CELL ADHESION AND FUNCTIONS OF BIOSPECIFIC POLYMERS

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Advanced design of biomaterials can control and manipulate the behavior of a distinct type of cell in modulating specific physiological functions for the potential treatment of various clinical problems. It is hypothesized that the grafted peptides on the poly(ethylene glycol)-diacrylate (PEGDA) network can mediate the adhesion of a specific cell type with unaltered potential functions. Four specific aims are formulated. First, the PEGDA network will be synthesized and the physicochemical properties will be characterized. Secondly, biospecific adhesion peptides will be grafted onto the polymer network. These ligands include GREDVY for endothelial cells, FKYxAxALdAR for phagocytic Ieukocytes, GYIGSRY for multiple cell types including flbroblasts, and RDEV, YISGR, and no grafting will be used as negative controls. Radiolabeled peptides will be used to ascertain the surface composition and density of grafted peptides with radiodetection. Thirdly, the grafted network will be incubated with endothelial cells, phagocytic leukocytes, or fibroblasts for various durations. Adhesion, viability, and proliferation will be monitored and quantified. Peptide and cell ligand specificity will be assessed by incubation with monoclonal antibodies and by incubating cells with free peptides prior to the adhesion assay. Lastly, the characteristic functions of each adherent cell type will be determined after various external challenges in vitro. These functional assays include (a) VEGF release, Factor VIII expression, and E-selectin expression for the adhesion and proliferation of endothelial cells, (b) superoxide, myeloperoxidase, interieukin-1, and C3 production by leukocytes, and (c) proliferation of flbrobIasts. The effects of adherent monocytes/macrophages in mediating the inflammatory response in vivo will be investigated further by using the cage-implant animal model.