Skin tissue engineering advances in severe burns: review and therapeutic applications

Abstract

Current advances in basic stem cell research and tissue engineering augur well for the development of improved cultured skin tissue substitutes: a class of products that is still fraught with limitations for clinical use. Although the ability to grow autologous keratinocytes in-vitro from a small skin biopsy into sheets of stratified epithelium (within 3 to 4 weeks) helped alleviate the problem of insufficient donor site for extensive burn, many burn units still have to grapple with insufficient skin allografts which are used as intermediate wound coverage after burn excision. Alternatives offered by tissue-engineered skin dermal replacements to meet emergency demand have been used fairly successfully. Despite the availability of these commercial products, they all suffer from the same problems of extremely high cost, sub-normal skin microstructure and inconsistent engraftment, especially in full thickness burns. Clinical practice for severe burn treatment has since evolved to incorporate these tissue-engineered skin substitutes, usually as an adjunct to speed up epithelization for wound closure and/or to improve quality of life by improving the functional and cosmetic results long-term. This review seeks to bring the reader through the beginnings of skin tissue engineering, the utilization of some of the key products developed for the treatment of severe burns and the hope of harnessing stem cells to improve on current practice.

Keywords: Burns; Cultured epithelial autografts; Dermal substitutes; Microskin grafting; Skin tissue engineering; Stem cells.

Fig. 1

Timeline of skin tissue engineering in burn surgery

Fig. 2

Cultured epithelial autograft supported on a fibrin mat [38] used at the Singapore General Hospital Burns Centre to treat major burns

Fig. 3

Grafting of cultured epithelial autografts on allodermis at Singapore General Hospital Burns Centre based on Cuono’s two-stage method

Fig. 4

Colony forming efficiency assay: a simple way of measuring the clonogenic ability of keratinocytes and estimating the growth capacity of these cells

Fig. 5

Application of Biobrane. a. Before application b. After application

Fig. 6

Combining cultured epithelial autografts and widely-meshed autografts

Fig. 7

Microskin autografting on an extensive-burn patient at the Singapore General Hospital Burns Centre. a. Split thickness skin autografts were cut into small pieces and laid in close proximity with one another on cadaveric allografts. b. Sheets of autologous microskin-allografts were grafted onto recipient wound bed