Synthesis & Application of Biocompatible Polymers for Sensors

A layer-by-layer (LbL) assembly is proposed herein to develop polymeric coatings with immobilized organoselenium (RSe) moieties that can be utilized to improve the biocompatibility of blood contacting medical devices and also to prepare amperometric blood S-nitrosothiol (RSNO) sensors. The coatings will be capable of locally generating nitric oxide (NO), a potent antiplatelet agent (to prevent thrombosis), from endogenous S- nitrosothiol species present in blood. Key aims for this project are to: 1) synthesize NO generating LbLs by covalently coupling catalytic organoselenium species to a variety of polycations (e.g. polyethyleneimine, polylysine, and chitosan etc.) and alternately expose the surface of biomedical grade polymer substrates to these polycationic species and also an appropriate polyanion (e.g., alginate, heparin, etc.) to build up a large number of bilayer polyelectrolyte layers; 2) test, in vitro, the ability of these assemblies to generate NO catalytically using different endogenous RSNOs species present at normal blood levels and further assess their robustness against RSe catalyst leaching; 3) examine the efficacy of these LbL coatings to reduce thrombus formation in vivo and for their toxicity, pyrogenic and, inflammatory affects; and 4) utilize the new catalytic LbL coatings to devise various sensor designs for measurement of RSNOs in fresh blood. The feasibility of proposed chemistry is anticipated to be high because of the substantial preliminary in vitro results already obtained by Professor Meyerhoff`s laboratory at the University of Michigan using RSe species to generate NO from RSNOs. The proposed project will help in further understanding and refining the LbL coating chemistries, optimizing the synthesis process, and determining whether the amount of NO generated will have the expected inhibitory effect on thrombus formation as well as platelet activation and adhesion in vivo. The research is very significant owing to the continuing biocompatibility problemshrombotic risk associated with a wide range of implantable biomedical devices. The new LbL coatings can potentially solve these problems. Further, the development of new RSNO sensors for rapid whole blood measurement using the same LbL catalytic coatings could provide a new diagnostic tool that can be used to assess endothelial function in patients (and associated risk for heart attacks and strokes), as well as detect the early onset of sepsis in critically ill hospital patients.