The long term objective of this research program is to develop a new class of materials, elastomeric polypeptide biomaterials, for use as vascular prostheses.
The specific aims are: 1) to design polypeptide elastomers which match the compliance of the small vessels to be replaced, 2) to identify and suitably incorporate chemotactic peptides for vascular endothelial and smooth muscle cells, 3) to identify and covalently incorporate cell attachment sequences for vascular endothelial and smooth muscle cells into the elastomeric vascular prosthesis and 4) to achieve this within a biocompatible and appropriately biodegradable elastomeric matrix. The basic elastomeric polypeptide is (Val-Pro-Gly-Val-Gly)n or simply (VPGVG)n. For the bulk of the synthetic vessel the repeating hexapeptide, (Val-Ala-Pro-Gly-Val-Gly)n or simply (VAPGVG)n, will be added to modulate elastic modulus and to give strength and satisfactory handling characeristics. The general formula will be ((VPGVG)m-(VAPGVG)n) with molecular weights of greater and 50,000 Daltons. Cell attachment sequences for vascular endothelial and smooth muscle cells will be incorporated within the polypentapeptide at appropriate ratio of cell attachment sequence to pentamer sequence. Chemotactic peptides will be included in such a way as to provide the requisite concentration gradient for chemotaxis. The experimental design and methods involve four major categories: 1) design and preparation of elastomeric matrices by means of peptide synthesis of multicomponent high polymers and gamma-irradiation cross-linking with the capability of making cell specific vessel wall layering, 2) physical characterization of the synthetic high polymers by spectroscopic, compositional and relaxational analyses and of the cross-linked matrices by means of mechanical studies, primarily stress/strain for determination of elastic modulus, hysteresis and fatiguing and temparature dependence of force at fixed length and of length fixed force, 3) chemotaxis and cell adhesion studies on vascular endothelial and smooth muscle cells involving standard assays and the prepared matrices, and 4) additional site specific interactions for vascular prostheses including assessment of calcification potential, assessment of in vivo thromboembolic potential (by collaboration) and biocompatibility and in vivo biodegradability (by collaboration). Animal implant studies to assess rate of cell migration into the material, rate of matrix component synthesis by the cells, rate of degradative removal of synthetic matrix, etc., will be pursued by means of collaboration once adequate perspective is obtained regarding on going development of the material and which elements a given collaborator would determine.
| Nicol, A; Gowda, D C; Urry, D W (1992) Cell adhesion and growth on synthetic elastomeric matrices containing Arg-Gly-Asp-Ser-3. J Biomed Mater Res 26:393-413 |
