Skingineering

Abstract

Large full-thickness skin defects still represent a significant clinical problem for burn, plastic, and reconstructive surgeons. In fact, high morbidity and mortality in the acute phase, as well as functionally and cosmetically devastating scarring represent vexing problems that are far from being solved in a satisfactory way. Although a variety of biologic dressings and cultured skin substitutes, in particular cultured epithelial autografts, have contributed to improve short- and long-term outcomes of patients in the past, the authors hypothesize that only the bioengineering of near-natural autologous full-thickness skin grafts harbors the potential for a dimensional breakthrough. This review gives an insight into the development and characteristics of the autologous full-thickness skin grafts available for clinical application to date. In addition, recent scientific progress toward the bioengineering of dermoepidermal skin grafts which comprise a functional vasculature, pigmentation, neural elements, and skin appendages is discussed.

Keywords

bioengineered skin grafts - skin substitute - autologous skin graft

• References

• 1 Biedermann T, Boettcher-Haberzeth S, Reichmann E. Tissue engineering of skin for wound coverage. Eur J Pediatr Surg 2013; 23 (5) 375-382
• 2 Rheinwald JG, Green H. Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma. Cell 1975; 6 (3) 317-330
• 3 Meuli M, Raghunath M. Burns (Part 2). Tops and flops using cultured epithelial autografts in children. Pediatr Surg Int 1997; 12 (7) 471-477
• 4 Boyce S, Michel S, Reichert U, Shroot B, Schmidt R. Reconstructed skin from cultured human keratinocytes and fibroblasts on a collagen-glycosaminoglycan biopolymer substrate. Skin Pharmacol 1990; 3 (2) 136-143
• 5 Boyce ST. Cultured skin substitutes: a review. Tissue Eng 1996; 2 (4) 255-266
• 6 Boyce ST, Foreman TJ, English KB , et al. Skin wound closure in athymic mice with cultured human cells, biopolymers, and growth factors. Surgery 1991; 110 (5) 866-876
• 7 Barai ND, Boyce ST, Hoath SB, Visscher MO, Kasting GB. Improved barrier function observed in cultured skin substitutes developed under anchored conditions. Skin Res Technol 2008; 14 (4) 418-424
• 8 Barai ND, Supp AP, Kasting GB, Visscher MO, Boyce ST. Improvement of epidermal barrier properties in cultured skin substitutes after grafting onto athymic mice. Skin Pharmacol Physiol 2007; 20 (1) 21-28
• 9 Supp DM, Bell SM, Morgan JR, Boyce ST. Genetic modification of cultured skin substitutes by transduction of human keratinocytes and fibroblasts with platelet-derived growth factor-A. Wound Repair Regen 2000; 8 (1) 26-35
• 10 Supp DM, Wilson-Landy K, Boyce ST. Human dermal microvascular endothelial cells form vascular analogs in cultured skin substitutes after grafting to athymic mice. FASEB J 2002; 16 (8) 797-804
• 11 Supp DM, Boyce ST. Overexpression of vascular endothelial growth factor accelerates early vascularization and improves healing of genetically modified cultured skin substitutes. J Burn Care Rehabil 2002; 23 (1) 10-20
• 12 Supp DM, Supp AP, Bell SM, Boyce ST. Enhanced vascularization of cultured skin substitutes genetically modified to overexpress vascular endothelial growth factor. J Invest Dermatol 2000; 114 (1) 5-13
• 13 Kalyanaraman B, Boyce S. Assessment of an automated bioreactor to propagate and harvest keratinocytes for fabrication of engineered skin substitutes. Tissue Eng 2007; 13 (5) 983-993
• 14 Kalyanaraman B, Boyce ST. Wound healing on athymic mice with engineered skin substitutes fabricated with keratinocytes harvested from an automated bioreactor. J Surg Res 2009; 152 (2) 296-302
• 15 Powell HM, Boyce ST. EDC cross-linking improves skin substitute strength and stability. Biomaterials 2006; 27 (34) 5821-5827
• 16 Boyce ST, Kagan RJ, Yakuboff KP , et al. Cultured skin substitutes reduce donor skin harvesting for closure of excised, full-thickness burns. Ann Surg 2002; 235 (2) 269-279
• 17 Boyce ST, Kagan RJ, Greenhalgh DG , et al. Cultured skin substitutes reduce requirements for harvesting of skin autograft for closure of excised, full-thickness burns. J Trauma 2006; 60 (4) 821-829
• 18 Boyce ST, Goretsky MJ, Greenhalgh DG, Kagan RJ, Rieman MT, Warden GD. Comparative assessment of cultured skin substitutes and native skin autograft for treatment of full-thickness burns. Ann Surg 1995; 222 (6) 743-752
• 19 Passaretti D, Billmire D, Kagan R, Corcoran J, Boyce S. Autologous cultured skin substitutes conserve donor autograft in elective treatment of congenital giant melanocytic nevus. Plast Reconstr Surg 2004; 114 (6) 1523-1528
• 20 Braziulis E, Diezi M, Biedermann T , et al. Modified plastic compression of collagen hydrogels provides an ideal matrix for clinically applicable skin substitutes. Tissue Eng Part C Methods 2012; 18 (6) 464-474
• 21 Pontiggia L, Biedermann T, Meuli M , et al. Markers to evaluate the quality and self-renewing potential of engineered human skin substitutes in vitro and after transplantation. J Invest Dermatol 2009; 129 (2) 480-490
• 22 Braziulis E, Biedermann T, Hartmann-Fritsch F , et al. Skingineering I: engineering porcine dermo-epidermal skin analogues for autologous transplantation in a large animal model. Pediatr Surg Int 2011; 27 (3) 241-247
• 23 Schiestl C, Biedermann T, Braziulis E , et al. Skingineering II: transplantation of large-scale laboratory-grown skin analogues in a new pig model. Pediatr Surg Int 2011; 27 (3) 249-254
• 24 Biedermann T, Böttcher-Haberzeth S, Klar AS , et al. Rebuild, restore, reinnervate: do human tissue engineered dermo-epidermal skin analogs attract host nerve fibers for innervation?. Pediatr Surg Int 2013; 29 (1) 71-78
• 25 Biedermann T, Klar AS, Böttcher-Haberzeth S, Schiestl C, Reichmann E, Meuli M. Tissue-engineered dermo-epidermal skin analogs exhibit de novo formation of a near natural neurovascular link 10 weeks after transplantation. Pediatr Surg Int 2014; 30 (2) 165-172
• 26 Klar AS, Böttcher-Haberzeth S, Biedermann T, Schiestl C, Reichmann E, Meuli M. Analysis of blood and lymph vascularization patterns in tissue-engineered human dermo-epidermal skin analogs of different pigmentation. Pediatr Surg Int 2014; 30 (2) 223-231
• 27 Pontiggia L, Klar A, Böttcher-Haberzeth S, Biedermann T, Meuli M, Reichmann E. Optimizing in vitro culture conditions leads to a significantly shorter production time of human dermo-epidermal skin substitutes. Pediatr Surg Int 2013; 29 (3) 249-256
• 28 Hartmann-Fritsch F, Biedermann T, Braziulis E , et al. Collagen hydrogels strengthened by biodegradable meshes are a basis for dermo-epidermal skin grafts intended to reconstitute human skin in a one-step surgical intervention. J Tissue Eng Regen Med 2012;
• 29 Marino D, Luginbühl J, Scola S, Meuli M, Reichmann E. Bioengineering dermo-epidermal skin grafts with blood and lymphatic capillaries. Sci Transl Med 2014; 6 (221) 21ra14
• 30 Montaño I, Schiestl C, Schneider J , et al. Formation of human capillaries in vitro: the engineering of prevascularized matrices. Tissue Eng Part A 2010; 16 (1) 269-282
• 31 Klar AS, Güven S, Biedermann T , et al. Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells. Biomaterials 2014; 35 (19) 5065-5078
• 32 Sriwiriyanont P, Lynch KA, McFarland KL, Supp DM, Boyce ST. Characterization of hair follicle development in engineered skin substitutes. PLoS ONE 2013; 8 (6) e65664
• 33 Swope VB, Supp AP, Cornelius JR, Babcock GF, Boyce ST. Regulation of pigmentation in cultured skin substitutes by cytometric sorting of melanocytes and keratinocytes. J Invest Dermatol 1997; 109 (3) 289-295
• 34 Swope VB, Supp AP, Boyce ST. Regulation of cutaneous pigmentation by titration of human melanocytes in cultured skin substitutes grafted to athymic mice. Wound Repair Regen 2002; 10 (6) 378-386
• 35 Böttcher-Haberzeth S, Klar AS, Biedermann T , et al. “Trooping the color”: restoring the original donor skin color by addition of melanocytes to bioengineered skin analogs. Pediatr Surg Int 2013; 29 (3) 239-247
• 36 Biedermann T, Pontiggia L, Böttcher-Haberzeth S , et al. Human eccrine sweat gland cells can reconstitute a stratified epidermis. J Invest Dermatol 2010; 130 (8) 1996-2009
• 37 Pontiggia L, Biedermann T, Böttcher-Haberzeth S , et al. De novo epidermal regeneration using human eccrine sweat gland cells: higher competence of secretory over absorptive cells. J Invest Dermatol 2014; ; 10.1038/jid.2014.30
• 38 Böttcher-Haberzeth S, Biedermann T, Pontiggia L , et al. Human eccrine sweat gland cells turn into melanin-uptaking keratinocytes in dermo-epidermal skin substitutes. J Invest Dermatol 2013; 133 (2) 316-324
• 39 Hartmann-Fritsch F, Hosper N, Luginbühl J, Biedermann T, Reichmann E, Meuli M. Human amniotic fluid derived cells can competently substitute dermal fibroblasts in a tissue-engineered dermo-epidermal skin analog. Pediatr Surg Int 2013; 29 (1) 61-69
• 40 Böttcher-Haberzeth S, Biedermann T, Klar AS , et al. Tissue engineering of skin: human tonsil-derived mesenchymal cells can function as dermal fibroblasts. Pediatr Surg Int 2014; 30 (2) 213-222
• 41 Natesan S, Wrice NL, Baer DG, Christy RJ. Debrided skin as a source of autologous stem cells for wound repair. Stem Cells 2011; 29 (8) 1219-1230
• 42 Natesan S, Zamora DO, Wrice NL, Baer DG, Christy RJ. Bilayer hydrogel with autologous stem cells derived from debrided human burn skin for improved skin regeneration. J Burn Care Res 2013; 34 (1) 18-30