Abstract

The skin equivalent serves as a model of skin that will be used to gain a better understanding of the basic mechanisms of graft rejection and to amplify skin in vitro for the treatment of burn victims. The skin equivalent is constructed by adding a suspension of epidermal cells to the surface of a collagen lattice formed by combining fibroblasts with type I collagen, serum, and tissue culture medium. Two strains of mice, DBA/2J mice which carry the H-2d haplotype, and CBA/J mice which carry the H-2k haplotype, will be used to examine the role of fibroblasts and keratinocytes in provoking an immune response. Skin equivalents that contain isogeneic fibroblasts and keratinocytes, allogeneic fibroblasts and isogeneic keratinocytes, isogeneic fibroblasts and allogeneic keratinocytes, or allogeneic fibroblasts and keratinocytes will be grafted to CBA/2J mice. Grafts will be removed at time intervals ranging from five days to two months after surgery and frozen for cryosectioning followed by staining with antibodies to the surface antigens of B cells, T helper cells, T suppressor cells, and T suppressor-cytotoxic cells. The time course and relative number of inflammatory cells per square micrometer will be compared among the four types of grafts to differentiate between the role of allogeneic fibroblasts and allogeneic keratinocytes in graft rejection. Concurrent studies with patients at the Regional Burn Center at Miami Valley Hospital will be carried out to determine whether skin equivalents containing allogeneic fibroblasts and a patient's own epidermal cells provides a viable method for expanding the surface area of skin which can be covered from the limited skin available in an extensively burned individual. The main focus of the clinical phase of this project will be the construction and application of lattices that approach the size of conventional meshed graphs. To demonstrate the clinical usefulness of the skin equivalent, it will also be necessary to document histologically the integration and long-term fate of the grafts.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR039297-01
Application #
3159308
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Wright State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Dayton
State
OH
Country
United States
Zip Code
45435