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Review
. 2018 Jan 24:6:4.
doi: 10.1186/s41038-017-0103-y. eCollection 2018.

Tissue engineering of skin and regenerative medicine for wound care

Steven T Boyce  1   2 , Andrea L Lalley  2
Affiliations
Review

Tissue engineering of skin and regenerative medicine for wound care

Steven T Boyce et al. Burns Trauma. .

Abstract

Engineering of biologic skin substitutes has progressed over time from individual applications of skin cells, or biopolymer scaffolds, to combinations of cells and scaffolds for treatment, healing, and closure of acute and chronic skin wounds. Skin substitutes may be categorized into three groups: acellular scaffolds, temporary substitutes containing allogeneic skin cells, and permanent substitutes containing autologous skin cells. Combined use of acellular dermal substitutes with permanent skin substitutes containing autologous cells has been shown to provide definitive wound closure in burns involving greater than 90% of the total body surface area. These advances have contributed to reduced morbidity and mortality from both acute and chronic wounds but, to date, have failed to replace all of the structures and functions of the skin. Among the remaining deficiencies in cellular or biologic skin substitutes are hypopigmentation, absence of stable vascular and lymphatic networks, absence of hair follicles, sebaceous and sweat glands, and incomplete innervation. Correction of these deficiencies depends on regulation of biologic pathways of embryonic and fetal development to restore the full anatomy and physiology of uninjured skin. Elucidation and integration of developmental biology into future models of biologic skin substitutes promises to restore complete anatomy and physiology, and further reduce morbidity from skin wounds and scar. This article offers a review of recent advances in skin cell thrapies and discusses the future prospects in cutaneous regeneration.

Keywords: Burns; Cell therapy; Regenerative medicine; Scar; Skin substitute; Tissue engineering; Wound closure.

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Conflict of interest statement

All human subject research was performed with approval of the University of Cincinnati Institutional Review Board with regulatory oversight by the US Food and Drug Administration. All animal subject research was performed with approval of the University of Cincinnati Institutional Animal Care and Use Committee and the Animal Care and Use Research Office of the US Army Medical Research and Materiel Command.An informed consent to publish de-identified data was obtained from the subjects.The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Clinical application of autologous engineered skin substitutes (ESS). a Histology of ESS shows a collagen-based polymer scaffold populated with cultured dermal fibroblasts and epidermal keratinocytes. Scale bar = 0.1 mm. b Surgical application of ESS on prepared wounds can be performed using forceps and secured with staples. c An African-American subject treated with ESS at 3 years of age shows predominant hypopigmentation. d The same subject at 14 years of age has persistent hypopigmentation but has required no reconstruction of the ESS site. Scales in centimeters
Fig. 2
Fig. 2
Correction of pigmentation with cultured autologous melanocytes in preclinical studies. a Human engineered skin substitutes (ESS) on immunodeficient mice showing hypopigmentation at 12 weeks after grafting. b Correction of hypopigmentation after 12 weeks by addition of isogeneic human melanocytes to ESS. Scales in centimeters. c Immunolabeling of epidermis with anti-cytokeratin (red) and the melanocyte-specific maker, tyrosinase-related protein-1 (TRP-1; negative). d Immunolabeling of ESS with added melanocytes shows epidermis (red), and TRP-1-positive melanocytes at the dermal-epidermal junction (white arrows) as in uninjured skin. Scale bars = 50 μm
Fig. 3
Fig. 3
Induction of hair follicles in vivo from neonatal dermal cells grafted to immunodeficient mice. a Human dermal fibroblasts and human epidermal keratinocytes express no hair. b Neonatal murine fibroblasts and human neonatal keratinocytes express chimeric hair at 4 weeks after grafting. Scales in cm. c Higher magnification showing density of regenerated hair is similar to that on positive control mice. Scale = 1 mm
See this image and copyright information in PMC

References

    1. Finnerty CC, Capek K, Voigt C, Hundeshagen G, Cambiaso-Daniel J, Porter C, Sousse LE, El Ayadi A, Zapata-Sirvent R, Guillory A, et al. The P50 research center in perioperative sciences: how the investment by the National Institute of General Medical Sciences in Team Science has reduced post-burn mortality. J Trauma Acute Care Surg. 2017;83(3):532–542. doi: 10.1097/TA.0000000000001644. - DOI - PMC - PubMed
    1. Warden GD, Saffle JR, Kravitz M. A two-stage technique for excision and grafting of burn wounds. J Trauma. 1982;22(2):98–103. doi: 10.1097/00005373-198202000-00004. - DOI - PubMed
    1. Wood FM, Giles N, Stevenson A, Rea S, Fear M. Characterisation of the cell suspension harvested from the dermal epidermal junction using a ReCell(R) kit. Burns. 2012;38(1):44–51. doi: 10.1016/j.burns.2011.03.001. - DOI - PubMed
    1. Green H, Kehinde O, Thomas J. Growth of human epidermal cells into multiple epithelia suitable for grafting. Proc Natl Acad Sci U S A. 1979;76:5665–5668. doi: 10.1073/pnas.76.11.5665. - DOI - PMC - PubMed
    1. Boyce ST, Hansbrough JF. Biologic attachment, growth, and differentiation of cultured human epidermal keratinocytes on a graftable collagen and chondroitin-6-sulfate substrate. Surgery. 1988;103:421–431. - PubMed