Comparison of Skin Substitutes for Acute and Chronic Wound Management

Caroline Bay; Zachary Chizmar; Edward M. Reece; Jessie Z. Yu; Julian Winocour; Joshua Vorstenbosch; Sebastian Winocour

doi:10.1055/s-0041-1731463

Seminars in Plastic Surgery, Table of Contents

Semin Plast Surg 2021; 35(03): 171-180
DOI: 10.1055/s-0041-1731463

Review Article

Comparison of Skin Substitutes for Acute and Chronic Wound Management

Caroline Bay

¹Michael E. DeBakey Department of Surgery, Division of Plastic Surgery, Baylor College of Medicine, Houston, Texas

,

Zachary Chizmar

²Michael E. DeBakey Department of Surgery, Division of General Surgery, Baylor College of Medicine, Houston, Texas

,

Edward M. Reece

¹Michael E. DeBakey Department of Surgery, Division of Plastic Surgery, Baylor College of Medicine, Houston, Texas

³Division of Plastic Surgery, Texas Children's Hospital, Houston, Texas

,

Jessie Z. Yu

¹Michael E. DeBakey Department of Surgery, Division of Plastic Surgery, Baylor College of Medicine, Houston, Texas

,

Julian Winocour

⁴Department of Plastic Surgery, Vanderbilt University, Nashville, Tennessee

,

Joshua Vorstenbosch

⁵Division of Plastic Surgery, McGill University, Montreal, Canada

,

Sebastian Winocour

¹Michael E. DeBakey Department of Surgery, Division of Plastic Surgery, Baylor College of Medicine, Houston, Texas

› Author Affiliations

Abstract

Chronic and acute wounds, such as diabetic foot ulcers and burns, respectively, can be difficult to treat, especially when autologous skin transplantations are unavailable. Skin substitutes can be used as a treatment alternative by providing the structural elements and growth factors necessary for reepithelialization and revascularization from a nonautologous source. As of 2020, there are 76 commercially available skin substitute products; this article provides a review of the relevant literature related to the major categories of skin substitutes available.

Keywords

skin substitutes - chronic wound treatment - acute wound treatment - dermal replacement - epidermal replacement

Full Text

References

References
1 Shahrokhi S. Skin substitutes. In: Jeschke MG, Collins KA. eds. UpToDate. UpToDate; ; February 22, 2021. Accessed February 22, 2021 at: https://www.uptodate.com/contents/skin-substitutes
2 Nicholas MN, Yeung J. Current status and future of skin substitutes for chronic wound healing. J Cutan Med Surg 2017; 21 (01) 23-30
3 Snyder D, Sullivan N, Margolis D. et al. Skin substitutes for treating chronic wounds [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); ; Published February 2, 2020. Accessed April 10, 2021 at. https://www.ncbi.nlm.nih.gov/books/NBK554222/
4 Davison-Kotler E, Sharma V, Kang NV, García-Gareta E. A universal classification system of skin substitutes inspired by factorial design. Tissue Eng Part B Rev 2018; 24 (04) 279-288
5 Braza ME, Fahrenkopf MP. Split-thickness skin grafts. In: StatPearls. StatPearls Publishing; 2021. . Accessed April 11, 2021 at: http://www.ncbi.nlm.nih.gov/books/NBK551561/
6 Leon-Villapalos J, Dziewulski P. Skin autografting. In: Butler CE, Jeschke MG, Collins KA. eds. UpToDate. UpToDate; ; February 3, 2021. Accessed April 21, 2021 at: https://www.uptodate.com/contents/skin-autografting#H50049672
7 Ramsey ML, Walker B, Patel BC. Full thickness skin grafts. In: StatPearls. StatPearls Publishing; 2021. . Accessed April 28, 2021 at: http://www.ncbi.nlm.nih.gov/books/NBK532875/
8 Hickerson WL, Remmers AE, Recker DP. Twenty-five years' experience and beyond with cultured epidermal autografts for coverage of large burn wounds in adult and pediatric patients, 1989–2015. J Burn Care Res 2019; 40 (02) 157-165
9 Epicel (cultured epidermal autografts). FDA; . Published March 7, 2018. Accessed April 28, 2021 at: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/epicel-cultured-epidermal-autografts
10 Ronfard V, Rives JM, Neveux Y, Carsin H, Barrandon Y. Long-term regeneration of human epidermis on third degree burns transplanted with autologous cultured epithelium grown on a fibrin matrix. Transplantation 2000; 70 (11) 1588-1598
11 Leon-Villapalos J, Dziewulski P. Overview of surgical procedures used in the management of burn injuries. In: Jeschke MG, Butler CE, Collins KA. eds. UpToDate. UpToDate; ; January 29, 2020. Accessed January 29, 2020 at: https://www.uptodate.com/contents/overview-of-surgical-procedures-used-in-the-management-of-burn-injuries
12 Dhivya S, Padma VV, Santhini E. Wound dressings - a review. Biomedicine (Taipei) 2015; 5 (04) 22
13 Bullocks JM. DermACELL: a novel and biocompatible acellular dermal matrix in tissue expander and implant-based breast reconstruction. Eur J Plast Surg 2014; 37 (10) 529-538
14 Arnaout A, Zhang J, Frank S. et al; On Behalf Of The REaCT Investigators. A randomized controlled trial comparing Alloderm-RTU with DermACELL in immediate subpectoral implant-based breast reconstruction. Curr Oncol 2020; 28 (01) 184-195
15 Pruitt Jr BA, Levine NS. Characteristics and uses of biologic dressings and skin substitutes. Arch Surg 1984; 119 (03) 312-322
16 Clarke JA. HIV transmission and skin grafts. Lancet 1987; 1 (8539): 983
17 AlloDerm Regenerative Tissue Matrix. Published online November 2008. https://c1-preview.prosites.com/44184/wy/docs/MLD102.pdf
18 Cazzell S. A randomized controlled trial comparing a human acellular dermal matrix versus conventional care for the treatmentof venous leg ulcers. Wounds 2019; 31 (03) 68-74
19 Capito AE, Tholpady SS, Agrawal H, Drake DB, Katz AJ. Evaluation of host tissue integration, revascularization, and cellular infiltration within various dermal substrates. Ann Plast Surg 2012; 68 (05) 495-500
20 GRAFTJACKET Regenerative Tissue Matrix. Published online November 2015. https://www.wright.com/wp-content/uploads/2015/04/GJ_ifu_121P0129m_T6.pdf
21 Reyzelman A, Crews RT, Moore JC. et al. Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study. Int Wound J 2009; 6 (03) 196-208
22 Guo X, Mu D, Gao F. Efficacy and safety of acellular dermal matrix in diabetic foot ulcer treatment: A systematic review and meta-analysis. Int J Surg 2017; 40: 1-7
23 Adetayo OA, Salcedo SE, Bahjri K, Gupta SC. A Meta-analysis of Outcomes Using Acellular Dermal Matrix in Breast and Abdominal Wall Reconstructions: Event Rates and Risk Factors Predictive of Complications. Ann Plast Surg 2016; 77 (02) e31-e38
24 Glasberg SB, D'Amico RA. Use of regenerative human acellular tissue (AlloDerm) to reconstruct the abdominal wall following pedicle TRAM flap breast reconstruction surgery. Plast Reconstr Surg 2006; 118 (01) 8-15
25 Clemens MW, Kronowitz SJ. Acellular dermal matrix in irradiated tissue expander/implant-based breast reconstruction: evidence-based review. Plast Reconstr Surg 2012; 130 (5, Suppl 2) 27S-34S
26 Greig H, Roller J, Ziaziaris W, Van Laeken N. A retrospective review of breast reconstruction outcomes comparing AlloDerm and DermaCELL. JPRAS Open 2019; 22: 19-26
27 DiDomenico LA, Orgill DP, Galiano RD. et al. Aseptically processed placental membrane improves healing of diabetic foot ulcerations: prospective, randomized clinical trial. Plast Reconstr Surg Glob Open 2016; 4 (10) e1095
28 Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care (New Rochelle) 2015; 4 (09) 560-582
29 AmnioRepair Allograft. Published 2020. Accessed April 18, 2021 at: https://www.zimmerbiomet.com/content/dam/zimmer-biomet/medical-professionals/foot-and-ankle/amniorepair-allograft/3013.1-US-en-AmnioRepair-Flyer.pdf
30 Ahuja N, Jin R, Powers C, Billi A, Bass K. Dehydrated human amnion chorion membrane as treatment for pediatric burns. Adv Wound Care (New Rochelle) 2020; 9 (11) 602-611
31 Bianchi C, Tettelbach W, Istwan N. et al. Variations in study outcomes relative to intention-to-treat and per-protocol data analysis techniques in the evaluation of efficacy for treatment of venous leg ulcers with dehydrated human amnion/chorion membrane allograft. Int Wound J 2019; 16 (03) 761-767
32 Tettelbach W, Cazzell S, Reyzelman AM, Sigal F, Caporusso JM, Agnew PS. A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers: A prospective, multicentre, randomised, controlled study of 110 patients from 14 wound clinics. Int Wound J 2019; 16 (01) 19-29
33 Glat P, Orgill DP, Galiano R. et al. A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers: a prospective, multicentre, randomised, controlled study of 110 patients from 14 wound clinics. Int Wound J 2019; 7 (08) e2371
34 Snyder RJ, Shimozaki K, Tallis A. et al. A prospective, randomized, multicenter, controlled evaluation of the use of dehydrated amniotic membrane allograft compared to standard of care for the closure of chronic diabetic foot ulcer. Wounds 2016; 28 (03) 70-77
35 Bianchi C, Cazzell S, Vayser D, Reyzelman AM, Dosluoglu H, Tovmassian G. EpiFix VLU Study Group. A multicentre randomised controlled trial evaluating the efficacy of dehydrated human amnion/chorion membrane (EpiFix^® ) allograft for the treatment of venous leg ulcers. Int Wound J 2018; 15 (01) 114-122
36 Kirsner RS, Sabolinski ML, Parsons NB, Skornicki M, Marston WA. Comparative effectiveness of a bioengineered living cellular construct vs. a dehydrated human amniotic membrane allograft for the treatment of diabetic foot ulcers in a real world setting. Wound Repair Regen 2015; 23 (05) 737-744
37 King TW, Butler CE. Implants and biomaterials. In: Plastic Surgery: Volume 1: Principles. Vol 1. 4th ed.. Elsevier Inc.; 2018: 595-604.e2 . Available at: https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323356947000308
38 Integra Dermal Regeneration Template. Published 2012. Accessed April 22, 2021 at: https://www.integralife.com/file/general/1453795605-1.pdf
39 Koenen W, Felcht M, Vockenroth K, Sassmann G, Goerdt S, Faulhaber J. One-stage reconstruction of deep facial defects with a single layer dermal regeneration template. J Eur Acad Dermatol Venereol 2011; 25 (07) 788-793
40 Nguyen TT, Gilpin DA, Meyer NA, Herndon DN. Current treatment of severely burned patients. Ann Surg 1996; 223 (01) 14-25
41 Groos N, Guillot M, Zilliox R, Braye FM. Use of an artificial dermis (Integra) for the reconstruction of extensive burn scars in children. About 22 grafts. Eur J Pediatr Surg 2005; 15 (03) 187-192
42 Dantzer E, Braye FM. Reconstructive surgery using an artificial dermis (Integra): results with 39 grafts. Br J Plast Surg 2001; 54 (08) 659-664
43 Yeong E-K, Chen S-H, Tang Y-B. The treatment of bone exposure in burns by using artificial dermis. Ann Plast Surg 2012; 69 (06) 607-610
44 Rehim SA, Singhal M, Chung KC. Dermal skin substitutes for upper limb reconstruction: current status, indications, and contraindications. Hand Clin 2014; 30 (02) 239-252
45 Heimbach DM, Warden GD, Luterman A. et al. Multicenter postapproval clinical trial of Integra dermal regeneration template for burn treatment. J Burn Care Rehabil 2003; 24 (01) 42-48
46 Vig K, Chaudhari A, Tripathi S. et al. Advances in skin regeneration using tissue engineering. Int J Mol Sci 2017; 18 (04) E789
47 Whitaker IS, Prowse S, Potokar TS. A critical evaluation of the use of Biobrane as a biologic skin substitute: a versatile tool for the plastic and reconstructive surgeon. Ann Plast Surg 2008; 60 (03) 333-337
48 Pinto Medeiros Dias MT, Lima Júnior EM, Negreiros Nunes Alves AP. et al. Tilapia fish skin as a new biologic graft for neovaginoplasty in Mayer-Rokitansky-Kuster-Hauser syndrome: a video case report. Fertil Steril 2019; 112 (01) 174-176
49 Alam K, Jeffery SLA. Acellular fish skin grafts for management of split thickness donor sites and partial thickness burns: a case series. Mil Med 2019. Mil Med 2019; 184 (Suppl. 01) 16-20
50 Lima-Junior EM, de Moraes Filho MO, Costa BA. et al. Innovative treatment using tilapia skin as a xenograft for partial thickness burns after a gunpowder explosion. J Surg Case Rep 2019; 2019 (06) rjz181
51 Chen J, Gao K, Liu S. et al. Fish collagen surgical compress repairing characteristics on wound healing process in vivo. Mar Drugs 2019; 17 (01) E33
52 Badois N, Bauër P, Cheron M. et al. Acellular fish skin matrix on thin-skin graft donor sites: a preliminary study. J Wound Care 2019; 28 (09) 624-628
53 Kerecis Omega3 Wound Instructions for Use. Accessed April 21, 2021 at: https://www.kerecis.com/wp-content/uploads/2020/11/Instructions-for-Use-IFU.pdf
54 Prescription Products - Omega3 Wound. Kerecis. Accessed April 21, 2021 at: https://www.kerecis.com/omega3-wound
55 Kirsner RS, Margolis DJ, Baldursson BT. et al. Fish skin grafts compared to human amnion/chorion membrane allografts: A double-blind, prospective, randomized clinical trial of acute wound healing. Wound Repair Regen 2020; 28 (01) 75-80
56 Dias MTPM, Bilhar APM, Rios LC. et al. Neovaginoplasty using Nile tilapia fish skin as a new biologic graft in patients with Mayer-Rokitansky-Küster-Hauser Syndrome. J Minim Invasive Gynecol 2020; 27 (04) 966-972
57 Michael S, Winters C, Khan M. Acellular fish skin graft use for diabetic lower extremity wound healing: a retrospective study of 58 ulcerations and a literature review. Wounds 2019; 31 (10) 262-268
58 Stone RC, Stojadinovic O, Rosa AM. et al. A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers. Sci Transl Med 2017; 9 (371) eaaf8611
59 Veves A, Falanga V, Armstrong DG, Sabolinski ML. Apligraf Diabetic Foot Ulcer Study. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care 2001; 24 (02) 290-295
60 Sams HH, Chen J, King LE. Graftskin treatment of difficult to heal diabetic foot ulcers: one center's experience. Dermatol Surg 2002; 28 (08) 698-703
61 Chang DW, Sanchez LA, Veith FJ, Wain RA, Okhi T, Suggs WD. Can a tissue-engineered skin graft improve healing of lower extremity foot wounds after revascularization?. Ann Vasc Surg 2000; 14 (01) 44-49
62 Falanga V, Margolis D, Alvarez O. et al; Human Skin Equivalent Investigators Group. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Arch Dermatol 1998; 134 (03) 293-300
63 Martinson M, Martinson N. A comparative analysis of skin substitutes used in the management of diabetic foot ulcers. J Wound Care 2016; 25 (Suppl. 10) S8-S17
64 Rice JB, Desai U, Ristovska L. et al. Economic outcomes among Medicare patients receiving bioengineered cellular technologies for treatment of diabetic foot ulcers. J Med Econ 2015; 18 (08) 586-595
65 Samsell B, McLean J, Cazzell S, Dorsch K, Moyer PM, Moore M. Health economics for treatment of diabetic foot ulcers: a cost-effectiveness analysis of eight skin substitutes. J Wound Care 2019; 28 (Suppl. 09) S14-S26
66 Zelen CM, Serena TE, Gould L. et al. Treatment of chronic diabetic lower extremity ulcers with advanced therapies: a prospective, randomised, controlled, multi-centre comparative study examining clinical efficacy and cost. Int Wound J 2016; 13 (02) 272-282
67 Towler MA, Rush EW, Richardson MK, Williams CL. 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). Clin Podiatr Med Surg 2018; 35 (03) 357-365
68 Landsman AS, Cook J, Cook E. et al. 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 Spec 2011; 4 (01) 29-41
69 Gurtner GC, Garcia AD, Bakewell K, Alarcon JB. A retrospective matched-cohort study of 3994 lower extremity wounds of multiple etiologies across 644 institutions comparing a bioactive human skin allograft, TheraSkin, plus standard of care, to standard of care alone. Int Wound J 2020; 17 (01) 55-64
70 Marston WA, Hanft J, Norwood P, Pollak R. Dermagraft Diabetic Foot Ulcer Study Group. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care 2003; 26 (06) 1701-1705
71 Harding K, Sumner M, Cardinal M. A prospective, multicentre, randomised controlled study of human fibroblast-derived dermal substitute (Dermagraft) in patients with venous leg ulcers. Int Wound J 2013; 10 (02) 132-137
72 Gibbons GW. Grafix^®, a Cryopreserved Placental Membrane, for the Treatment of Chronic/Stalled Wounds. Adv Wound Care (New Rochelle) 2015; 4 (09) 534-544
73 Ananian CE, Davis RD, Johnson EL. et al. Wound Closure Outcomes Suggest Clinical Equivalency Between Lyopreserved and Cryopreserved Placental Membranes Containing Viable Cells. Adv Wound Care (New Rochelle) 2019; 8 (11) 546-554
74 Brantley JN, Verla TD. Use of placental membranes for the treatment of chronic diabetic foot ulcers. Adv Wound Care (New Rochelle) 2015; 4 (09) 545-559
75 Lavery LA, Fulmer J, Shebetka KA. et al; Grafix Diabetic Foot Ulcer Study Group. The efficacy and safety of Grafix(®) for the treatment of chronic diabetic foot ulcers: results of a multi-centre, controlled, randomised, blinded, clinical trial. Int Wound J 2014; 11 (05) 554-560
76 Raspovic KM, Wukich DK, Naiman DQ. et al. Effectiveness of viable cryopreserved placental membranes for management of diabetic foot ulcers in a real world setting. Wound Repair Regen 2018; 26 (02) 213-220
77 Barbul A, Gelly H, Masturzo A. The health economic impact of living cell tissue products in the treatment of chronic wounds: A retrospective analysis of medicare claims data. Adv Skin Wound Care 2020; 33 (01) 27-34
78 Carter MJ, Waycaster C, Schaum K, Gilligan AM. Cost-effectiveness of three adjunct cellular/tissue-derived products used in the management of chronic venous leg ulcers. Value Health 2014; 17 (08) 801-813
79 Floden EW, Malak SFF, Basil-Jones MM. et al. Biophysical characterization of ovine forestomach extracellular matrix biomaterials. J Biomed Mater Res B Appl Biomater 2011; 96 (01) 67-75
80 Raizman R, Hill R, Woo K. Prospectivemulticenter evaluation of an advanced extracellular matrix for wound management. Adv Skin Wound Care 2020; 33 (08) 437-444
81 Chen DW-C, Liu S-J. Nanofibers used for delivery of antimicrobial agents. Nanomedicine (Lond) 2015; 10 (12) 1959-1971
82 Ahmad T, McGrath S, Sirafim C. et al. Development of wound healing scaffolds with precisely-triggered sequential release of therapeutic nanoparticles. Biomater Sci 2020; (epub ahead of print)
83 Abaci HE, Guo Z, Coffman A. et al. Human skin constructs with spatially controlled vasculature using primary and iPSC-Derived Endothelial Cells. Adv Healthc Mater 2016; 5 (14) 1800-1807
84 Phua QH, Han HA, Soh B-S. Translational stem cell therapy: vascularized skin grafts in skin repair and regeneration. J Transl Med 2021; 19 (01) 83