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| Steven T Boyce, B.A., Ph.D., |
Professor; Director, Skin Substitute Laboratories, Shriners Hospitals for Children - Cincinnati
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513-872-6080
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Areas of Specialization - Medical benefits from improved healing may include, but not be limited to; reducedrequirements for split-thickness skin autograft, shorter hospitalizationtime, and reduced long-term debilitation after recovery. However, anatomicand physiologic deficiencies of all current models of cultured skin haverestricted realization of these benefits. Major deficiencies result fromculture conditions that do not produce an epidermal analogue with truebarrier properties, and from absence of a vascular plexus in dermalanalogues. The current model of cultured skin in this laboratory is acollagen-based sponge populated with cultured human keratinocytes andfibroblasts. Proposed studies will address and correct some or all of thedeficiencies of cultured skin by integrated studies in vitro, in animals, and in burn patients. In vitro studies will address: a media eg; nutrient, mitogen and biophysical conditions that affect cellularmetabolism of keratinocytes, fibroblasts, and melanocytes; b compositionstructure and biochemistry of implantable biopolymer substrates for celldelivery; and c expression of cytokines and adhesion proteins by skinanalogues before grafting. Evaluation of these factors will be performedby: a measurements of cell growth DNA synthesis and epidermaldifferentiation barrier ultrastructure, lipids, trans epidermal waterloss, surface hydrophobicity; b electron microscopy and biochemicalassay of biopolymer substrates; and c western blot analyses of expressedcytokines and adhesion proteins. Skin analogues withoptimal compositionwill be compared to controls human xenograft, autograft, no graft forefficacy wound contraction, HLA-ABC expression, skin pigmentationmelanin content, tyrosinase and expression of cytokines and adhesionproteins by grafting to full-thickness skin wounds on athymic mice. Experimental wounds will also be treated to stimulate vascularizationduring initial engraftment by topical delivery of angiogenic agents bFGF, TGF-beta, and nutrients to improve cell survival. Angiogenesis will bestudiedversus time after grafting by: a acrylic casts of the neovascularplexus; b transcutaneous oxygen; and c laser Doppler of capillary bloodflow. Clinical studies will focus on stimulation of angiogenesis, andcontrol of microbial contamination of the skin substitute duringengraftment. Excised burns treated with composite cultured skin will bestudied in the clinic by paired-site comparison to treatment with meshedsplit-thickness skin autograft. Comparative parameters of outcome willinclude: a engraftment of cultured skin incidence of failure, degree ofinfection, time to wound closure, need for reconstruction; and b long- term results function, contraction and cosmesis. The investigatorspossess all of required expertise in cell biology, skin biochemistry andbiophysics, wound physiology, and clinical burn care to perform thesestudies successfully. Accomplishment of these objectives may contribute toreduced mortality and morbidity from burns, improved materials for plasticand reconstructive surgery, validated models as alternatives to animaltesting of consumer products, and development of other tissue and organsubstitutes.
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