The objective of the proposed research is to develop a living replacement of skin that can be used in the treatment of major burns and skin losses. New methods have recently been developed in the laboratory of one of the co-investigators for convenient and rapid growth in defined medium of human epidermal keratinocytes, and for control of keratinocyte differentiation in culture. In addition, a slowly biodegradable synthetic dermal membrane composed of crosslinked collagen and glycosaminoglycans has recently been described in the literature for use in treating major burns. The overall research plan is to establish cultures of epidermal keratinocytes from a small skin biopsy, expand the cells in culture, coat the membrane with cultured keratinocytes, induce stratification of the keratinocytes and terminal differentiation of the outer layer, and then use the living artificial skin that has been generated for grafting. The cultures will be carefully monitored at all stages to verify absence of malignant transformation and undesirable antigenic changes. An interdisciplinary research team of basic scientists and physicians has been assembled with all of the needed expertise in cell culture, dermatology, biochemistry, oncology and clinical management of burns needed for this project. We anticipate that this procedure will allow cells from a small amount of a burn patient's unburned skin to be expanded rapidly in number and used to prepare a graft that can then be placed permanently over a large burned area with minimum risk of rejection. Such a procedure should greatly reduce total treatment time for patients with burns over a large area of the body, reduce the amount of donor tissue required for grafting, and increase the chances of saving very severely burned patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM035068-01
Application #
3287118
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1985-02-01
Project End
1988-01-31
Budget Start
1985-02-01
Budget End
1986-01-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Boyce, S T; Stompro, B E; Hansbrough, J F (1992) Biotinylation of implantable collagen for drug delivery. J Biomed Mater Res 26:547-53
Boyce, S T; Foreman, T J; Furmanski, P et al. (1992) Absence of tumorigenicity in athymic mice by normal human epidermal keratinocytes after culture in serum-free medium. Cancer Lett 62:141-7
Cooper, M L; Spielvogel, R L; Hansbrough, J F et al. (1991) Reconstitution of the histologic characteristics of a giant congenital nevomelanocytic nevus employing the athymic mouse and a cultured skin substitute. J Invest Dermatol 97:649-58
Boyce, S T; Foreman, T J; English, K B et al. (1991) Skin wound closure in athymic mice with cultured human cells, biopolymers, and growth factors. Surgery 110:866-76
Cooper, M L; Hansbrough, J F (1991) Use of a composite skin graft composed of cultured human keratinocytes and fibroblasts and a collagen-GAG matrix to cover full-thickness wounds on athymic mice. Surgery 109:198-207
Hansbrough, J F; Boyce, S T; Cooper, M L et al. (1989) Burn wound closure with cultured autologous keratinocytes and fibroblasts attached to a collagen-glycosaminoglycan substrate. JAMA 262:2125-30
Stompro, B E; Hansbrough, J F; Boyce, S T (1989) Attachment of peptide growth factors to implantable collagen. J Surg Res 46:413-21
Boyce, S T; Glafkides, M C; Foreman, T J et al. (1988) Reduced wound contraction after grafting of full-thickness burns with a collagen and chondroitin-6-sulfate (GAG) dermal skin substitute and coverage with biobrane. J Burn Care Rehabil 9:364-70
Boyce, S T; Hansbrough, J F (1988) Biologic attachment, growth, and differentiation of cultured human epidermal keratinocytes on a graftable collagen and chondroitin-6-sulfate substrate. Surgery 103:421-31
Boyce, S T; Christianson, D J; Hansbrough, J F (1988) Structure of a collagen-GAG dermal skin substitute optimized for cultured human epidermal keratinocytes. J Biomed Mater Res 22:939-57

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