Biocompatible polymer interactions with biological structures

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We recently described a universal glue' for cells based on our surprising observation that hyperbranched or linear polymers decorated with zwitterionic choline-phosphate (CP) groups bound strongly to cell membranes containing PC groups, which are ubiquitous in nature. This discovery should lead to numerous biomedical applications, for instance in blood arrest and tissue sealing (hemostasis) during surgery, but the field is evolving slowly because of low efficiencies in synthesizing CP groups. Our long term goal is to develop a new category of hemostatic materials based on this or related types of bioadhesion that would attach to tissue margins and induce plugging by aggregating blood cells. In the near term we will synthesize a family of hyperbranched polyglycerols (HPGs) carrying related betaines, known in all but the CP case to be repulsive to proteins and cells, with and without added polycations to provide adhesive energy for cell binding. The goal here is (a) to better understand the anomaly of CP binding to cells but rejecting proteins, and (b) to develop new bioadhesives based on betaine protection against normally damaging polycation-induced binding. We have recently studied such a polymer system in blood and have found complex coagulation responses, for instance, with the polymers binding to red cells and platelets causing activation and aggregation while inhibiting parts of the coagulation cascade and clot formation. We plan to greatly expand such studies in the next funding period to be able to better tailor the biological response to polymers bearing these groups.