Tissue engineering can be defined as the application of biological, chemical and engineering principles towards the development of biological substitutes for the repair or restoration of tissue function. This approach offers the possibility of replacing damaged or injured bone tissue with engineered constructs that can be used for guided bone regeneration. In this proposal, a tissue engineering approach will be investigated for the development of a novel, surface-modified, polymer system for use as an osteoinductive, biodegradable scaffold for the replacement of human bone grafts. This system involves the use of 2-dimensional (2-D), amino-acid alkyl ester containing polyphosphazenes (PPHOS) that will be surface modified by covalently attaching osteoinductive peptides to enhance the cellular responsiveness of osteoblasts and bone marrow derived stem cells. Covalently immobilized, osteoinductive peptides will be presented to cells on the surface of these polymeric scaffolds in efforts to enhance osteoblast cell differentiation and support new bone growth. Various tests will be performed to characterize the surface physico-chemical properties of the matrix as well as its in vitro osteoinductive properties and in vivo bone forming potential.
The specific aims of this proposal include: 1) Covalently immobilizing osteoinductive oligopeptide sequences to the surface of amino acid alkyl ester-containing PPHOS and characterizing their surface physico-chemical properties, 2) Characterizing the osteoinductive potential of and cellular responsiveness to surfacemodified PPHOS using in vitro techniques, and 3) Evaluating the biocompatibility and bone forming potential of surface-modified PPHOS using in vivo techniques.
