Biomaterials used in cardiovascular prostheses suffer from well-known problems associated with surface-induced thrombosis and infection. These interfacial problems are major concerns that have remained unresolved and limited the success and applicability of existing biomedical polymers. The proposed studies will continue to focus on the preparation of new biomedical interface materials, through novel surface modification methodologies, designed to improve the host response to existing biomaterial implants. Specifically, interface materials will be used to investigate of the role of entropic repulsive hydration forces (ERF) on blood compatibility. The hypothesis that will be tested is that ERF represents a major determining factor in the adsorption, and the composition, organization and functional state of adsorbed plasma proteins, which then determines subsequent cell and molecular surface interactions. We propose to test the hypothesis on clinically-relevant biomaterials and controls, surface-modified with a series of interface materials that range from hydrophobic, to hydrophilic with increasing degree of hydration, prepared by radiofrequency plasma polymerization, to highly solvated oligosaccharides that will used to maximize ERF, prepared from novel oligosaccharide-hydrocarbon-oligosaccharide (OHO) triblock biopolymers that will be bound to test surfaces by strong hydrophobic interaction. Each surface modification will characterized by spectroscopic and physical methods, including atomic force microscopy (AFM) which will permit imaging at the submolecular level and examination of the intermolecular forces. The stability of the interface materials will be determined after exposure to water, buffer and SDS solution, under dynamic flow conditions. The effect of interfacial properties and ERF on plasma protein and platelet-surface interactions will be investigated in vitro by determining, under static and dynamic flow conditions, (l) the amount, composition, and functional integrity of key plasma proteins adsorbed from protein~solutions, media depleted of adhesive proteins, and human plasma; using radiolabel methods, infrared spectroscopy, immunolabel techniques employing Mab to adhesive proteins, and by submolecular AFM imaging of proteins; and (2) the amount and functional state of adsorbed platelets. From these studies, we shall attempt to determine the mechanism by which alteration in interfacial properties and ERF affects the adsorption and functional state of adhesive proteins, and how this correlates to blood compatibility. The proposed research, if successful, will lead to the development of important new classes of biomedical interface materials, that exhibit resistance to protein adsorption.
| Zhu, Junmin (2010) Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 31:4639-56 |
