrin sealant is FDA-approved for attaching skin grafts in burn patients based on a phase III randomized trial demonstrating non-inferiority to staples for wound closure at day 28 with favorable secondary outcomes.

Product-specific trial support exists for the burn grafting indication.

Autologous platelet-derived products: Autologous PRP/APG/APC and platelet-derived growth factor preparations have been judged by CMS and guideline assessments to have insufficient evidence for treatment of chronic non-healing cutaneous wounds; national non-coverage decisions exist.

CMS non-coverage and subsequent reconsiderations cited lack of sufficient evidence.

Described intended uses (informational)

Intended clinical uses described (informational):

Described intended uses: Products are described for repair or replacement of lost or damaged dermal tissue; wound covering for traumatic injuries, burns, surgical wounds (including Mohs), chronic wounds (diabetic, venous, arterial, pressure ulcers), wounds with exposed vital structures (tendon, bone, blood vessels), adhesion barrier, and select ocular/other reconstructions.

Clinical effectiveness evidence varies by product; product size, formulation, and hydration state affect application and dosing.

Product-specific intended use and evidence considerations

Coverage depends on product-specific intended indications, demonstrated safety/effectiveness, and adequate documentation of clinical need.

Conexa intended use: Conexa Reconstructive Matrix is intended to reinforce soft tissue repaired by sutures or suture anchors during tendon repair surgery and to repair body wall defects; cleared via 510(k) but peer-reviewed evidence beyond case reports is limited.

Product is supplied in specific sizes; evidence insufficiency may limit coverage to specified indications and documented medical necessity.

MatriStem/Cytal intended use: MatriStem/Cytal products (UBM) are intended for management of partial and full-thickness wounds, pressure/venous/diabetic ulcers, tunneled/undermined wounds, and surgical/trauma wounds; supplied as sheets or micronized powder and cleared via 510(k).

Evidence and product forms vary; powder form evidence is limited.

Products with limited evidence: Several products (e.g., CoreCyte, Corplex/Corplex P, Cryo-Cord) are described as having limited or no peer-reviewed evidence; absence of supporting clinical data may support designation as experimental/investigational for CPB indications.

Requests for coverage should include robust supporting documentation when available.

Use of AlloDerm for indications other than the specific reconstructive and repair uses listed in this policy (for example, off‑label applications not enumerated under the product’s covered indications) is considered experimental/investigational and is not supported by the clinical evidence presented in this document.

Examples of ICD‑10 conditions called out in the policy as not appropriate for coverage of skin and soft tissue substitute applications include gangrene (I96), necrotizing fasciitis (M72.6), osteomyelitis (M86.x), and osteonecrosis (M87.x); these and other specified infectious, malignant, or otherwise excluded diagnoses are listed in the CPB as not covered for the indicated substitute uses.

The policy enumerates numerous procedure and HCPCS/CPT/ICD‑10 codes that are specifically flagged as not covered for the CPB indications. Examples cited include HCPCS codes such as Q4108 and Q4114, certain C‑codes (e.g., C9358), broad CPT ranges for surgical procedures (e.g., 20100–29999, 10040–19499), and ICD‑10 code groups for pressure ulcers and selected musculoskeletal or ocular wound codes; use of these codes for excluded indications may result in denial.

ActiGraft is described as an FDA‑cleared system that creates an autologous in‑vitro blood clot tissue scaffold, but the document states there is a lack of evidence to support ActiGraft for the treatment of chronic diabetic foot ulcers or other indications; a clinical trial was recruiting as of the cited update but peer‑reviewed effectiveness data are not available.

When planning abdominal wall reconstruction, the policy emphasizes that bridged repairs (mesh used to span fascial edges without primary fascial coaptation) are associated with substantially higher recurrence and complication rates and therefore should be avoided when primary fascial coaptation with mesh reinforcement is feasible; documentation should support the planned technique and rationale if bridged repair is proposed.

A contemporary UpToDate review on operative management of anorectal fistulas does not list AlloDerm or acellular cadaveric dermis as a management option, indicating the literature and guideline sources cited in this policy do not support AlloDerm for anorectal fistula repair.

Several amniotic/placental‑derived products are noted as having no peer‑reviewed published studies evaluating safety or efficacy. Examples specifically called out as lacking published evidence include AmnioArmor, AmnioBind, and AmnioCyte Plus.

This segment of the document does not provide blanket exclusions for all named products, but it repeatedly documents that many individual products are described as having a lack of supporting peer‑reviewed evidence; absent adequate clinical data, these products are presented as investigational or unsupported for routine coverage.

Although Apligraf has FDA‑approved indications for certain venous and diabetic ulcers, the policy indicates there is insufficient information to extend coverage for other uses such as treatment of pressure sores, dermatologic surgery wounds, and burns at this time.

The policy references the CMS national non‑coverage determination and subsequent CMS decisions concluding insufficient evidence for platelet‑derived wound healing formulas; autologous platelet‑rich plasma and similar platelet‑derived products are cited as having insufficient evidence for coverage in chronic non‑healing cutaneous wounds per the CMS determinations.

Biobrane is described as a biosynthetic dressing that requires adherence to the wound bed; the policy notes that very deep wounds or wounds with high bacterial counts will not allow Biobrane adherence, making it unsuitable for those clinical situations.

The document identifies multiple products for which there is a stated lack of evidence regarding effectiveness. Examples include carePATCH and Celera products (e.g., celera Dual Membrane and celera Dual Layer), which the policy flags as unsupported by peer‑reviewed data.

Several products are noted as having no peer‑reviewed published studies evaluating safety and efficacy and therefore are described as lacking evidence; examples include Cellesta Amniotic Membrane, Cellesta Flowable Amnion, Cellesta Cord, Coll‑e‑Derm, and Cogenex.

Conexa Reconstructive Matrix is specifically noted to have insufficient evidence beyond case reports to support its safety and effectiveness; the policy indicates Conexa may be considered unsupported absent higher‑quality data.

Dermagraft is considered not medically necessary in persons with inadequate blood supply to the involved foot and is contraindicated in infected ulcers and ulcers with sinus tracts; other products such as Epicel are recognized as covered only for their specific listed indications, with other uses considered investigational.

Products and HCPCS codes that are explicitly listed in the policy’s experimental/investigational lists or the HCPCS codes not covered sections are treated in the document as not medically necessary for the CPB‑listed indications and may be denied if billed for those uses.

The policy highlights limited and low‑quality evidence across many skin and soft tissue substitute products, noting that few studies report clinically important patient‑centered outcomes (amputation, recurrence, pain, function) and that better‑designed trials are needed before broad clinical adoption.

Use of AlloDerm and other biologic meshes for some hernia and abdominal wall repairs is associated in cited reports with disappointing long‑term results in some series and with high cost and variable failure/recurrence rates; these evidence limitations are emphasized as reasons for cautious use and may influence coverage decisions.

For breast reconstruction, the policy states that AlloDerm lacks comparative evidence

Several studies cited in the policy have methodological limitations (risk of bias, small sample sizes, animal‑model data) that the document notes may preclude generalizing results and support the designation of some applications as investigational until higher‑quality evidence is available.

The policy explicitly states there is insufficient evidence to establish effectiveness for products such as AmnioArmor, AmnioBind, and AmnioCyte Plus, and repeatedly flags multiple amniotic‑derived products as lacking peer‑reviewed support.

Throughout the document multiple products are listed with statements of limited or absent evidence (for example, AmnioBind, AmnioCyte Plus, Amnio‑Maxx, Amniorepair/AltiPly, Amniotext), underscoring the policy’s conclusion that many commercial offerings lack peer‑reviewed data supporting clinical effectiveness.

Billing Codes and Code Lists

Covered HCPCS/Q codes for named products (if selection criteria met)HCPCSCovered

Q4101	Apligraf, per sq cm
Q4182	Transcyte, per sq cm
Q4100	Skin substitute, not otherwise specified
Q4105	Integra Dermal Regeneration Template (DRT), per sq cm
C9363	Integra Meshed Bilayer Wound Matrix, per sq cm
Q4104	Integra Bilayer Matrix Wound Dressing (BMWD), per sq cm
Q4116	Alloderm, per sq cm
Q4102	Oasis Wound Matrix, per sq cm
Q4107	Graftjacket, per sq cm
Q4115	AlloSkin, per sq cm

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ICD-10 diagnosis codes associated with covered indicationsICD-10

E08.621	Diabetes mellitus due to underlying condition with foot ulcer
E09.621	Drug or chemical induced diabetes mellitus with foot ulcer
E10.621	Type 1 diabetes mellitus with foot ulcer
E11.621	Type 2 diabetes mellitus with foot ulcer
E13.621	Other specified diabetes mellitus with foot ulcer
T20.011A - T25.799S	Burns (various extensions)
I83.001 - I83.229	Varicose veins of lower extremities with ulcer (with/without inflammation)

HCPCS/other codes referenced (not covered or conditional)HCPCS

C5271 - C5278	Application of low cost skin substitute grafts (various sites)
C7500	Debridement, bone including epidermis, dermis, subcutaneous tissue, muscle and/or fascia, first 20 sq cm or less with manual preparation and insertion of deep drug-delivery device(s)
A4100	Skin substitute, FDA cleared as a device, not otherwise specified
A4575	Topical hyperbaric oxygen chamber, disposable
A6196 - A6199	Alginate or other fiber gelling dressing
A6206 - A6211	Contact layer and foam dressings
C1781	Mesh (implantable)
C9352 - C9354	Various implantable collagen/pericardial tissue matrices
G0428	Collagen meniscus implant procedure
P9020	Platelet rich plasma, each unit

HCPCS codes not coveredHCPCSNot Covered

A2001	InnovaMatrix AC, per sq cm (not covered)
A2002	Mirragen Advanced Wound Matrix, per sq cm (not covered)
A2003	Bio-connekt wound matrix, per sq cm (not covered)
A2004	XCelliStem, per sq cm (not covered)
A2005	Microlyte Matrix, per sq cm (not covered)
A2006	NovoSorb SynPath dermal matrix, per sq cm (not covered)
A2007	Restrata, per sq cm (not covered)
A2008	TheraGenesis, per sq cm (not covered)
A2009	Symphony, per sq cm (not covered)
A2010	Apis, per sq cm (not covered)

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C-codes and related HCPCS/CPT (partial list)HCPCS

C9250	Human plasma fibrin sealant, Artiss, 2ml
C9355	Collagen nerve cuff (neuromatrix), per 0.5 cm length
C9360	Dermal substitute, neonatal bovine origin, per 0.5 sq cm
C9364	Porcine implant, Permacol, per sq cm
C9358	SurgiMend Collagen Matrix, per 0.5 sq cm
C9356	Tenoglide Tendon Protector Sheet, per sq cm

Experimental and investigational products (examples)mixedExperimental

(various)—see list

Numerous named products listed in policy considered experimental/investigational when used outside supported indications

CPT ranges and codes not coveredCPTNot Covered

10040 - 19499	Surgery, integumentary system (not covered for certain indications)
20100 - 29999	Musculoskeletal system (not covered for prevention of adhesions after orthopedic surgery)
29806 - 29828	Arthroscopy, shoulder, surgical (selected not covered)
29806-29828	Arthroscopy shoulder range listed in policy
11950 - 11954	Subcutaneous injection of filling material (cosmetic)

ICD-10 codes referenced as not covered (partial list)ICD-10Not Covered

L89.000 - L89.95	Pressure ulcer (not covered)
H18.821 - H18.829	Corneal disorder due to contact lens (not covered)
T20.011A – T25.799S	Burns (not covered for some listed indications)
C43.0 - C43.9	Malignant melanoma of skin (not covered)
M86.00 - M86.9	Osteomyelitis (listed in exclusions)

Prior Authorization, Documentation, and Billing Guidance

Prior Authorization
Coverage conditional on selection criteria
Coverage of specific HCPCS/Q codes and products is conditional on meeting product-specific selection criteria; prior authorization may be required to confirm the indication and that selection criteria are met.
Confirm linkage of billed HCPCS/CPT codes to the documented diagnosis and selection criteria (e.g., Q4101 for Apligraf requires DFU or VLU diagnosis codes and meeting prior-therapy requirements).
Prior authorization should verify that product-specific eligibility rules (wound type, duration, depth, absence of exposed tendon/capsule/bone, and prior conservative care) are satisfied.

Billing Rule
Codes not covered for listed indications
Certain CPT/HCPCS and ICD-10 codes are listed as not covered for the indications in this CPB; billing these codes or codes that are non-covered for the listed indications may result in claim denial.

Background and Policy Scope

Background: Skin and soft tissue substitutes encompass acellular dermal matrices, allogeneic skin grafts, amniotic membranes, cultured skin equivalents, biosynthetic dressings, and other biologic or engineered products applied to burns, traumatic wounds, diabetic foot ulcers, venous stasis ulcers, and reconstructive surgical sites; indications and the strength of evidence vary widely by product and intended use.

Definitions and Key Terms

Neuropathic diabetic foot ulcer — definition and criteria

DefinitionPartial or full‑thickness neuropathic diabetic foot ulcers >6 weeks' duration with no exposed capsule, tendon, muscle, joint capsule, or bone; managed in conjunction with standard diabetic ulcer care.

Typical exclusionsInfected ulcers, ulcers with inadequate blood supply, and ulcers with exposed tendon/muscle/joint capsule/bone are excluded from indicated use in many products (e.g., Apligraf, DermACELL).

Coverage implicationMany listed skin substitutes are covered for DFUs only when these specific criteria and prior standard care requirements are met.

Difficult-to-heal chronic venous ulcer — definition and criteria

DefinitionChronic venous partial or full‑thickness lower‑extremity ulcers that have failed standard wound therapy of at least 4 weeks' duration (including regular dressing changes and compression).

Policy Summary

PayerAetna

PolicySkin and Soft Tissue Substitutes

Policy CodePolicy 0244

Change TypeNo material change

Effective DateMay 28, 1998

Last ReviewFeb 9, 2024

Next Review DateFeb 22, 2024

Key ActionObtain prior authorization when using covered skin or soft tissue substitutes to document that product selection and wound characteristics meet the policy's medical necessity criteria.

SourceLink

On This Page

Biologic mesh/ADM evidence summary: Biologic grafts demonstrate variable failure rates dependent on material and processing; evidence levels are generally low and long-term durability and cost-effectiveness are uncertain.

Reported failure rates: SIS ~6.7% at 19 months; AHD ~13.6% at 12 months; cumulative recurrence at 3–5 years reported in some cohorts.

Cumulative recurrence rates reported at 3 and 5 years (e.g., 11.5% and 14.6% in one cohort).

Other product summaries: Multiple manufacturer-stated indications and small clinical studies are described for various products (e.g., Avomentin, AxoBioMembrane), but high-quality comparative evidence is generally limited.

These summaries are informational and not coverage rules.

Fistula plug use: Biologic fistula plugs have limited case-series evidence; because non-operative management closes many fistulas (60–70% over 6–8 weeks), conservative therapy is generally preferred before implantable plugs.

Consider conservative management prior to plug use.

Review the policy's code lists: examples of not-covered HCPCS/CPT include L8658 and specified CPT codes (see CPB code list).
ICD-10 codes enumerated as not covered (e.g., pressure ulcers L89.x, certain infection codes) should not be used to justify coverage for listed products.

Prior Authorization
Limited evidence; prior authorization prudent
Evidence for many products and indications is limited, heterogeneous, or based on small series/retrospective studies; when evidence is insufficient or of low quality, prior authorization and additional documentation are prudent.
Products with limited supporting evidence (e.g., CoreCyte, Coll-e-Derm, Conexa, Cryo-Cord, Corplex, Corplex P) typically require case-specific review and may be denied without adequate clinical justification.
Evidence gaps (including for powder formulations such as MatriStem/Cytal powder) may trigger requests for supplemental information or noncoverage determinations.

Prior Authorization
Preauthorization considerations for ADM/biologic mesh
For acellular dermal matrices (ADM) and other biologic meshes used in abdominal wall reconstruction and similar surgeries, prior authorization is recommended to confirm indication, planned surgical approach, and rationale for choosing biologic material over alternatives.
Document whether primary fascial coaptation will be attempted or whether a bridged repair is planned; preference is for mesh-reinforced primary fascial coaptation when feasible.
If an implantable or size-specific allograft/mesh is proposed, provide the product name, 510(k)/PMA status, size, and intended use to support medical necessity.

Step Therapy
Prior conservative therapy and trial-based evidence
Randomized trials of several advanced skin substitutes required a trial of standard of care (SOC) during a pre-randomization screening period; prior conservative therapy should be documented before authorizing advanced products.
Trials typically required a 2-week (or 4-week for venous ulcers) SOC screening period with offloading, debridement, and standard moist wound care prior to randomization.
Prior authorization should confirm documentation of failed conservative therapies for the required duration (e.g., DFU >6 weeks of inadequate response; VLU >4 weeks failed compression therapy).
Apligraf and similar products have FDA-labeled indications that align with requiring prior conservative therapy — authorization should reflect FDA labeling when applicable.

Prior Authorization
Prior authorization aligns with FDA-approved indications
Authorization decisions should align with FDA-approved indications (for devices with PMA/approved labeling). Requests for off-label indications should be supported by robust peer-reviewed evidence or will be considered investigational.
Apligraf approval requires use with standard diabetic foot ulcer care or for venous leg ulcers per labeling; prior authorization should confirm labeled indication.
Document when a product is being used within FDA-approved indication versus off-label use; off-label requests warrant additional clinical justification.

Documentation Required
Clinical suitability and documentation
Clinical suitability and comprehensive documentation must accompany requests for coverage of skin and soft tissue substitutes.
Document wound characteristics (anatomic site, dimensions in cm2, depth), presence/absence of exposed tendon/capsule/muscle/bone, signs of infection, vascular status (e.g., ABIs), and comorbidities impacting healing.
Describe prior standard-of-care measures attempted and their duration (debridement, offloading, compression, glycemic control).
Specify number of anticipated applications and prior product usage (if any).

Prior Authorization
Prior authorization recommended for implantable/size-specific allografts
Implantable or size-specific allografts and sheets often require prior authorization to confirm the intended implant indication, size, and rationale for use.
Provide product-specific information: device name, formulation, size used, and whether implantation or reinforcement is intended (e.g., Strattice, AlloDerm, Conexa).
For Cytal/MatriStem and similar products, specify the exact variant (wound sheet, surgical matrix, micromatrix, or powder) and the wound indication.

Prior Authorization
Prior authorization: product-specific indication required
Some products have 510(k) clearances, PMA approvals, or product-specific intended uses; prior authorization should confirm the product is being used consistent with its cleared/approved intended use.
Identify the product and its regulatory status and provide the intended use to demonstrate concordance with the clearance/approval.
If product labeling limits use to specific wound types, document that the request matches labeling; if not, provide clinical evidence supporting off-label use.

Documentation Required
Specify Cytal/MatriStem variant and wound indication
Specify the exact Cytal/MatriStem variant and wound indication in authorization requests; different formulations (sheets, micromatrix, powder, surgical matrix) have different intended uses and evidence bases.
State whether the request is for MatriStem/Cytal wound sheets, surgical matrix (implantable), micromatrix, or powder and provide the wound type, size, and depth.
Note that MatriStem/Cytal powder has limited published evidence and may be subject to additional review or noncoverage.

Denial Risk
Indication mismatch / Experimental or investigational risk
Use of a product for indications not listed as medically necessary in this CPB is considered investigational; such requests are at high risk for denial absent compelling evidence.
If the indication is not among those the policy deems medically necessary (e.g., AlloDerm for hernia repair in some contexts), include strong peer-reviewed clinical evidence to support the request.
Be aware that experimental/investigational designations in the CPB will often result in denial unless exceptional circumstances are documented.

Denial Risk
Products with evidence-related denial risk
Specific products named in the CPB have been identified as lacking sufficient evidence; claims for these products may trigger denial or requests for additional clinical information.
Examples include carePATCH, Celera products, Cogenex, Coll-e-Derm, Conexa, CoreCyte, Corplex/Corplex P, Cryo-Cord, and other products listed under 'experimental and investigational' in the CPB.
For carePATCH and Celera, the CPB notes a lack of evidence; prior authorization should be supported by robust outcome data or will likely be denied.

Denial Risk
Noncovered codes and evidence limitations may trigger denial
Noncovered or unsupported codes and evidence limitations may lead to claim denial or retrospective review; accurate coding and robust documentation reduce denial risk.
CMS noncoverage determinations (e.g., for platelet-derived wound healing formulas/PRP) should be considered when submitting claims; these products have historical noncoverage.
Coding-dependent coverage: ensure CPT/HCPCS codes reflect the product and the clinical setting (application codes vs implantable mesh codes) and that ICD-10 diagnosis codes support the medical necessity.

Note
Evidence quality and utilization considerations
When randomized trial evidence exists, the quality and risk-of-bias assessments affect coverage determinations; cite trial design elements and assessments in authorization requests.
AHRQ and other evidence assessments have judged some trials (e.g., Zelen et al.) at moderate risk of bias — include trial limitations and comparative data when relying on published studies.
Utilization and cost findings (e.g., high wastage rates, product costs to closure) from trials should be documented as part of the clinical and economic rationale for use.

Denial Risk
Insufficient published evidence / evidence gap for powder form
Products or formulations with insufficient published evidence (including powder forms) may require additional review and are candidates for noncoverage absent persuasive data.
MatriStem/Cytal powder and other powder formulations are noted to have limited evidence and may be denied or require supplemental clinical documentation.
Products with only case reports or manufacturer claims (e.g., some novel allografts) will commonly be subject to denial or clinical review.

Documentation Required
Adjunctive use and contraindications
Adjunctive use and contraindications: many products are intended to be used in addition to standard wound care and have product-specific contraindications that must be documented.
Document that advanced products are being used as adjuncts to standard care (debridement, offloading, compression, infection control) as required by labeling (e.g., Dermagraft, Apligraf).
Contraindications such as inadequate blood supply, active infection, or presence of sinus tracts should be explicitly evaluated and recorded.

Billing Rule
Code-to-diagnosis linkage
Code-to-diagnosis linkage: ensure claims link the product/application code to appropriate ICD-10 wound or burn diagnosis codes and match selection criteria.
Examples: Q4101 (Apligraf) must be linked to diabetes with foot ulcer (E10.621 etc.) or venous ulcer codes (I83.x) when used for those indications.
Avoid using excluded ICD-10 codes (e.g., infection codes, pressure ulcer codes when not covered) to justify advanced graft application.

Documentation Required
Wound preparation documentation
Wound preparation and application documentation expected by manufacturers and reviewers should be provided with authorization requests.
Record wound bed preparation steps (debridement, removal of devitalized tissue and biofilm) and that hemostasis and appropriate cleansing were achieved prior to graft application.
Describe fixation/attachment method (sutures, adhesives) and whether graft was applied wet or dry, and number/size of grafts used.

Documentation Required
Suggested documentation to support use
Suggested documentation to support use: include long-term follow-up data, defect size, comorbidities, prior therapies, product lot/size, and number of applications to substantiate medical necessity.
Provide wound dimensions (length, width, calculated cm2), exposed structures, vascular assessment (ABI/TBI), HbA1c, and smoking status.
List product name, manufacturer, lot number (if available), formulation (sheet, injectable, powder), size/volume used, and number of applications.

Documentation Required
Surgical reconstruction documentation
For surgical reconstruction uses (e.g., skull base, mastoid lining), include detailed operative documentation demonstrating the role of AlloDerm or similar products and expected outcomes.
Document indication (e.g., CSF leak repair), graft size, placement technique (endoscopic/trans-nasal), adjuncts used (fibrin glue, packing), and postoperative follow-up demonstrating graft success.
Provide pre- and post-operative imaging or operative notes when available to support reconstructive use.

Documentation Required
Product identification and application details
Product identification and application details should be provided: name, processing (cryopreserved vs dehydrated), formulation, and application method influence coverage and coding.
State whether product is cryopreserved, aseptically processed, dehydrated, or viable cellular; list whether applied topically, injected, or implanted.
For products with multiple formulations (e.g., Grafix Core vs Grafix Prime; Cytal/MatriStem variants), specify the exact formulation and intended use.

Documentation Required
Document wound characteristics and prior SOC
Document wound characteristics and prior SOC explicitly when requesting coverage for products with limited evidence; many trials required SOC failure prior to enrollment.
Describe prior SOC measures and durations (e.g., 2-week SOC with offloading and moist wound care or 4-week compression trial for VLUs).
For wounds excluded from trials (e.g., tendon/muscle/bone exposure), provide additional rationale and evidence if requesting use in those settings.

Documentation Required
Application and product documentation
Application and product documentation: record how the product was prepared, dosed, and administered; manufacturers’ instructions (e.g., hydration, rehydration, fixation) should be followed and noted.
For injectable/flowable products and particulates (e.g., ClarixFlo, Corplex P), document dose (mg or cc), reconstitution method, and volume administered.
For sheet products, note whether applied wet or dry and how many square centimeters were used.

Documentation Required
Documentation for Artiss use
When Artiss fibrin sealant is used for skin graft attachment, include indication, graft size, formulation, and method of application in documentation for authorization or claims.
Document that Artiss is being used for skin graft attachment in burn patients (FDA-approved use), include graft size and whether pre-filled frozen or lyophilized form was used.
Record comparator fixation methods if relevant (e.g., staples) and expected benefit (reduced hematoma/seroma, improved adherence).

Documentation Required
Document product and size
Document product and size: authorization and claims should include the exact product name, size/volume used, and number of units to allow correct coding and payment.
For sheet-based allografts, state product size in cm2 and whether single-use kit components were used.
For implantable meshes and biologic plugs, include device size, configuration, and number implanted.

Documentation Required
Suggested documentation elements
Suggested documentation elements to include with prior authorization requests: device description, indication, wound dimensions, exposed structures, comorbidities, prior therapies, number of applications, and anticipated follow-up.
Include clinical photographs when available, baseline and interval wound measurements, and expected timeframe to reassess healing.
Supply cost/utilization estimates if relevant (number of grafts expected, approximate product cost) to inform case review.

Documentation Required
Dose and administration details
Dose and administration details: for particulate, injectable, or flowable products, provide dose (mg or cc), preparation steps, and route of administration.
ClarixFlo dosing is supplied as 25 mg, 50 mg, and 100 mg vials — document dose and preparation for injection or placement.
For flowable or particulate formulations, include reconstitution volume and technique and whether the product was injected or applied topically.

Documentation Required
Application and product size
Application and product size: for sheet products, state exact size and whether applied wet or dry; for injectable/packable products, indicate volume/cc used and number of units.
Record the surface area treated in cm2 and the number of sheets or units applied.
Document whether product was trimmed or customized and whether fixation (sutures, glue) was used.

Documentation Required
Product formulation and size documentation
Product formulation and size documentation: manufacturers supply multiple formulations and sizes; authorization requests must specify the formulation (sheet, tri-layer, injectable, powder) and size.
Examples: Biovance Tri-Layer (multiple sizes) vs single-layer Biovance — specify which was used.
For Cytal/MatriStem surgical matrix (implantable) versus wound sheet (topical), indicate the exact product line and size.

Step Therapy
Step therapy, alternatives, and preferred approach
Step therapy and alternatives: evidence and CPB guidance imply a stepwise approach where standard of care is attempted before advanced/allograft products; document alternatives tried and reasons for escalation.
SOC-first approach was used in many trials (2-week SOC screening) — prior authorization should confirm SOC trial and failure.
Preferred surgical approach: for abdominal wall repair, preferentially document attempts at primary fascial coaptation with mesh reinforcement rather than planned bridged repairs when feasible.

Step Therapy
Conservative care before biologic plug and comparative evidence guidance
Conservative care is often effective (e.g., non-operative management for fistulas closes many cases over 6–8 weeks); biologic plugs and advanced interventions should be reserved for failures of conservative care.
For enteric or anal fistulas, document a period of non-operative management (6–8 weeks) before considering biologic plug placement.
Comparative evidence may inform product selection: cite head-to-head or registry/claims analyses when available (e.g., MatriStem vs Dermagraft trials or claims-based comparisons).

Certain products (eg, AmnioBand, Apligraf) are indicated for difficult‑to‑heal venous ulcers when conservative compression therapy for ≥4 weeks has failed.

Documentation expectationDocument duration and failure of ≥4 weeks of conservative measures (eg, compression) when requesting advanced skin substitute coverage for venous ulcers.

Skin substitute / soft tissue substitute — definition

DefinitionBiologic, biosynthetic, or engineered products (eg, dermal matrices, amniotic membrane allografts, cultured skin equivalents) applied to wounds, burns, or surgical sites to replace or support damaged dermis or epidermis.

FormsAvailable as sheets, powders/micronized matrix, particulate/vial formats, injectable suspensions, or flowable preparations depending on product.

Intended roleAct as scaffold/barrier to support granulation, epithelialization, and tissue remodeling; processing and composition vary by product and affect indications.

Skin substitute — cellular or acellular matrices definition

DefinitionCellular or acellular matrices derived from human, nonhuman, synthetic, or composite materials used as scaffolds to support wound healing.

ExamplesIncludes acellular dermal matrices (human cadaveric), porcine urinary bladder matrix (UBM), and engineered cellular skin equivalents such as Apligraf.

Clinical noteProcessing (decellularization, sterilization) and whether cellular elements are retained determine regulatory status and clinical behavior.

ACM Surgical Collagen (sheet) — product definition

Product typeACM Surgical Collagen (sheet) is a 100% native freeze‑dried type‑1 bovine collagen matrix provided as sterile single‑use sheets intended as a scaffold for partial‑ and full‑thickness wound management after wound bed preparation.

PresentationSupplied in sterile single‑use pouches with multiple sheet sizes (eg, 2x2, 4x4, 5x4, 7x7, 8x12 inches).

Application noteApplied directly to prepared wound surface after removal of necrotic debris and biofilm; usually one matrix per application though repeats may be needed.

ACM Surgical Extra Advanced Collagen Powder — product definition

Product definitionACM Surgical Extra Advanced Collagen Powder is a sterile collagen powder formulation indicated for management of partial‑ and full‑thickness wounds, supplied in single‑use pouches/vials.

PresentationAvailable in 1 g pouches/vials and larger vial sizes for point‑of‑care application after wound bed preparation.

ApplicationApplied directly to prepared wound surface following removal of necrotic debris and biofilm.

ActiGraft — product definition

Product descriptionActiGraft is an FDA‑cleared regenerative wound care solution that produces in‑vitro blood clot tissue from a patient’s whole blood to serve as a biologic scaffold and protective covering.

Evidence noteA clinical trial for DFUs was listed as recruiting with estimated completion in 2022, but peer‑reviewed evidence supporting chronic DFU use is lacking.

Use implicationDocumented lack of published evidence for chronic DFU and other indications limits broad coverage until higher‑quality data are available.

ACM Surgical Extra / AC5 / Affinity — representative product examples

Representative examplesACM Surgical Extra (collagen powder), AC5 Advanced Wound System (self‑assembling peptide matrix), and Affinity (minimally processed amniotic membrane) are examples of collagen powder, peptide matrix kits, and amniotic membrane allografts respectively.

FormulationsExamples illustrate common formulations: powder, hydrated kit (self‑assembling peptides), and sheet‑based amniotic membranes supplied in single‑use formats.

Clinical applicationAll require wound bed preparation prior to application; manufacturers specify intended wound sizes or kit‑based application limits (eg, AC5 for wounds up to ~20–25 cm2).

AHD / acellular human dermis — definition and reported failure rate

DefinitionAHD (acellular human dermis) is biologic graft material derived from human dermis processed to remove cells and used as an acellular scaffold for tissue repair.

Reported failure rateReported aggregate failure rate approximately 13.6% at 12 months in hernia literature for some AHD cohorts.

Clinical implicationFailure rates and outcomes vary by material source, processing, and implant scenario; document product type and expected durability.

SIS / small intestinal submucosa — definition and reported failure rate

DefinitionSIS (small intestinal submucosa) is a porcine‑derived biologic graft used as an extracellular matrix scaffold in soft‑tissue repair and wound management.

Reported failure rateAggregate failure rate reported ~6.7% at 19 months in hernia literature for SIS in pooled analyses.

Usage noteOutcomes depend on material processing and clinical context; comparative evidence is limited and heterogenous.

Bridged repair — definition and clinical implications

DefinitionBridged repair: abdominal wall reconstruction using mesh to bridge fascial edges without primary fascial coaptation.

Clinical implicationsBridged repairs are associated with substantially higher hernia recurrence and complication rates compared with mesh‑reinforced primary fascial coaptation; bridged technique is an independent predictor of recurrence.

Coverage considerationWhen planning ADM/biologic mesh use, document whether primary fascial coaptation will be achieved; bridged repairs carry higher risk and may influence authorization decisions.

AlloGen — product definition

Product definitionAlloGen is a human liquid amnion product intended for treatment of non‑healing wounds and burn injuries; supplied in single‑use vials and dosed per cubic centimeter for external application.

PresentationSupplied in single‑use vials ranging from 0.25 to 2.0 mL; processed aseptically and terminally sterilized per manufacturer statements.

Intended useApplied externally as a biologic scaffold and protective covering for wound repair per manufacturer guidance.

AlloMax — product definition

Product definitionAlloMax is a dry sheet sterile human dermis allograft (epidermal and dermal layers removed/processed) used to repair abdominal wall wounds, hernia repairs, and reconstructive applications.

UsageOften used in multiple pieces sutured together for complex abdominal wall defects; intended to support cell in‑growth and revascularization when placed on well‑vascularized tissue.

Form sizesSupplied in a variety of sizes in sterile individual pouches; product attributes differ among similar ADM products.

AlloPatch Pliable (HR-ADM) — product definition

Product definitionAlloPatch Pliable (HR‑ADM) is a human reticular acellular dermal matrix processed aseptically to preserve an open, interconnected scaffold intended to facilitate fibroblast and endothelial cell infiltration and support wound healing in chronic DFUs.

Processing/structureAseptically processed reticular cut preserves collagens, elastin, glycosaminoglycans and hyaluronic acid to support cellular infiltration and angiogenesis.

Clinical evidence noteHR‑ADM has been evaluated in randomized trials comparing to standard of care showing improved short‑term healing rates in DFUs (see policy evidence summaries).

AlloSkin / AlloSkin RT — product definition

Product definitionAlloSkin / AlloSkin RT are meshed biologic cadaveric dermis allografts, low‑dose e‑beam irradiated, used as temporary skin replacements for partial or full‑thickness wounds; they typically slough in 7–14 days as granulation proceeds.

ApplicationSurgically applied and secured by sutures, staples, or adhesive; used for burns, trauma, chronic wounds (venous, arterial, neuropathic ulcers) when autograft not feasible.

Storage/presentationAlloSkin RT is shelf‑stable due to low‑dose e‑beam irradiation and does not require cryogenic storage; supplied in specified sizes (eg, 4x4 cm, 5x5 cm).

Alloskin AC / RT — product definition

Product definitionAlloskin AC / RT are human cadaveric dermal allografts processed (including decellularization and low‑dose e‑beam irradiation) and supplied in specified sizes as a scaffold for wound healing and temporary skin replacement.

IndicationsIntended for partial or full‑thickness wounds due to burns, trauma, or chronic wounds; applied and secured by the surgeon with usual fixation methods.

NoteProcessing and sterilization methods (eg, e‑beam) distinguish product variants and affect handling and storage requirements.

dHACA — definition

DefinitiondHACA (dehydrated human amnion and chorion allograft) is an aseptically processed dehydrated placental membrane allograft containing amnion and chorion intended as a scaffold and source of extracellular matrix proteins, cytokines, and growth factors for wound healing.

Clinical evidencedHACA (eg, AmnioBand) has randomized controlled trial evidence showing higher healing rates versus standard of care in DFUs and venous leg ulcers in some trials described in the policy.

Formulation noteSupplied dehydrated and aseptically processed; reported outcomes and costs vary by study and product handling/wastage rates.

DDHAM — definition

DefinitionDDHAM (decellularized dehydrated human amniotic membrane) is a dehydrated, decellularized amniotic membrane product derived from placental amnion providing extracellular matrix components and growth factors for wound repair.

Examples and evidence noteProducts such as AmnioAMP‑MP and Biovance are DDHAM variants; some lack robust peer‑reviewed evidence and are described as having limited published support.

Storage/presentationProvided in dehydrated sheet forms and packaged for single‑use in multiple sizes; intended for topical application after wound preparation.

Dehydrated amniotic membrane allograft (DAMA) — definition

DefinitionDehydrated amniotic membrane allograft (DAMA) is a processed, sterile, noncrosslinked dehydrated human amnion membrane composed of epithelial and stromal layers intended to act as a scaffold and supply growth factors/collagens to support wound repair.

Manufacturer claimsDAMA products (eg, AmnioExCel/BioDExCel variants) are intended for partial and full‑thickness wounds and may be provided in sheet or dual‑layer formats depending on vendor.

Evidence caveatSeveral DAMA products are noted to have limited peer‑reviewed evidence; coverage depends on product‑specific evidence and indications.

Cryopreserved/amniotic particulate allograft — definition

DefinitionCryopreserved/amniotic particulate allograft comprises morselized amniotic membrane and amniotic fluid components preserved by cryopreservation to retain structural collagen, growth factors and cells; supplied as injectable vials for topical or subcutaneous application.

PresentationAvailable in multiple vial sizes (eg, 0.25–3.0 cc) and intended for mixing/rehydration at point of care per manufacturer instructions.

Intended useUsed to fill soft tissue defects or augment wound beds; clinical evidence varies by product and formulation.

Apligraf (Graftskin) — product definition and FDA status

Product definition and FDA statusApligraf (Graftskin) is a bilayered living human skin equivalent composed of neonatal keratinocytes and fibroblasts in a bovine collagen dermal layer; it received FDA premarket approval (PMA) for venous leg ulcers (1998) and diabetic ulcers (2001).

IndicationsFDA‑approved for noninfected partial and full‑thickness skin ulcers due to venous insufficiency (>1 month) not responding to conventional therapy and for diabetic foot ulcers meeting labeled criteria.

Coverage implicationApligraf use should align with FDA labeling and documentation of failure of conservative therapy (eg, ≥4 weeks compression for venous ulcers) is expected.

Amniotic membrane-derived products — general definition

DefinitionAmniotic membrane‑derived products are derived from amnion, chorion, amniotic fluid, or umbilical tissues and may contain epithelial/stromal cells, matrix proteins, and growth factors; formulations and processing vary by manufacturer and affect biologic/mechanical properties.

Formulation variabilityProducts may be hydrated, dehydrated, decellularized, cryopreserved, or micronized; differences influence handling (stickiness), storage, and clinical application.

Evidence notePreclinical and early clinical data exist for many AM‑derived products but high‑quality human evidence is limited; clinical uses and indications depend on product specifics.

ArthroFlex (FlexGraft) — product definition

Product definitionArthroFlex (FlexGraft) is a decellularized human skin allograft containing collagen, elastin, growth factors, cytokines, and extracellular matrix intended for application to chronic wounds and explored for tendon/shoulder repair.

Formulation and sizesProvided in specific thicknesses and scaffold sizes (eg, 35x35 mm and 40x70 mm); manufacturer states additional sizes may be offered.

EvidencePeer‑reviewed literature primarily focuses on biomechanical properties and Level III–IV clinical evidence for orthopedic uses; robust randomized data are limited.

Artiss — product definition and intended use

Product definition and intended useArtiss is a slow‑setting fibrin sealant (human fibrinogen and low‑concentration thrombin) approved for attaching skin grafts in burn patients; sets in ~60 seconds to allow positioning before adhesion.

Regulatory contextFDA approved (March 2008) based on a phase III randomized trial demonstrating effectiveness in skin graft attachment for burns.

Clinical documentationDocument indication (skin grafting for burns), graft size, and outcomes (eg, wound closure assessments) when used as per trials and labeling.

Autologous PRP/APG/APC — definition

DefinitionAutologous platelet‑rich plasma (PRP)/APG/APC are concentrated growth‑factor preparations derived from the patient's own blood (platelet gel) used topically or as adjuncts to promote healing.

Evidence/regulatory noteCMS and guideline assessments (national non‑coverage determinations) have concluded insufficient evidence for platelet‑derived wound healing formulas for chronic non‑healing cutaneous wounds, influencing coverage decisions.

Clinical implicationPrior authorization and documentation of prior conservative therapy may be required; many payers consider these products investigational for chronic wounds.

Biobrane — product definition

Product definitionBiobrane is a biosynthetic wound dressing constructed of a silicon film with an embedded nylon fabric bound to collagen; used as a temporary cover to promote epithelialization and reduce pain/dressing changes in partial‑thickness burns.

Application constraintsVery deep wounds or wounds with high bacterial counts will not allow Biobrane adherence; joints must be splinted to prevent shear and failure of adherence.

Clinical advantagesWhen adherent, Biobrane can decrease hospital stay, pain, and frequency of dressing changes compared with some topical therapies in selected burn patients.

Amniotic allograft examples — product definition

ExamplesAmniotic allograft examples include AxoBioMembrane, Axolotl Graft/DualGraft, BioDfence, Biovance, and DermaBind SL — human placental/amnion‑derived products intended as wound coverings or scaffolds.

Formulations and sizesAvailable in hydrated or dehydrated forms, multiple sheet sizes (eg, 1.5x2 cm up to 15x15 cm) and particulate/vial formats depending on product.

Evidence variabilityLevel of clinical evidence varies widely across products; some lack peer‑reviewed studies while others have RCTs (eg, dHACA variants).

Bio-ConneKt — product definition

Product definitionBio‑ConneKt is an equine Type I collagen bioengineered skin substitute intended for management of moderately to heavily exuding wounds, including partial and full‑thickness and chronic ulcers.

SizesSupplied in multiple sizes (6x7 cm, 5x5 cm, 3x3 cm, 2x2 cm) and trimmed to fit wound margins prior to application.

ApplicationPlaced directly into the wound site and incorporated into the wound as healing proceeds; intended for topical use in exuding wounds.

DDHAM — definition and context

DDHAM contextDDHAM refers to dehydrated decellularized human amniotic membrane products (eg, AmnioAMP‑MP, Biovance) that provide a collagen‑rich extracellular matrix for tissue repair.

ProcessingDecellularization and dehydration aim to retain extracellular matrix proteins and growth factors while removing cellular components for storage and sterility.

Intended useApplied topically as sheets to partial/full‑thickness wounds after wound bed preparation; sizes and indications vary by product.

Hydrated vs dehydrated amniotic allograft — differences

Formulation differencesHydrated amniotic allografts are sticky and may not require adhesive; dehydrated forms are less sticky and may be preferable when instrumentation is used.

Clinical handlingHydrated products (eg, BioDfence) may adhere without glue; dehydrated (eg, BioDfence DryFlex) require rehydration or fixation depending on procedure.

Selection noteChoose hydrated vs dehydrated form based on wound location, need for instrumentation, and preferred fixation method; document selected form and rationale.

Celera Dual Membrane / Dual Layer — product definition

Product definitionCelera Dual Membrane / Dual Layer are minimally manipulated dehydrated human amniotic and/or chorionic membrane products, terminally sterilized and intended as wound covers or skin substitutes in sheets ranging from 1 to 49 cm2.

Dosage and sizingDosage is per cm2 and available sheet sizes total from 1 up to 49 cm2; stored at ambient temperature and packaged for single‑use.

Evidence notePolicy notes a lack of evidence regarding effectiveness for Celera Dual Membrane/Dual Layer products.

Conexa Reconstructive Matrix — product definition

Product definitionConexa Reconstructive Matrix is a porcine dermis tissue substitute processed to remove cells and sterilized, intended to reinforce soft tissue repairs (tendon repair, body wall defects) and supplied in sizes from ~2x4 cm to 5x10 cm.

Intended applicationsReinforcement of tendon repairs (rotator cuff, Achilles, patellar, biceps) and repair of body wall defects requiring reinforcement or bridging material.

Evidence caveatPolicy states insufficient evidence beyond case reports to support safety and effectiveness for some Conexa indications.

MatriStem/Cytal — product definition

Product definitionMatriStem/Cytal are porcine urinary bladder‑derived extracellular matrix products supplied as sheets or micronized powder intended for management of partial and full‑thickness wounds, pressure/venous/diabetic ulcers, tunneled/undermined wounds, surgical and trauma wounds.

Regulatory statusMatriStem Wound Sheet was cleared via FDA 510(k) (K112409) with indications for varied wound types; Micromatrix powder is supplied in mg vials for topical application.

Forms and dosingAvailable as wound sheets, microMatrix powder, surgical matrix variants and multiple sizes/weights for different wound scenarios.

Corplex / Corplex P — product definition

Product definitionCorplex (sheet) and Corplex P (particulate/vial) are human umbilical cord allografts derived from Wharton's jelly intended as wound coverings or packed grafts to supplement connective tissue voids.

Formats and sizesCorplex supplied in sheet sizes (eg, 2x2, 2x3, 3x5 cm) and Corplex P in vial fill volumes (1 cc, 2 cc, 4 cc) for topical packing; products are dehydrated and shelf stable up to 5 years when stored properly.

Evidence notePolicy states a lack of evidence regarding effectiveness for some Corplex variants.

UBM / urinary bladder matrix (Cytal/MatriStem) — product definition

DefinitionUBM (urinary bladder matrix; MatriStem/Cytal) is an acellular extracellular matrix derived from porcine urinary bladder tissue, non‑crosslinked, resorbable, and intended to support tissue regeneration when applied to wounds.

Clinical formsAvailable as sheets, micronized powder (MicroMatrix), and surgical matrix/implantable variants to manage diverse wound types.

MechanismProvides extracellular matrix scaffold that promotes regenerative remodeling and angiogenesis as it is resorbed and replaced by native tissue.

DermaBind SL — product definition

Product definitionDermaBind SL is a sterile, single‑use, dehydrated human amnion membrane allograft applied topically as a protective barrier for management of partial and full‑thickness wounds; fully resorbable.

IndicationsIntended for external application to wounds including pressure/venous/diabetic ulcers, surgical wounds, trauma wounds, and draining wounds; dosage per cm2 and reapplication possible.

HandlingApplied directly to prepared wound bed and adheres without fixation in many cases; packaged in various single‑use sizes.

DermACELL — product definition

Product definitionDermACELL is a decellularized human dermal allograft used as an extracellular matrix scaffold to support granulation and epithelialization in chronic non‑healing wounds and reconstructive applications.

Indications listedPolicy lists DermACELL for treatment of partial and full‑thickness neuropathic diabetic foot ulcers (>6 weeks) when used with standard diabetic ulcer care and for oro‑nasal fistula following cleft palate repair.

Product sizesSupplied in various sizes (eg, 4 to 96 cm2 and larger variants) and thickness ranges; limited published evidence exists for some indications.