Bioengineered Skin and Soft Tissue Substitutes
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.
Bioengineered skin and soft tissue substitutes are considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
All other uses of bio-engineered skin and soft tissue substitutes are considered investigational.
All other skin and soft tissue substitutes, including, but not limited to the following, are considered investigational:
Any product utilized for this procedure must have FDA approval specific to the indication, otherwise it will be considered investigational.
Bioengineered skin and soft tissue substitutes are considered medically appropriate if ANY ONE of the following criteria are met:
Treatment for breast reconstructive surgery using allogenic acellular dermal matrix products including each of the following: AlloDerm® Regenerative Tissue Matrix; Cortiva®, (AlloMax™ Surgical Graft); AlloMend®; DermACELL®; DermMatrix™; FlexHD®; FlexHD Pliable®; or GraftJacket® if ANY ONE of the following criteria are met:
There is insufficient tissue expander or implant coverage by the pectoralis major muscle and additional coverage is required
There are viable but compromised or thin postmastectomy skin flaps that are at risk of dehiscence or necrosis
The infra-mammary fold and lateral mammary folds have been undermined during mastectomy and re-establishment of these landmarks is needed
Treatment of chronic, non-infected, full-thickness diabetic lower extremity ulcers using ANY ONE of the following tissue-engineered skin substitutes:
Integra® Dermal Regeneration Template or
Integra Omnigraft™ Dermal Regeneration Matrix
Integra® Flowable Wound Matrix
Treatment of chronic, non-infected, partial- or full-thickness lower extremity skin ulcers due to venous insufficiency, which have not adequately responded following a 30 day period of conventional ulcer therapy, using ANY ONE of the following tissue-engineered skin substitutes:
Oasis™ Wound Matrix
Treatment of dystrophic epidermolysis bullosa using OrCel™ for individuals with mitten-hand deformity when ALL of the following criteria are met:
Standard wound therapy has failed
Provided in accordance with the Humanitarian Device Exemption (HDE) specifications of the FDA
Treatment of second- and third-degree burns using ANY ONE of the following tissue-engineered skin substitutes:
Epicel® when ALL of the following criteria are met:
For the treatment of deep dermal or full-thickness burns comprising a total body surface area of greater than or equal to 30%
Provided in accordance with the Humanitarian Device Exemption (HDE) specifications of the FDA
Integra Dermal Regeneration Template™
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
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.
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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