Cellular Engineering: Bioengineering of the skin Skin substitutes from cultured cells and collagen-GAG polymers

Engineering skin substitutes provides a potential source of advanced therapies for the treatment of acute and chronic wounds. Cultured skin substitutes (CSS) consisting of human keratinocytes and fibroblasts attached to collagen-glycosaminoglycan substrates have been designed and tested in preclinical and clinical studies. Cell culture techniques follow general principles of primary culture and cryopreservation in liquid nitrogen for longterm storage. Biopolymer substrates are fabricated from xenogeneic (bovine) collagen and glycosaminoglycan that are Iyophilised for storage until use. At maturity in air-exposed culture, CSS develop an epidermal barrier that is not statistically different from native human skin, as measured by surface electrical capacitance. Preclinical studies in athymic mice show rapid healing, expression of cytokines and regulation of pigmentation. Clinical studies in burn patients demonstrate a qualitative outcome with autologous skin that is not different from 1 : 4 meshed, split-thickness autograft skin, and with a quantitative advantage over autograft skin in the ratio of healed skin to biopsy areas. Chronic wounds resulting from diabetes or venous stasis have been closed successfully with allogeneic CSS prepared from cryopreserved skin cells. These results define the therapeutic benefits of cultured skin substitutes prepared with skin cells from the patient or from cadaver donors. Future directions include genetic modification of transplanted cells to improve wound healing transiently or to deliver gene products systemically. Keywords-Cultured skin substitutes, Wound healing, Keratinocytes, Fibroblasts, Biopolymers Med. BioI. Eng. Comput., 1998,36,791-800 November 1998 1 Objectives ENGINEERINGSKIN substitutes provides a potential source of advanced therapies for the treatment of acute and chronic skin wounds. Hypothetically, the engineering of skin substitutes can allow deliberate fabrication of biological materials with properties that address specific patho-biological conditions (e.g. burns, scars, cutaneous ulcers, congenital anomalies). Through the design and incorporation of specific therapeutic properties in skin substitutes, reduction in morbidity and mortality from full-thickness skin wounds may be facilitated. Morbidity from the grafting of autologous, split-thickness skin (ROBSONet a!., 1992) occurs at both the treatment site and the donor site (McHUGH et a!., 1997). Acute wounds that require grafting include excised burns, burn scars and congenital cutaneous anomalies (giant naevus). Patients with acute wounds, in general, do not have healing impairment, but may not have sufficient donor sites to cover their wounds if large total body surface areas (TBSAs) are involved. Estimates for hospitalisations from burns range from 60000 to 80000 annually, and costs for recovery from acute injuries Correspondence should be addressed to Dr S T Boyce; email: [email protected] First received 4 November 1997 and in final form 23 March 1998