SBIR-STTR Award

The goal of this proposal is to optimize the barrier function properties of a human skin equivalent culture for eventual commercialization as an in vitro test for chemicals and formulations. Human skin equivalent assays are the best alternative to animal testing for evaluating the effect of chemicals on the barrier properties of human skin. Such tests are needed to prevent the inclusion of ingredients in consumer products, cosmetics or topically applied pharmaceuticals that would damage this critical function of skin. The tests also are needed to discover new ways of safely disrupting barrier function for the transdermal delivery of new pharmaceuticals. The skin equivalent cultures currently available have much poorer barrier function properties than human skin and are therefore inadequate for testing barrier function. The proposal will utilize a new and proprietary human skin cell line called NIKS(TM) (normal immortalized keratinocytes). NIKS(TM) cells can establish fully differentiated organotypic cultures of human skin. In contrast to primary keratinocytes, the immortalized NIKS(TM) cells can be used to establish genetically altered cell lines. The present studies will use this novel property of NIKS(TM) cells, as well as optimization of the culture conditions, to generate skin equivalent cultures with improved barrier function. PROPOSED COMMERCIAL APPLICATION: The goal of these studies is to provide a commercial skin substitute for in vitro pharmacological and toxicological testing assays that has barrier function comparable to that of normal skin. Cosmetic companies spend approximately $50 million to $100 million per year on safety testing new compounds and formulations on animal or human skin. Household product and pharmaceutical companies make similar expenditures. Current skin substitutes are significantly defective in barrier function. These industries need a simple assay system that mimics the barrier properties of human skin. Stratatech is developing products and contract services for this large market using its proprietary skin cell line

Severe burns and other major trauma to the skin are life-threatening injuries that often require immediate surgical intervention. Typically, this involves temporary coverage of the wound site with cadaver skin or synthetic dressings to prevent infection and dehydration. Permanent closure of the wound is generally accomplished through split-thickness skin autografting after the wound bed has healed to the point that it will accept autograft tissue. Although this regimen is the standard of care for severe skin wounds, limited availability of cadaver skin, the potential for transmission of pathogens from donor tissue, and the ultimate rejection of the cadaver skin pose serious drawbacks to this approach. Safe and effective alternatives to the use of cadaver skin are needed to improve the care of patients with these life-threatening wounds. Stratatech Corporation has developed a novel cultured skin substitute tissue, StrataGraft(tm) skin tissue, for the temporary management of severe skin wounds prior to autografting. The development and optimization of StrataGraft(tm) tissue was funded in part by the Phase I portion of this SBIR project. StrataGraft(tm) tissue is a living combination skin substitute with a fully-stratified epidermal layer which imparts permeability barrier function comparable to that of native epidermis. The FDA has approved a Phase I/II clinical trial (IND#10113) for Stratatech to evaluate the safety and efficacy of StrataGraft(tm) skin tissue as an alternative to cadaver skin in the temporary management of severe skin defects requiring surgical intervention. This Phase II SBIR proposal is designed to build on the success of the Phase I project by performing a clinical evaluation of StrataGraft(tm) skin tissue. Successful completion of this Phase l/ll clinical trial will position Stratatech to conduct a pivotal Phase III clinical trial, leading to the ultimate commercialization of StrataGraft(tm) skin tissue as an improved therapy for the management of burns and other severe skin trauma