? Current biomaterials suffer from well-known problems including thrombosis, excessive wound healing, and infection. The surface, or interface, of a biomaterial is one of the most important factors that determine these host responses. The proposed studies focus on new biomimetic interface materials designed to improve host responses to biomaterials, and are based on the central hypothesis that controlled spatial placement of oligosaccharides and/or cell adhesion peptides on a biomaterial will facilitate programmed biological responses that minimize non-specific interactions, and enhance selective cell-surface interaction and shear stable surface endothelialization. Proposed research will be focused through two operational paradigms, 'cell surface glycocalyx' and 'extracellular matrix' (ECM), that provide guidance in biomimetic designs and focus specific research on: (1) Biomimetic materials that mimic the non-adhesive properties and anticoagulant function of a glycocalyx, designed to improve blood compatibility; and (2) biomimetic materials that mimic adhesive glycoproteins in the ECM designed to facilitate shear stable endothelialization. The biomimetic materials undergo surface-induced assembly on a range of clinically relevant biomaterials, and consist of surfactant polymers with pendant oligosaccharides, peptides, and hydrophobic ligands. The oligosaccharides include glycodendrimers and bottle-brush constructs that will provide a dense glycocalyx-like interface. ECM-like biomimetic materials incorporate high affinity integrin binding and heparin proteoglycan binding peptides, characterized by spectroscopic and microscopic techniques including methods to assist in the quantification of surface ligand densities and nanoscale imaging of surface assemblies. In vitro blood compatibility will be determined from spectroscopic, microscopic, and labeling measurements under well defined flow conditions. Endothelial cell studies will include shear-dependent analysis of actin stress fibers and focal adhesion proteins using confocal microscopy. Blood compatibility also will be determined using a well-established porcine a-v shunt model. From these studies, we shall determine the mechanisms by which alterations in the biomimetic interface correlates to blood compatibility and shear stable endothelialization. ? ?
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