CurrentUnitedHealthcarePolicy CS153KS.03

Skin and Soft Tissue Substitutes (for Kansas Only)

Medical policy governing medical necessity and coverage stance for skin and soft tissue substitute products for UnitedHealthcare Community Plan members in Kansas, including product-specific determinations and application limits.

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for Kansas Only)

Policy CodePolicy CS153KS.03

Change TypeNo material change

Effective DateNov 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and document trial of standard wound care (debridement, offloading/compression, adequate perfusion and infection-free status) before requesting advanced skin substitute use.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

1state this policy applies to

12wmax weekly application duration for EpiFix/Grafix

>=18member age group referenced

multipleproducts listed as unproven

67.9%DermACELL RCT healed rate vs SOC

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15RCTs in dermal matrix review

Coverage Criteria and Product-Specific Determinations

EpiFix / Grafix — Diabetic Foot Ulcer (Non-Injectable)

Covered when ALL of the following are met:

EpiFix/Grafix diabetic foot ulcer criteria: Adequate circulation to the affected extremity as indicated by one or more: pedal pulses palpable or pulses confirmed with Doppler OR ankle-brachial index (ABI) between 0.7 and 1.2; HgA1c < 12% within the last 90 days; ulcer has failed to demonstrate adequate healing after at least 4 weeks of standard wound care (including dressings to maintain a moist wound environment, debridement if present, and offloading); and no known contraindications such as active Charcot deformity or major structural foot abnormality, chronic infection at the ulcer site, known or suspected malignancy of the ulcer, or ulcer that extends to tendon, muscle, capsule, or bone.One application per week for up to 12 weeks

EpiFix and Grafix limited to one application per week for up to 12 weeks; use more frequently or beyond 12 weeks is considered unproven and not medically necessary.

TransCyte — Thermal Burns

Covered when ALL of the following are met:

TransCyte burn indication: TransCyte is indicated and medically necessary for treating surgically excised full-thickness thermal burn wounds and deep partial-thickness thermal burn wounds prior to autograft placement.

TransCyte is unproven and not medically necessary for other indications.

Chronic wound standard of care

Standard of care and step-up criteria for chronic wounds:

Standard Wound Care Requirements: Debridement of necrotic tissue as needed; maintain moisture balance with appropriate dressings; prevent and treat infection; correct ischemia when present; provide compression therapy for venous leg ulcers; and provide offloading for diabetic foot ulcers.

If 4 weeks of standard treatment do not produce a ≥50% reduction in wound size, consider change of or additional therapies (step-up to advanced biologics or other interventions).

Evidence-based coverage groupings

Coverage stance is determined by evidence availability for each listed product.

Insufficient evidence products: For each named product where the document states 'Studies are lacking' or 'There are few published studies addressing the use', it is not possible to conclude a beneficial effect on health outcomes; coverage decisions should reflect this limited evidence base.

Examples across these entries include multiple brand-specific amniotic/placental products and related allografts listed in the source chunks.

Affinity (HSAM): Affinity has limited published evidence including one multicenter RCT (Serena 2020) showing higher DFU closure rates versus standard care, but additional well-designed trials are needed to confirm findings.

Use may be considered only when clinical presentation matches trial populations and supporting documentation is provided.

Insufficient Evidence / Inconclusive Products

Products with insufficient or limited evidence — not enough to conclude clinical benefit:

Insufficient evidence group: Several named amniotic/placental products (for example: Amnio Quad-Core, Amnio Tri-Core, AmnioAmp-MP, Amnio Wound, AmnioWrap2, AmnioArmor, AmnioBind/DermaBind TL, AmnioCore, Amniocyte Plus, AmnioDefend FT Matrix, AMNIOEXCEL/BioDExcel and many others) have few published studies or insufficient evidence to determine a beneficial effect on health outcomes.

Use of these products should be supported by additional high-quality evidence before broad coverage is assumed.

dHACA (AmnioBand) — Evidence-supported product with limitations

AmnioBand (dHACA) evidence — summarized trial-based coverage considerations:

dHACA evidence summary: Multiple randomized trials and prospective studies of dehydrated human amnion/chorion allograft (AmnioBand/dHACA) reported higher healing rates and faster time-to-heal versus standard of care or versus other advanced dressings in selected DFU and VLU populations, but studies have limitations including lack of blinding, small sample sizes, and manufacturer involvement.

Positive trial examples and outcomes are summarized in key trial outcomes node.

Key trial outcomes: Representative findings include: DiDomenico et al. — 85% vs 33% healed at 12 weeks (dHACA vs SOC); Serena et al. — 75% vs 30% healed at 12 weeks (dHACA + SOC vs SOC); Glat et al. — 90% vs 40% healed at 12 weeks (dHACA vs TESS).

Results derive from small-to-moderate RCTs with noted methodological limitations.

Evidence-based stance by product

Evidence summaries for specific products and indications:

AMNIOEXCEL/AMNIOEXCEL Plus/BioDExcel: Evidence is insufficient or inconclusive due to study limitations; meta-analyses show trends toward increased healing but RCTs are small and at risk of bias.

ECRI and systematic reviews cited highlight limitations and call for larger trials.

AmnioFix (dHACM): Evidence is inconclusive for many wound indications; some small RCTs and observational studies suggest potential benefit in DFUs and other indications, but larger, well-controlled trials are needed.

ECRI and other reviews note limited follow-up and need for larger RCTs.

Other limited-evidence products: Several products (AMNIOMATRIX, Amnio-Maxx, AmnioPlast, Amniotext, Apis, Architect, etc.) have few published studies and insufficient data to conclude clinical benefit.

These product-specific summaries are evidence statements rather than definitive coverage criteria.

Product-specific evidence summaries

Product-specific evidence summaries (no definitive coverage determination stated in these excerpts):

Apis evidence summary: Few published studies exist for Apis; evidence insufficient to conclude clinical benefit.

Apis is a porcine gelatin–Manuka honey–hydroxyapatite product intended as an absorbable wound substitute.

Architect evidence summary: Few published studies exist for Architect; evidence insufficient to conclude clinical benefit.

Architect is an equine collagen ECM product; larger studies needed.

Biovance evidence summary: Biovance (DDHAM) registry data reported ~50% closure in heterogeneous chronic wounds over a median ~6.3 weeks, but evidence is from an observational registry and randomized trials are lacking; exclusions included actively infected wounds and known hypersensitivity.

Authors recommended validation in RCTs with standardized wound care.

Biovance (DDHAM) — registry evidence

Biovance (DDHAM) evidence summary:

Biovance registry findings: In a multicenter registry of heterogeneous chronic wounds (179 chronic wounds), nearly 50% achieved complete closure in a median of 6.3 weeks without product-related adverse experiences; registry exclusions included actively infected wounds and known hypersensitivity to DDHAM.

Authors recommend prospective randomized trials to validate findings given heterogeneity and observational design.

Insufficient evidence — multiple products

Multiple named amniotic/placental and related products — evidence insufficient:

Insufficient evidence: For the listed products (e.g., BioWound family, CaregraFT, CarePATCH, Celera products, Cellesta variants, ChoriPly, CLARIX variants, Cocoon, Cogenex, Coll-e-Derm, Complete family, Conexa, Corecyte, Coretext/Protext, etc.), there are few or no published studies and it is not possible to conclude a beneficial effect on health outcomes.

Coverage decisions should reflect this limited evidence base and may require prior authorization and clinical justification.

CorMatrix — ECM evidence and safety signals

CorMatrix (porcine SIS-ECM) evidence summary:

Insufficient evidence: Available evidence is insufficient to support CorMatrix; larger, robust studies are needed to establish safety and long-term outcomes.

Case series and small studies in cardiac applications have reported concerns including patch failure and reoperation in some series.

Observed adverse outcomes: Reports (e.g., Kelley et al.) documented recurrence of severe mitral regurgitation and reoperations related to ECM patch failure (e.g., 32% recurrence, 28% reoperation in one series), indicating potential product-specific safety signals in cardiovascular use.

These cardiac-specific findings do not directly translate to wound coverage but warrant caution for indications outside supported contexts.

DermACELL (D-ADM) — Covered with criteria

DermACELL products — evidence-supported coverage considerations:

DermACELL evidence-based criteria: DermACELL (D-ADM) has randomized controlled trial evidence and meta-analytic data showing higher healed proportions in DFUs versus standard care and improvements in percent wound area reduction; coverage may be considered when wound characteristics and prior conservative care match those studied.Refer to trial inclusion (chronic DFUs, neuropathic nonischemic, specified size/duration thresholds)

RCTs demonstrated increased healed ulcer rates (e.g., 67.9% vs 47.8% at 16 weeks) and greater percent area reduction; documentation should reflect trial-like selection and prior SOC failure.

Insufficient evidence / Not established

Products lacking adequate published evidence:

Insufficient evidence products: Corplex, Corplex P/Theracor P/Allacor P, Cryo-Cord, Cygnus variants, CYGNUS Disk, Cymetra, Cytal, DermaBind variants, Dermacyte products and others have few published studies and clinical benefit cannot be concluded.

These products may be considered investigational or not medically necessary until adequate evidence is available.

CorMatrix — cardiovascular applications (insufficient/concern)

CorMatrix — cardiovascular use concerns:

CorMatrix outcomes: Clinical reports and reviews indicate mixed and limited evidence for CorMatrix in cardiovascular reconstruction, including notable patch-failure and reoperation rates in some series; long-term safety and efficacy are not established.

Given these safety signals in cardiac use, CorMatrix is not supported for indications lacking robust evidence.

Products with limited or no evidence

Products with insufficient published evidence:

Insufficient evidence group: The listed products (including Derma-Gide beyond pilot data, DermaPure, DermaSpan, Dermavest, Derm-Maxx, Dual Layer Amnio Burgeon X-Membrane, DuoAmnion, EPIEFFECT, EpiFix Injectable, and many others) have few or no published studies; benefit on health outcomes cannot be concluded from current evidence.

These entries reflect limited evidence rather than explicit coverage denials; prior authorization and clinical justification may be required.

DermACELL — randomized trial evidence

Products with some randomized evidence:

DermACELL randomized evidence: DermACELL was evaluated in randomized trials (including a 16-week multicenter RCT) showing higher healed ulcer rates and greater percent wound area reduction versus conventional care in DFUs.

Trial designs allowed one or two applications; evidence supports consideration when patient/wound match trial characteristics.

EpiCord — randomized trial evidence

EpiCord randomized trial evidence and debridement effect:

EpiCord evidence: A multicenter randomized controlled trial showed higher 12-week complete closure rates for EpiCord versus alginate dressings in ITT and per-protocol analyses; ulcers receiving adequate debridement had markedly higher healing with EpiCord.

Trial included a 14-day run-in with standardized care and ulcer size 1–15 cm2; no device-related adverse events reported.

Derma-Gide — pilot observational evidence

Small observational/early studies:

Derma-Gide pilot: A 10-subject observational pilot of Derma-Gide reported 9 of 10 wounds healed within 4 weeks with mean time to heal 2.7 weeks; study limited by small size and lack of control group.

Larger randomized studies are needed to validate findings.

Study-based eligibility for use of dHACM/EpiFix in lower extremity diabetic ulcers

Criteria used in randomized trials for adjunctive use of EpiFix/dHACM (informative for coverage determination):

Main inclusion requirements: Ulcer size ≥ 1 cm2 and < 25 cm2; ulcer duration ≥ 4 weeks; unresponsive to standard wound care during a 2-week run-in (e.g., ≤25% closure or failure to improve); no clinical signs of infection; and adequate circulation demonstrated by TcPO2 ≥ 30 mm Hg OR ABI between 0.7 and 1.2 OR triphasic/biphasic Doppler arterial waveforms at the ankle.

These trial-based eligibility criteria inform typical clinical documentation and selection for adjunctive amniotic/placental products.

Study-based eligibility for use of EpiFix in venous leg ulcers

Criteria used in RCTs for adjunctive EpiFix with compression therapy:

VLU trial inclusion: Full-thickness non-healing venous leg ulcer refractory to optimized multilayer compression and moist dressings; treated with weekly EpiFix in addition to compression versus compression alone as randomized interventions.

Trial enrollment generally required prior compression therapy (minimum 14 days) and exclusion of infected or non-venous etiologies.

Evidence summaries (not explicit coverage criteria)

Summary of clinical evidence reported in this document segment:

EpiFix RCT outcomes: Randomized trials showed that weekly EpiFix plus compression or standard care in selected populations had higher complete healing rates versus compression or standard care alone (examples: 60% vs 35% at 12 weeks; 71% vs 44% at 16 weeks) and improved time-to-healing; however, trials were often manufacturer-sponsored and require confirmation in larger independent RCTs.

Smaller observational and retrospective series for Grafix and vCPM report favorable closure rates but comparative effectiveness remains uncertain.

Grafix evidence summary: Grafix (cryopreserved placental membrane, vCPM) RCTs and observational studies suggest efficacy in DFUs and VLUs refractory to standard care (e.g., Lavery RCT: 62% vs 21% closure at 12 weeks); registry and retrospective analyses report closure rates ~59% with median treatment durations of ~42 days in selected cohorts.

Evidence quality varies and additional independent trials are desirable.

Coverage-aligned clinical criteria

Coverage more likely supported when patient and wound characteristics match those enrolled in the positive trials:

Core inclusion-like criteria: Chronic diabetic foot ulcer or venous leg ulcer consistent with trial populations; documented wound size and duration per trials; adequate tissue perfusion (ABI/TcPO2/Doppler) and absence of active infection; and failure of an optimized trial of standard wound care prior to adjunctive allograft use.As per trial criteria (e.g., ulcer ≥1 cm2 and <25 cm2; duration ≥4 weeks; run-in nonresponse)

Documentation should mirror trial entry criteria to align coverage rationale with evidence.

Product-specific evidence notes: Grafix demonstrated higher closure rates vs SOC in an RCT and supportive registry data; other products have limited or inconclusive evidence and require case-by-case justification.N/A

See individual product summaries for trial details.

Coverage stance summaries by product group

Summaries indicate whether available evidence supports effectiveness and safety for each named product:

Products with inconclusive evidence: Integra Flowable Wound Matrix, InteguPly, Interfyl, Keramatrix, Kerecis Omega3 products, MatriDerm, and many others have studies with limitations (small size, nonrandomized designs); available evidence is insufficient to draw definitive conclusions regarding effectiveness across broad clinical use.

Some products show promising early data but require larger, higher-quality RCTs for definitive coverage decisions.

Kerecis and fish skin grafts: Kerecis fish skin grafts have evolving evidence including some RCTs and case series showing promising results for DFUs and burns, but overall evidence remains limited and additional trials are ongoing or needed.

Evolving evidence reviews (Hayes/ECRI) indicate inconclusive evidence pending larger trials.

General 'Not enough evidence to conclude benefit' criteria

Summary coverage stance for the products in this section:

Evidence summary: For the majority of listed products (e.g., MatriDerm, Matrion, MatriStem MicroMatrix, Mirragen, Myriad Morcells, and numerous others), available studies are few, low-quality, or lacking; it is not possible to conclude these products have a beneficial effect on health outcomes based on current evidence.

These products should generally be considered investigational or require strong clinical justification and prior authorization for use.

Limited positive evidence (Mirragen)

Exception where limited RCT evidence exists:

Mirragen BBGFM RCT findings: A small RCT (Armstrong et al. 2022) reported improved healing rates and percent area reduction in Wagner 1 DFUs when Mirragen BBGFM was added to standard of care versus standard of care alone at 12 weeks; study limitations and small sample size limit conclusiveness and require confirmation in larger trials.

Positive results are suggestive but not definitive for broad coverage.

The policy identifies a long list of named skin and soft tissue substitute products as unproven and not medically necessary for any indication due to insufficient evidence of efficacy. Examples include, but are not limited to, Abiomend (Membrane/Hydromembrane/Xplus variants), ACApatch, Acesso family (Acesso, Acesso AC, Acesso DL, Acesso TL), Activate Matrix, AdvoGraft Dual and One, AeroGuard and NeoGuard, Amnio-family products (e.g., AmnioQuad-Core, Amnio Tri‑Core, AmnioArmor, AmnioBand), AMNIOEXCEL/BioDExcel, AmnioFix, Apis, Architect, ArdeoGraft, Biovance variants, many BioWound and Cellesta products, CorMatrix/Corplex family, Dermacyte/Derma-Gide/DermaPure, DermACELL entries, Grafix Core/Plus, Hyalomatrix, Integra Flowable Wound Matrix, Kerecis Omega3 products, MatriDerm, Matrion, Mirragen, Myriad family, NeoPatch/NeoX products, NovoSorb SynPath, PermeaDerm products, Phoenix/Restrata/Restorigin families, and numerous others listed in the policy.

Because these products are characterized in the policy as having few or no published studies, small or single-arm series, or otherwise insufficient high-quality evidence, their routine use is described as unsupported by conclusive data and may be considered not medically necessary until adequate evidence demonstrating clinical benefit is available.

Listing of a procedure or HCPCS code in this policy is provided for reference only and does not imply that the service described by the code is a covered or non-covered health service. Benefit coverage and reimbursement are determined by applicable federal, state, or contractual requirements and laws; inclusion of a code here does not guarantee coverage or payment.

For many brand-specific amniotic, placental, and related products, the document summarizes that there are few published studies or that existing studies are limited. Examples called out include AMNIOEXCEL / BioDExcel (and AMNIOEXCEL Plus), AmnioFix, AMNIOMATRIX / BioDMatrix, Amnio‑Maxx variants, AmnioPlast products, AmnioRepair/AltiPly, Amniotext and Amniotext Patch, Amnion Bio, AMNIPLY, Apis, Architect, and several other single‑product entries where evidence is sparse or inconclusive.

These product summaries note that while small studies or early reports may exist for some items, limitations (small sample sizes, single-arm design, risk of bias) prevent concluding a clear beneficial effect on health outcomes and indicate the need for larger, well‑designed trials to establish efficacy and safety.

Within the cited sections, the document does not list explicit policy exclusions beyond the repeated statement that evidence is lacking for many products. In other words, the entries predominantly describe an insufficient evidence stance rather than enumerating formal coverage exclusions for specific clinical scenarios.

Procedure, HCPCS and Related Codes

Applicable A-codes (selected)HCPCS

A2001	InnovaMatrix AC, per sq cm.
A2002	Mirragen Advanced Wound Matrix, per sq cm.
A2004	XCelliStem, 1mg.
A2005	Microlyte Matrix, per sq cm.
A2006	NovoSorb SynPath dermal matrix, per sq cm.
A2007	Restrata, per sq cm.
A2008	TheraGenesis, per sq cm.
A2009	Symphony, per sq cm.
A2010	Apis, per sq cm.
A2011	Supra SDRM, per sq cm.

1–10 of 25

1/3

Applicable Q- and A-codes (selected)HCPCS

A2032	Myriad Matrix, per sq cm.
A2033	Myriad Morcells, 4 mg.
A2034	Foundation DRS Solo, per sq cm.
A2035	Corplex P or Theracor P or Allacor P, per mg.
A4100	Skin substitute, FDA-cleared as a device, not otherwise specified.
Q4100	Skin substitute, not otherwise specified.
Q4110	PriMatrix, per sq cm.
Q4111	GammaGraft, per sq cm.
Q4112	Cymetra, injectable, 1 cc.
Q4114	Integra flowable wound matrix, injectable, 1 cc.

1–10 of 20

1/2

Referenced A-codes and HCPCS device codes (partial list shown)HCPCS

A2001	InnovaMatrix AC, per sq cm
A2002	Mirragen Advanced Wound Matrix, per sq cm
A2004	XCelliStem, 1mg
A2005	Microlyte Matrix, per sq cm
A2006	NovoSorb SynPath dermal matrix, per sq cm
A2007	Restrata, per sq cm
A2008	TheraGenesis, per sq cm
A2009	Symphony, per sq cm
A2010	Apis, per sq cm
A2011	Supra SDRM, per sq cm

1–10 of 25

1/3

Referenced Q-codes and additional HCPCS (partial list shown)HCPCS

A2032	Myriad Matrix, per sq cm
A2033	Myriad Morcells, 4 mg
A2034	Foundation DRS Solo, per sq cm
A2035	Corplex P or Theracor P or Allacor P, per mg
A4100	Skin substitute, FDA-cleared as a device, not otherwise specified
Q4100	Skin substitute, not otherwise specified
Q4110	PriMatrix, per sq cm
Q4111	GammaGraft, per sq cm
Q4112	Cymetra, injectable, 1 cc
Q4114	Integra flowable wound matrix, injectable, 1 cc

1–10 of 128

1/13

Product mentions (no billing codes listed in this section)mixed

No codes listed

No billing or procedure codes present in these chunksmixed

No codes listed

inv-69: HgA1c — < 12% (within the last 90 days) — supportive clinical threshold

HgA1c threshold< 12% within the last 90 days

Clinical relevanceRequires HgA1c < 12% as part of EpiFix/Grafix DFU eligibility

Documentation windowResult must be from within the prior 90 days

inv-70: Ankle-Brachial Index (ABI) — Between 0.7 and 1.2 — supportive clinical threshold

ABI threshold (DFU/DFU trials)ABI between 0.7 and 1.2

Prior Authorization, Documentation and Step Therapy Guidance

Prior Authorization

Prior authorization for skin substitutes

Prior authorization may be required for the use of skin and soft tissue substitutes (including placental/amnion-derived products, acellular dermal matrices, and other advanced biologic/allograft wound products) because study designs and the evidence base vary widely across products. Inclusion of a product or code in the policy does not guarantee coverage; providers should obtain prior authorization when the product has limited, heterogeneous, or product-specific evidence.

Prior authorization requests should reference the specific product, indication, and supporting clinical documentation.
Listing of HCPCS/A-codes in the policy is for reference only and does not imply coverage — verify benefit coverage prior to ordering.

Documentation Required

Clinical entry criteria commonly required

Clinical entry criteria frequently used in trials and that may be expected in authorization reviews include measures of adequate perfusion (e.g., ABI, TcPO2, SPP, Doppler waveforms), limits on wound size and duration, and demonstration of an inadequate response to a standardized run-in period of standard of care (SOC). Many RCTs required no clinical signs of infection and laboratory limits (e.g., HgA1c, serum creatinine) within defined windows.

Background and Evidence Overview

Full‑thickness (third‑degree) thermal burns involve destruction of all layers of the skin, including epidermis and dermis, with variable subcutaneous involvement; partial‑thickness (second‑degree) thermal burns involve the epidermis and part of the dermis, with deep partial‑thickness burns affecting most of the dermis and leaving fewer intact appendages and nerve endings. TransCyte is identified in the policy as indicated for use on surgically excised full‑thickness thermal burns and deep partial‑thickness thermal burns prior to autograft, consistent with the clinical definitions and InterQual references cited for members age ≥18.

Definitions and Product Descriptions

inv-145: Full-Thickness Thermal Burn (Third Degree Burn)

DefinitionFull-thickness (third-degree) thermal burn: destruction of all layers of the skin involving epidermal and dermal layers with variable subcutaneous involvement

Clinical implicationIndicates deepest burns where TransCyte may be considered prior to autograft in policy context

Source referenceGomez and Cancio, 2007 definition provided in policy definitions section

inv-146: Partial-Thickness Thermal Burn (Second Degree Burn)

DefinitionPartial-thickness (second-degree) thermal burn: involves epidermis and part of dermis; deep partial-thickness involves most of the dermis

Clinical implication

Revision History

2025-11-01policy_revisionLatest

Policy updated effective 2025-11-01: coverage rationale revised for members 18+, list of products designated unproven/not medically necessary was updated (added AmnioPlast 3; removed several items) and codes Q4368–Q4382 added; clinical evidence and references updated.

Page 10 of 91 Effective 11/01/2025document_pagination

Document pagination indicates Effective 11/01/2025 on page 10 of 91.

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for Kansas Only)

Policy CodePolicy CS153KS.03

Change TypeNo material change

Effective DateNov 1, 2025

Next Review DateN/A

SourceLink

On This Page

As evidence of adequate perfusion

ABI 0.7–1.2 acceptable to demonstrate circulation to the affected extremity

Alternative perfusion measures citedTriphasic/biphasic Doppler waveforms at the ankle (trial protocols referenced)

inv-71: Application frequency/duration — One application per week for up to 12 weeks

Maximum application frequency/durationOne application per week for up to 12 weeks

Products referencedLimit applies to both EpiFix and Grafix (non‑injectable forms)

Use beyond limitsApplications more frequently than once weekly or beyond 12 weeks are considered unproven/not medically necessary

inv-72: Vascular perfusion thresholds — ABI > 0.75 OR SPP > 30 mmHg OR TCOM > 30 mmHg

Primary perfusion thresholdsABI > 0.75 OR SPP > 30 mmHg OR TCOM (TcPO2) > 30 mmHg

Context of useEntry criteria used in multiple trials to confirm adequate limb perfusion prior to graft application

Alternate trial perfusion criteriaTcPO2 ≥ 30 mm Hg or triphasic/biphasic Doppler waveforms also cited in protocols

inv-73: Venous leg ulcer wound area — ≤ 2 cm² but < 20 cm²

VLU wound area limits (trial)≤ 2 cm² but < 20 cm²

Ulcer characteristicsFull-thickness VLU not extending to muscle/tendon/bone; treated with compression for ≥14 days prior to randomization

Duration requirement in trialVLU duration longer than one month per inclusion criteria

inv-74: Diabetic foot ulcer trials wound screening — Two-week SOC screening period prior to randomization

SOC screening period before randomizationTwo-week standard-of-care (SOC) screening/run-in prior to randomization

PurposeIdentify nonresponders (e.g., ≤25% closure) for trial eligibility

Typical SOC measuresDebridement, moist dressings (eg, collagen-alginate), offloading or compression during run-in

inv-75: Baseline wound area — average 3.1 cm2

Reported baseline wound area (registry)Average baseline wound area 3.1 cm² in Biovance registry chronic wounds

Study populationRegistry included heterogeneous chronic wounds (179 chronic wounds analyzed)

Median time to closure in registryMedian 6.3 weeks to closure reported

inv-76: Run-in wound area reduction threshold — ≤ 30% wound area reduction during a 14-day run-in (eligibility criterion in EpiCord trial)

Run-in wound area reduction eligibility threshold≤ 30% wound area reduction during a 14-day run-in (EpiCord trial)

Run-in purposeSelect nonresponders to standardized care for randomization to study treatments

Run-in interventionsWeekly debridement and moist wound therapy during 14-day run-in

inv-77: Ulcer size for EpiCord trial — 1 to 15 cm2 (inclusion criterion)

EpiCord inclusion ulcer size1 to 15 cm² (ulcer located below the ankle)

Ulcer depthFull-thickness ulcers not extending to muscle, tendon, or bone were included

Run-in and randomization14-day run-in with standardized care before randomization

inv-78: Ulcer size — ≥1 cm2 and <25 cm2

General ulcer size range used in trials≥ 1 cm² and < 25 cm²

Typical depth/disease restrictionsFull-thickness ulcers that do not probe to tendon/muscle/capsule/bone

Used for DFU RCT eligibilityCriteria appear in multiple DFU randomized trials (e.g., Zelen et al.)

inv-79: Ulcer duration — ≥4 weeks

Ulcer duration requirementDuration ≥ 4 weeks (chronic DFU inclusion)

Run-in screeningWounds entered a run-in and had to be unresponsive to standard care to qualify

ContextApplied across multiple DFU and VLU trial protocols

inv-80: TcPO2 — ≥30 mm Hg

TcPO2 thresholdTcPO2 ≥ 30 mm Hg (used to document adequate perfusion)

Role in eligibilityAlternative objective perfusion assessment when ABI/TcPO2 used in trial protocols

DocumentationReferenced as a requirement in several RCT inclusion criteria for DFUs

inv-81: ABI — 0.7–1.2

ABI range reiteratedABI 0.7–1.2 cited as trial and policy threshold for adequate circulation

Used for EpiFix/Grafix eligibilityABI between 0.7 and 1.2 accepted as evidence of adequate perfusion

Alternative documentationPedal pulses palpable or Doppler-confirmed pulses may substitute for ABI

inv-82: HgA1c — <12% (within 60 days)

HgA1c timing and threshold (trial)HgA1c < 12% within 60 days (trial-specified window)

Clinical implicationMultiple trials required relatively recent glycemic control documentation prior to enrollment

Comparison to policyPolicy for EpiFix/Grafix uses <12% within 90 days; some trials used 60-day window

inv-83: Serum creatinine — <3.0 mg/dL (within last 6 months)

Serum creatinine thresholdSerum creatinine < 3.0 mg/dL (within last 6 months)

Trial usageUsed as an exclusion/eligibility lab in DFU trials to limit enrollment of those with severe renal dysfunction

Documentation windowMeasured within prior 6 months per trial protocols cited

Common perfusion thresholds: ABI 0.7–1.2 or >0.75; TcPO2 or dorsum transcutaneous oxygen ≥ 30 mmHg; SPP > 30 mmHg; triphasic/biphasic Doppler waveforms at the ankle.
Typical wound size inclusion: most trials used 0.5–25 cm2 (many used 1–25 cm2); duration commonly >4 weeks and <52 weeks.
Run-in SOC screening commonly required: 1–4 week standardized wound care with debridement, moist dressings, offloading/compression and ≤25–30% wound area reduction to qualify for randomization.

Prior Authorization

Clinical eligibility may guide authorization

Authorization decisions may be guided by trial eligibility elements when they align with the member’s clinical status. Expected elements that can support medical necessity include documented adequate perfusion, absence of active infection, prior SOC trial with documented inadequate response, and relevant labs (e.g., HgA1c, serum creatinine) within specified timeframes.

Documented measures of perfusion (ABI, TcPO2, SPP, Doppler) and timing of tests.
Proof of a prior SOC trial and objective wound measurements showing insufficient healing (for example <50% reduction after 4 weeks or ≤25–30% reduction during run-in periods used in trials).
Recent labs: HgA1c within 60–90 days, serum creatinine within prior 3–6 months as applicable.

Prior Authorization

Prior authorization likely for products with limited evidence

Many named products in this policy have limited or inconclusive published evidence. Prior authorization is likely required for products with few, low-quality, or heterogeneous studies to allow clinical review and documentation of medical necessity.

Products with sparse evidence (multiple examples listed in policy) typically require submission of clinical rationale and supporting literature when requested.
When evidence is insufficient, payers may require additional justification or deny coverage as not medically necessary.

Documentation Required

Clinical documentation typically required before advanced allograft use

Clinical documentation typically required before approving advanced allograft or biologic skin substitutes includes wound characteristics (size, depth, duration), prior and current standard of care measures, objective perfusion assessments, infection status, relevant laboratory values, and prior use of cellular/tissue-based products.

Wound documentation: measured area in cm2, anatomical location, duration, description of depth and whether tendon/muscle/bone is involved.
Prior SOC: dates and descriptions of debridement, dressings, offloading/compression, and response (percent area reduction over the SOC period).
Perfusion and infection status: ABI/TcPO2/SPP/Doppler results, signs/symptoms of infection, and cultures if performed.
Relevant labs: HgA1c (within 60–90 days), serum creatinine (within last 3–6 months).

Prior Authorization

Prior authorization expectations

Authorization requests should align with treatment regimens and application frequency/duration demonstrated in trials. Requests for more frequent applications or durations beyond trial-based limits should include compelling rationale and supporting evidence.

Example limits from trials: many products applied weekly for up to 12 weeks (e.g., EpiFix, Grafix).
Provide documentation of the proposed number of applications and planned follow-up consistent with clinical trial protocols when available.
If requesting deviation from trial regimens (frequency or total duration), include clinical justification and supporting literature.

Prior Authorization

Prior authorization likely required for many listed products

Given the breadth of products reviewed and frequent evidence gaps, prior authorization is likely required for many listed skin substitute products. Requests should include product-specific evidence and patient-specific clinical justification.

Numerous products with limited published data are listed in the policy — expect additional review or requirements for medical necessity documentation.
In some cases, lack of evidence may result in denial or request for more information prior to approval.

Denial Risk

Evidence uncertainty may trigger coverage denial

Uncertainty or low quality of evidence for clinical benefit may trigger coverage denials. When comparative high-quality studies are lacking, or when study applicability to the requested patient is limited, requests may be declined as not medically necessary.

Denial risks increase when the request lacks documentation of prior SOC, objective perfusion data, or when the product’s evidence base is limited.
Products explicitly designated as unproven/not medically necessary in the policy are likely to be denied for all indications.

Denial Risk

Insufficient evidence triggers potential denial

Insufficient or inconclusive evidence for a specific product or indication may result in a determination of not medically necessary. Providers should document clinical rationale and cite available supportive studies when requesting coverage for products with limited evidence.

If a product is listed in the policy as unproven/not medically necessary, include strong clinical justification and peer-reviewed evidence if requesting exception.
Documentation should explicitly address gaps in evidence and why the product is clinically appropriate for the member.

Denial Risk

Population exclusions may affect coverage

Population exclusions used in trials or registries may affect coverage decisions. Examples include exclusion of actively infected wounds, ulcers previously treated with cellular/tissue-based products, pregnancy, or significant comorbidities.

Registry/trial exclusions often excluded actively infected wounds and known hypersensitivity to the product.
Authorization reviewers may apply similar clinical exclusions when determining medical necessity.

Denial Risk

Eligibility-based denials

When trial eligibility criteria are not met (for example inadequate perfusion, active infection, or recent significant wound improvement during run-in), authorization may be denied. Providers should document how the patient meets trial-like eligibility or provide rationale for differences.

Common exclusion reasons: active infection at the wound site, inadequate tissue perfusion, ulcer probing to tendon/muscle/bone, or recent improvement during SOC run-in.
If enrollment prerequisites cannot be met, include alternative clinical data and justification for why product use remains appropriate.

Documentation Required

Exclusions observed in registry

The Biovance registry and other observational studies used specific exclusions in real-world use (e.g., actively infected wounds, known hypersensitivity). Such exclusions inform expected documentation and may guide denial decisions when present.

Registries commonly excluded actively infected wounds and hypersensitivity to the product.
Reviewers may request evidence that these exclusions do not apply to the patient before authorizing product use.

Denial Risk

Limited evidence may trigger additional review or denial

Limited evidence for many products may prompt additional review steps such as requests for peer-reviewed literature, prior authorization justification, or denial. Providers should anticipate these requests and submit complete supporting documentation.

Expect requests for published studies, prior treatment history, and objective wound measurements when evidence is limited.
When available, include randomized controlled trials or systematic review citations that support the requested use.

Documentation Required

Trial-based clinical eligibility that may be expected

Trial-based clinical eligibility commonly required in RCTs and that authorizations may mirror include: adequate tissue perfusion (ABI/TcPO2/SPP/Doppler), absence of clinical infection, wound size and depth limits, and failure to respond to a standardized SOC run-in (e.g., ≤25–30% reduction during run-in).

Run-in periods: 1–4 weeks of standardized SOC with debridement, moist dressings, offloading/compression; many trials randomized only those with insufficient wound reduction during run-in.
Wound criteria: full-thickness wounds not extending to tendon/muscle/bone in many trials; common size ranges 1–25 cm2.
Perfusion and labs: ABI 0.7–1.2 or ABI >0.75, TcPO2 ≥30 mmHg, HbA1c <12% in many studies.

Denial Risk

Evidence limitations may prompt denials

Evidence limitations (small sample sizes, single-center trials, lack of blinding, heterogeneous products) have led to conservative coverage approaches. When evidence is limited, authorizations may be denied or require more stringent documentation of medical necessity.

Provide controlled-trial data and objective wound outcomes where available to support requests.
Acknowledgement of product-specific evidence limitations in the request can prompt additional review rather than immediate denial, but substantial gaps may still preclude coverage.

Documentation Required

Enrollment prerequisites in trials

Enrollment prerequisites used in trials (to support efficacy claims) that may be requested for authorization include: documented run-in SOC response, perfusion testing results, absence of infection, limits on ulcer depth, and relevant labs within protocol windows.

Document run-in SOC dates and wound percent reduction during run-in.
Include perfusion testing (ABI/TcPO2/SPP/Doppler waveform) and confirm absence of clinical infection.
Provide lab results (e.g., HbA1c, serum creatinine) within the timeframes used in trials when available.

Documentation Required

Evidence documentation and supporting clinical measurements

For products supported by trial evidence (for example DermACELL, EpiFix, Grafix), include trial-relevant documentation: wound size/duration, prior SOC details, perfusion measures, number and frequency of prior applications, and outcomes when applicable. Document expected number of applications consistent with trials (e.g., weekly applications up to trial limits).

DermACELL: document wound characteristics, prior SOC, and whether single or repeat application is being requested consistent with RCT protocols.
EpiFix/Grafix: document adequate circulation (pedal pulses or ABI 0.7–1.2 or TcPO2 ≥30 mmHg), HgA1c and other relevant labs within trial-specified windows, and prior SOC failure for the specified run-in period.

Step Therapy

Standard of care and step-up timeline

Standard of care must be documented prior to authorization for advanced products. SOC includes debridement, moist dressings, infection control, correction of ischemia, and compression (for VLUs) or offloading (for DFUs). Demonstrate inadequate response to SOC (e.g., <50% reduction at 4 weeks or failure during run-in periods) before requesting advanced biologics.

Describe debridement dates, dressing types, offloading/compression interventions, and objective percent area change during the SOC trial.
Many trials required at least 1–4 weeks of SOC or a 14-day run-in with standardized care; document this period in the request.

Step Therapy

Step therapy and adjunctive use after inadequate response to standard care

Adjunctive use of advanced allografts is generally considered after inadequate response to a documented SOC run-in. For DermACELL and similar products with some RCT support, step-therapy expectations include documentation of prior SOC and justification for the selected advanced product.

For DermACELL, requests should document prior SOC, wound measurements, and whether the request is for single or multiple applications as used in trials.
When comparative evidence exists (e.g., vCPM vs other advanced products), include such data if relevant to the clinical justification.

Deep partial-thickness wounds may be appropriate for TransCyte prior to autograft as noted in policy

Source referenceGomez and Cancio, 2007 definition provided in policy definitions section

inv-147: Skin substitutes — definition

DefinitionSkin substitutes: biologic, synthetic, or biosynthetic materials that provide temporary or permanent wound coverage and mimic skin properties to promote healing

Classification factorsClassified by cellularity, layering, replaced region, materials used, and permanence

Common typeMost commercially available products are acellular dermal substitutes (eg, decellularized human dermis or placental membranes)

inv-148: Kumar classification — classification example

Kumar classification exampleClass 1: temporary dressings; Class 2: single-layer durable substitutes (epidermal or dermal); Class 3: composite skin substitutes including bioengineered skin/grafts

UseProvides a common framework referenced in the policy for categorizing products

SourceKumar 2008 updated 2023 referenced in policy definitions

inv-149: Acellular dermal substitutes — definition

DefinitionAcellular dermal substitutes: products processed to remove cellular components (eg, from human placental membranes or animal tissue) providing a matrix to support healing

Common sourcesDecellularized donated human dermis, human placental membranes, and animal tissue-derived matrices

Clinical roleProvide scaffold for cell migration and tissue regeneration in chronic wound management

inv-150: Cellular dermal substitutes — definition

DefinitionCellular dermal substitutes: products that contain viable or nonviable cellular components intended to augment healing beyond an acellular matrix

Evidence noteSome cellular products have randomized evidence (eg, DermACELL) while many have limited studies

Clinical implicationMay provide additional biologic activity compared with acellular matrices in certain trials

inv-151: AdvoGraft Dual — product description

Product descriptionAdvoGraft Dual: dual-layer amniotic membrane derived from processed human placental tissue used as a barrier and cover for acute and chronic wounds

Evidence statusStudies are lacking; evidence insufficient to conclude clinical benefit

Intended useBarrier and wound cover applications in acute and chronic wounds

inv-152: AdvoGraft One — product description

Product descriptionAdvoGraft One: single-layer amniotic membrane used as a barrier and cover for acute and chronic wounds

Evidence statusStudies are lacking; insufficient evidence to conclude benefit

Intended useProtective wound covering for acute and chronic wounds

inv-153: AeroGuard — product description

Product descriptionAeroGuard: dehydrated single-layer human amniotic membrane allograft intended as a protective wound covering for acute and chronic wounds

Evidence statusStudies are lacking; clinical benefit not established

Manufacturer noteDerived from donated human birth tissue for homologous wound covering use

inv-154: NeoGuard — product description

Product descriptionNeoGuard: dehydrated double-layer human amniotic membrane allograft intended as a protective wound covering for acute and chronic wounds

Evidence statusStudies are lacking; insufficient evidence to conclude benefit

Intended useHomologous wound covering derived from donated human birth tissue

inv-155: Affinity — product description and RCT reference

Product descriptionAffinity (HSAM): a human skin-derived amniotic membrane fluid allograft intended for wound repair and healing

RCT evidenceOne multicenter RCT (Serena 2020) reported higher DFU closure rates with Affinity + SOC vs SOC alone but was small and had limitations

Evidence implicationPromising but requires larger trials for confirmation

inv-156: Amnio Quad-Core — product description

Product descriptionAmnio Quad-Core: four-layer allogeneic amniotic membrane allograft used as a single-use barrier covering

Evidence statusStudies are lacking; insufficient evidence to conclude benefit

Manufacturer detailsProcessed human tissue screened per regulatory standards

inv-157: Amnio Tri-Core — product description

Product descriptionAmnio Tri-Core: three-layer allogeneic amniotic membrane allograft used as a covering

Evidence statusFew published studies; clinical benefit not established

Intended useBarrier covering for acute and chronic wounds

inv-158: AmnioBand / dHACA — product description

Product descriptionAmnioBand / dHACA: dehydrated human amnion and chorion allograft (marketed as AmnioBand/Guardian) used as adjunct to standard of care for DFUs and VLUs

RCT outcomesMultiple RCTs reported higher healing rates vs SOC or Apligraf in selected DFU/VLU populations (eg, DiDomenico, Glat, Serena, DiDomenico multi-site series)

Evidence limitationsTrials limited by small sizes, lack of blinding, and manufacturer involvement; findings need independent confirmation

inv-159: AmnioAmp-MP — product description

Product descriptionAmnioAmp-MP: sterile human tissue allograft membrane patch intended for acute and chronic wounds and to enhance soft tissue healing

Evidence statusFew published studies; insufficient evidence to conclude benefit

Intended applicationsSurgical soft tissue healing, scar reduction, and wound coverage

inv-160: AMNIOEXCEL / BioDExcel — product description

Product descriptionAMNIOEXCEL / BioDExcel: dehydrated human amnion-derived tissue allograft with intact ECM for soft tissue repair and reconstruction

Evidence statusInsufficient/inconclusive evidence; larger studies needed (ECRI assessment)

Product variantsAMNIOEXCEL Plus incorporates additional layers of amnion/chorion

inv-161: AMNIOEXCEL / BioDExcel / AMNIOEXCEL Plus — product description

Product familyAMNIOEXCEL / BioDExcel / AMNIOEXCEL Plus: dehydrated amnion-derived allografts intended to advance soft tissue repair

Evidence noteEfficacy inconclusive due to study limitations and high risk of bias in available studies

Use contextIntended for wound and soft tissue reconstruction applications

inv-162: AmnioFix — product description

Product descriptionAmnioFix: composite amniotic tissue membrane available in sheet/membrane, particulate, and wrap configurations for surgical and soft tissue applications

Evidence statusInsufficient evidence for many wound indications; RCTs limited or lacking

VariantsIncludes AmnioFix Injectable for tendon/soft tissue injections (limited evidence)

inv-163: Apis — product description

Product descriptionApis: absorbable, biodegradable skin substitute composed of porcine gelatin, Manuka honey, and hydroxyapatite intended to protect wounds and manage exudate

Evidence statusFew published studies; clinical benefit not established

Intended useProtect large or nonhealing wounds or burns

inv-164: Apis (SweetBio, Inc) — product description

Product detailsApis (SweetBio, Inc): porcine gelatin + Manuka honey + hydroxyapatite biodegradable skin substitute

Evidence summaryFew studies; insufficient evidence to conclude clinical benefit

Intended applicationWound protection and exudate management

inv-165: Artacent family (Tides Medical) — product description

Product familyArtacent family (Tides Medical): dehydrated human amniotic allograft products intended as wound coverings for acute and chronic wounds

Evidence statusFew published studies; limited observational data (one small observational analysis reported 65% closure in 26 subjects)

Intended usesDiabetic ulcers, pressure ulcers, venous stasis ulcers, burns per manufacturer claims

inv-166: Biovance (Celularity) — product description

Product descriptionBiovance (Celularity): decellularized, dehydrated human amniotic membrane (DDHAM) intended for acute and chronic wounds

Registry evidenceMulticenter registry (Smiell et al. 2015): 179 chronic wounds, ~50% closure, median 6.3 weeks; limitations noted

Study exclusionsRegistry excluded actively infected wounds and known hypersensitivity to DDHAM

inv-167: DDHAM — decellularized dehydrated human amniotic membrane definition

DefinitionDDHAM (Decellularized, dehydrated human amniotic membrane): amniotic membrane processed to remove cells and dehydrated for wound covering use

Example productBiovance is cited as a DDHAM product evaluated in a multicenter registry

Intended roleSupport wound closure across various chronic wound types as adjunct to usual care

inv-168: Porcine SIS-ECM — definition

DefinitionPorcine SIS-ECM: non-cross-linked extracellular matrix derived from porcine small intestinal submucosa intended to promote tissue ingrowth/regeneration

Example productCorMatrix is an example of porcine SIS-ECM used in various surgical applications

Clinical cautionEvidence for specific applications is limited and safety signals reported in some cardiac series

inv-169: CorMatrix — product description

Product descriptionCorMatrix: non-cross-linked porcine small intestinal submucosa ECM used in cardiac and other applications

Evidence concernsInsufficient evidence for many uses; cardiac series reported high reoperation/patch-failure rates in some studies

Clinical implicationSafety/efficacy not established for broad clinical use in wounds without further data

inv-170: Corplex — product description

Product descriptionCorplex: dehydrated human umbilical cord tissue sheet used as wound covering or barrier membrane for acute and chronic wounds

Evidence statusFew published studies; insufficient evidence to conclude benefit

Intended useWound coverage and barrier applications

inv-171: DermACELL / D-ADM — product description

Product familyDermACELL / D-ADM: decellularized human acellular dermal matrices intended for chronic non-healing wounds

RCT evidenceRandomized trials including a 16-week multicenter RCT demonstrated higher healed ulcer rates vs conventional care (67.9% vs 47.8%)

Coverage implicationEvidence supports consideration of DermACELL when wound characteristics align with study populations

inv-172: DermACELL — product description

Product descriptionDermACELL: human acellular dermal matrix evaluated in a 16-week multicenter RCT for full-thickness DFUs

Key trial resultsHigher healed ulcer rate and greater percent area reduction vs conventional care; one or two applications allowed

Evidence caveatStudy sponsored by manufacturer; additional independent trials desirable

inv-173: EpiCord — product description

Product descriptionEpiCord: dehydrated, non-viable cellular umbilical cord allograft intended for chronic and acute wounds

RCT evidenceMulticenter RCT showed higher 12-week healing rates vs alginate dressings (70% vs 48% ITT) with markedly higher healing when adequately debrided

Inclusion ulcer size1–15 cm²; 14-day run-in selecting nonresponders prior to randomization

inv-174: EPIEFFECT — product description

Product descriptionEPIEFFECT: lyophilized human placental-based allograft membrane including amnion, intermediate, and chorion layers as protective barrier

Evidence statusFew published studies; insufficient evidence to conclude benefit

Intended useBarrier in acute and chronic wounds

inv-175: EpiFix Injectable / EpiFix (non-injectable) — product description

Product formsEpiFix Injectable: micronized powder; EpiFix (non-injectable): dehydrated amnion/chorion membrane extracellular collagen allograft

Evidence statusNon-injectable EpiFix has multiple studies showing improved healing as adjunct to SOC; injectable form has few studies and evidence limited

Application notesEpiFix (non-injectable) applied weekly in many RCTs; injectable form used in other soft tissue indications with limited data

inv-176: EPIXPRESS — product description

Product descriptionEPIXPRESS: minimally manipulated, lyophilized, non-viable cellular allograft derived from human amniotic membrane preserving ECM components

Evidence statusFew published studies; insufficient evidence to conclude benefit

Intended useWound coverage applications; evidence limited

inv-177: Grafix (vCPM, hVWM) — product description

Product descriptionGrafix (vCPM, hVWM): cryopreserved placental membrane containing ECM, growth factors, and viable cells intended to promote wound healing

Evidence summaryMultiple RCTs and observational studies suggest Grafix may improve healing in chronic wounds; comparative effectiveness remains uncertain

Application frequencyGrafix limited to one application per week for up to 12 weeks per policy

inv-178: EpiFix (dHACM) — product description

Product descriptionEpiFix (dHACM): dehydrated human amnion/chorion membrane allograft used as adjunct to compression or standard care

RCT outcomesRCTs report improved short-term healing rates (eg, VLU trial: 60% vs 35% at 12 weeks) but larger confirmatory trials recommended

Typical applicationWeekly application in trials as adjunct to SOC/compression

inv-179: Grafix Core — product description

Product descriptionGrafix Core: cryopreserved chorion matrix (Smith & Nephew) with limited published evidence

Evidence statusFew studies; clinical benefit not established

Intended useWound covering applications; product info limited

inv-180: Grafix Plus — product description

Product descriptionGrafix Plus: lyophilized human placental chorionic membrane-based skin substitute for acute and chronic wounds

Evidence statusStudies lacking; insufficient evidence to conclude benefit

Intended applicationsWound cover, wrap, barrier including surgically created wounds

inv-181: Helicoll — product description

Product descriptionHelicoll: semi-occlusive, self-adhering collagen sheet derived from animal tissues for wound treatment, burns, and chronic ulcers

Evidence statusLimited studies; evidence inconclusive

Potential usesTreatment of partial-thickness burns and chronic ulcers; pediatric evidence emerging but limited

inv-182: Hyalomatrix — product description

Product descriptionHyalomatrix: hyaluronic acid–derived fibrous wound contact layer with semipermeable silicone outer layer intended for various wounds

Evidence statusSeveral non-comparative studies with limitations; clinical benefit not conclusively established

IndicationsManagement of various wounds; evidence inconclusive per ECRI assessments

inv-183: Integra Flowable Wound Matrix — product description

Product descriptionIntegra Flowable Wound Matrix: flowable matrix of cross-linked bovine collagen and glycosaminoglycan for deep or tunneling wounds

Evidence statusSeveral studies exist but with limitations; evidence inconclusive regarding clinical benefit

Use caseIntended for deep/tunneling wounds; some small RCTs report benefit but excluded from some reviews due to SOC criteria

inv-184: Fish skin graft (FSG) — product description

Product descriptionFish skin graft (FSG, Kerecis): xenogenic acellular skin substitute derived from North Atlantic cod intended as adjunct to SOC to promote healing

RCT evidenceRCTs (eg, Lullove 2021) reported higher closure rates vs SOC in DFUs but studies are small; evidence evolving

Ongoing researchAdditional RCTs and trials are ongoing to address evidence gaps

inv-185: Acellular dermal matrix — definition

DefinitionAcellular dermal matrix: 3D scaffold composed of collagen/elastin or other proteins intended to support tissue regeneration when applied to wounds

Common sourcesHuman, bovine, or other animal-derived matrices used as dermal scaffolds

Clinical roleSupport tissue ingrowth and regeneration as adjunct to wound care or grafting

inv-186: MatriDerm — product description

Product descriptionMatriDerm: single-use 3D acellular dermal matrix composed of bovine collagen and elastin for full/partial thickness wounds and chronic wounds

Evidence statusSeveral studies with limitations; evidence not conclusive

Indicated usesBurns, donor sites, chronic wounds, surgical wounds per product labeling and studies

inv-187: Matrion — product description

Product descriptionMatrion: regenerative human placental allograft (decellularized placental membrane) available in membrane, injectable, and sponge forms

Evidence statusFew published studies; insufficient evidence to conclude clinical benefit

Intended usesModulate inflammation and enhance healing in wounds, tendon, nerve applications

inv-188: Mirragen (BBGFM) — product description

Product descriptionMirragen (BBGFM): synthetic resorbable wound matrix of borate-based glass fibers and particulates designed as scaffold for revascularization

RCT evidenceSmall RCT (Armstrong 2022) reported improved healing and percent area reduction in Wagner 1 DFUs at 12 weeks vs SOC (70% vs 25%)

Evidence caveatPromising results but limited by small sample size and study weaknesses; further studies needed