Genetically Designed Materials for Cartilage Repair

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DESCRIPTION (provided by applicant): Biologically-based strategies for intervertebral disc repair or regeneration have been investigated including protein or gene delivery of growth factors or protease inhibitors, cell supplementation using stem, autologous cells or allogenic cells, and biomaterial supplementation including the use of in situ curing or cross-linking poly(vinyl) alcohols, poly(ethylene oxide), and poly(urethane)s. In this supplemental application, we propose to develop an in situ cross-linkable biologically-based material that may be bioinductive and act as a functional scaffold after implantation in the nucleus pulposus. In work ongoing on the parent grant, Genetically Designed Materials for Cartilage Repair", the laboratory has synthesized and evaluated an in situ cross-linkable elastin-based polypeptide useful for defect-filling applications in articular cartilage. The purpose of the proposed work is to develop modified versions of these polypeptides incorporating laminin peptide sequences that we believe may be appropriate for supporting intervertebral disc repair in mature or damaged tissues. This supplemental project will provide support for a one-year research experience for Dr. Lyman W. Whitlatch, a third-year neurosurgery resident. Dr. Whitlatch holds a Ph.D. in physiology and is interested in pursuing a career as a clinical investigator focused in spine upon completion of his residency. The proposed studies incorporate techniques of gene design, recombinant protein synthesis, biomaterial characterization, cell and molecular biology, biochemistry and histochemistry relevant to intervertebral disc biology. These studies will move Dr. Whitlatch towards his goal of developing a translational research program focused on the design and development of novel strategies for treatment of disc disorders.