BlueCross BlueShield of Tennessee Medical Policy Manual

Bioengineered Skin and Soft Tissue Substitutes

DESCRIPTION

Bio-engineered skin and soft tissue substitutes may be derived from human tissue (autologous or allogeneic), nonhuman tissue (xenographic), synthetic materials, or a composite of these materials. Bioengineered skin and soft tissue substitutes are being evaluated for a variety of conditions, including breast reconstruction and to facilitate healing of lower-extremity ulcers and severe burns. The gold standard for surgical wound repair is to use a skin graft harvested from the patient’s own skin (autograft). However, autologous tissue grafting is an invasive and painful procedure, and the extent of damaged skin can be too large to be covered by an autologous graft alone.

While there are many proposed applications for these products the evidence on any single product is extremely limited. FDA approval is obtained as premarket approval, 510(k) clearance, humanitarian device exemption (HDE) or regulated as banked human tissue depending on the source of the product.

Note: Please see Human Amniotic Membrane Grafts and Amniotic Fluid Injections medical policy for all products using human amniotic membrane or amniotic fluid.

POLICY 

    • ACell® UBM Hydrated Wound Dressing

    • AlloSkin™

    • AlloSkin™ AC 

    • AlloSkin™ RT

    • Aongen™ Collagen Matrix

    • Architect® ECM, PX, FX

    • ArthroFlex™ (FlexGraft)

    • Atlas Wound Matrix

    • Avagen Wound Dressing

    • AxoGuard® Nerve Protector / Avance® Nerve Graft

    • Biobrane®

    • bio-ConneKt Wound Matrix

    • CellerateRX® /CRXa™

    • CollaCare®

    • CollaCare® Dental

    • Collagen Wound Dressing (Oasis Research)

    • CollaGUARD®

    • CollaMend™

    • CollaWound™ Collagen Granules

    • Collexa® 

    • Collieva®

    • Conexa™

    • Colla-Pad (Corleader)

    • CorMatrix®

    • CRXa™ / CellerateRX®

    • Cymetra® Micronized AlloDerm® Tissue, injectible

    • Cytal™

    • DermADAPT™ Wound Dressing

    • Dermapure™

    • DermaSpan™

    • DressSkin™

    • Durepair® Regeneration Matrix

    • Endoform Dermal Template™

    • ENDURAGen™

    • Excellagen

    • ExpressGraft™

    • E-Z Derm™

    • FlexiGraft®

    • FlowerDerm™– still with active website

    • FortaDerm™ Wound Dressing / Puraply™

    • GammaGraft

    • GraftJacket® Xpress, injectable

    • Helicoll™

  • Hyalomatrix® Tissue Reconstruction Matrix

  • Hyalomatrix® PA

  • hMatrix® PR

  • Integra™ Bilayer Wound Matrix

  • Keramatrix

  • Kerecis™ Omega3 Wound

  • MariGen™ Omega3 Wound

  • MatriDerm®

  • MatriStem® Burn Matrix / Cytal™ Burn Matrix (ACell)

  • MatriStem® Micromatrix (ACell)

  • MatriStem® Wound Matrix / Cytal™ Wound Matrix (ACell)

  • Matrix HD™Allograft / Matrix HD™ Allograft Fenestrated

  • MediSkin®

  • MemoDerm™

  • MIRODERM® (Microderm Biologic Wound Matrix)

  • NeoForm™

  • NuCel

  • Oasis® Burn Matrix

  • Oasis® Ultra

  • Pelvicol® / PelviSoft™

  • Permacol™ Surgical Implant

  • PriMatrix™ AG

  • Primatrix™ Dermal Repair Scaffold

  • PuraPly™ Wound Dressing / FortaDerm™

  • PuraPly™ Antimicrobial

  • Puros® Dermis

  • RegenePro™

  • Repliform®

  • Repriza™

  • StrataGraft®

  • Strattice™ Reconstructive Tissue Matrix

  • Suprathel®

  • SurgiMend®

  • Talymed®

  • TenoGlide™

  • TenSIX™ Acellular Dermal Matrix

  • TheraForm™ Standard/Sheet

  • TheraSkin®

  • TissueMend

  • TruSkin™

  • Unite® Biomatrix

  • Veritas® Collagen Matrix

  • XCM BIOLOGIC® Tissue Matrix

  • XenMatrix™

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION

Overall, the number of bio-engineered skin and soft-tissue substitutes is large, but the evidence is limited for any specific product. Relatively few products have been compared with the standard of care (SOC), and then only for some indications. Therefore, many of these products remain investigational.

SOURCES

Agency for Healthcare Research and Quality (AHRQ). (2012, December). Skin substitutes for treating chronic wounds. Retrieved January 27, 2014 from: http://www.ahrq.gov.

American Society of Plastic Surgeons. (2013, March). Evidenced-based clinical practice guideline: Breast reconstruction with expanders and implants. Retrieved January 27, 2014 from: http://www.plasticsurgery.org.

BlueCross BlueShield Association. Evidence Positioning System. (2:2019). Bio-engineered skin and soft tissue substitutes (7.01.113). Retrieved February 25, 2019 from http://www.evidencepositioningsystem.com. (64 articles and/or guidelines reviewed)

Campitiello, F., Mancone, M., Della Corte, A., Guerniero, R., and Canonico, S. (2017, December) To evaluate the efficacy of an acellular Flowable matrix in comparison with a wet dressing for the treatment of patients with diabetic foot ulcers: a randomized clinical trial. Updates in Surgery, 69 (4), 523-529. Abstract retrieved March 15, 2018 from PubMed database.

Chang, E. and Liu, J. (2017, September). Prospective unbiased experience with three acellular dermal matrices in breast reconstruction. Journal of Surgical Oncology, 116 (3), 365-370. Abstract retrieved March 15, 2018 from PubMed database.

Code of Federal Regulations. (2017) Title 21: Food and Drugs. PART 127 - Human cells, tissues, and cellular and tissue based products. Received February 7, 2017 from http://www.ecfr.gov/cgi-bin/text.

Davila, A. A., Seth, A. K., Wang, E., Hanwright, P., Bilimoria, K., Fine, N., et al. (2013). Human acellular dermis versus submuscular tissue expander breast reconstruction: A multivariate analysis of short-term complications. Archives of Plastic Surgery, 40 (1), 19-27. (Level 1 evidence - Industry sponsored)

DiDomenico, L., Landsman, A., Emch, K. and Landsman, A. (2011, July) A prospective comparison of diabetic foot ulcers treated with either a cryopreserved skin allograft or a bioengineered skin substitute. Wounds. 2011:23(7):184-9. Abstract retrieved February 20, 2017 from PubMed database.

Driver, V., Lavery, L., Reyzelman, A., Dutra, T., Dove, C., Kotsis, S., et. al. (2015, August) A clinical trial of Integra Template for diabetic foot ulcer treatment. Wound Repair and Regeneration(2015) 23 891-900. (Level 1 evidence)

ECRI Institute. Health Technology Assessment. Product Brief. (2018, October). TheraSkin human skin allograft (Solsys Medical, LLC) for treating surgical and chronic wounds. Retrieved February 25, 2019 from ECRI Institute. (7 articles and/or guidelines reviewed)

ECRI Institute. Health Technology Assessment. Product Brief. (2018, March). Dermacell advanced decellularized dermis (LifeNet Health Bio-Implants Division) for breast reconstruction. Retrieved March 15, 2018 from ECRI Institute. (7 articles and/or guidelines reviewed)

Frykberg, R., Gibbons, G., Walters, J., Wukich, D., and Milstein, F. (2016) A prospective, multicentre, open-label, single-arm clinical trial for treatment of chronic complex diabetic foot wounds with exposed tendon and/or bone: positive clinical outcomes of viable cryopreserved human placental membrane. International Wound Journal ISSN 1742-4801. (Level 2 evidence)

Gibbons, G. (2015) Grafix® a cryopreserved placental membrane for the treatment of chronic/stalled wounds. Advances in Wound Care. Vol. 4, No. 9; 434-444. (Level 4 evidence - Industry sponsored)

Infectious Diseases Society of America (2012. June) 2012 Clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Retrieved January 27, 2014 from http://www.guidelines.gov.

Landsman, A.S., Cook, J., Cook, E., Landsman, A.R., Garrett, P., Yoon, J., et. al., (2011, February) A retrospective clinical study of 188 consecutive patients to examine the effectiveness of a biologically active cryopreserved human skin allograft (TheraSkin®) on the treatment of diabetic foot ulcers and venous leg ulcers. Foot & Ankle Specialist; 4(1):29-41. Abstract retrieved July 11, 2016 from PubMed database.

Lavery, L., Fulmer, J., Shebetka, K., Regulski, M., Vayser, D., Fried, D, et. al., (2014) The efficacy and safety of Grafix® for the treatment of chronic diabetic foot ulcers: results of a multi-centre, controlled, randomised, blinded, clinical trial. International Wound Journal ISSN 1742-4801. (Level 2 evidence -. Industry sponsored)

National Institute for Health and Clinical Excellence (NICE). (2016, January). Diabetic foot problems: prevention and management. Retrieved March 19, 2018 from http://www.nice.org.uk.

Pittman, T., Fan, K., Knapp, A., Frantz, S., and Spear, S. (2017, March). Comparison of Different Acellular Dermal Matrices in Breast Reconstruction: The 50/50 Study. Plastics & Reconstructive Surgery, 139 (3), 521-528. Abstract retrieved March 15, 2018 from PubMed database.

Regulski, M., Jacobstein, J., Petranto, R., Migliori, V., Nair, G., and Pfeiffer, H. (2013, December) A retrospective analysis of human cellular repair matrix for the treatment of chronic wounds. Ostomy Wound Management. 2013; 59(12):38-43. (Level 4 evidence)

Sanders, L., Landsman, A., Landsman, A., Keller, N. Cook, J., Cook, J., et. al., (September, 2014). A prospective, multicenter, randomized controlled clinical trial comparing a bioengineered skin substitute to a human skin allograft. Ostomy Wound Management: 60(9):26-38. (Level 2 evidence)

Towler, M., Rush, E., Richardson, M., and Williams, C. (2018, July) Randomized, prospective, blinded-enrollment, head-To-head venous leg ulcer healing trial comparing living, bioengineered skin graft substitute (Apligraf) with living, cryopreserved, human skin allograft (TheraSkin). Clinics in Podiatry Medicine & Surgery, 35 (3), 357-365. Abstract retrieved February 25, 2019 from PubMed database.

U. S. Food and Drug Administration. (2001, August). Center for Devices and Radiological Health. Cellular Matrix - P010016 (OrCel™ Bilayered). Retrieved January 31, 2014 from http://www.accessdata.fda.gov.

U. S. Food and Drug Administration. (2006, July). Center for Devices and Radiological Health. Premarket Approval Database. P950032/S016 (Apligraf®). Retrieved January 31, 2014 from http://www.accessdata.fda.gov.

U. S. Food and Drug Administration. (2007, October). Center for Devices and Radiological Health. Epicel® (cultured epidermal autografts) - H990002. Retrieved January 31, 2014 from http://www.accessdata.fda.gov.

Winifred S. Hayes, Inc. Medical Technology Directory. (2017, November; last update search November 2018). Skin substitutes for chronic foot ulcers in adults with diabetes mellitus: a review of reviews. Retrieved February 25, 2019 from www.Hayesinc.com. (21 articles and/or guidelines reviewed)

Winifred S. Hayes, Inc. Medical Technology Directory. (2017, November; last update search November 2018). Comparative effectiveness of skin substitutes for chronic venous leg ulcers in adults: a review of reviews. Retrieved February 25, 2019 from www.Hayesinc.com. (24 articles and/or guidelines reviewed)

ORIGINAL EFFECTIVE DATE:  8/11/2012

MOST RECENT REVIEW DATE:  4/11/2019

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