CHME - Bioseparations Biomaterials Group Project C

Project C

Development of biomimetic endothelial surfaces
My research focus is to develop an in-depth understanding of the mechanisms involved in blood-biomaterial interactions and addresses the hypothesis that the hemocompatibility of biomaterials is at least in part dependent on the adsorption and activation of specific plasma proteins. Both EPCR and hTM are components of the endothelium that control and regulate the thrombotic events on the native endothelium (schematically shown in Figure 1).

My interest is in the preparation of surfaces that mimic the anticoagulant components of the native endothelium. While biomedical grade polyurethane (PU) has been surface modified to enable the covalent immobilization of proteins, my laboratory has designed a novel methodology (a patent non-disclosure has been filed) to surface modify PU by grafting a “Y-shaped fork” on the PU backbone that affords the sequential and directed immobilization of two proteins (Figure 2).

Project C Diagram
Figure 1: Model for protein-C activation on the native endothelium. In the absence of EPCR (panel-A), protein-c activation is mediated by thrombin-TM complex is a low affinity reaction. The high affinity binding of EPCR to protein-C on the endothelial cell surface is critical for activation (panel-B). After binding to EPCR, the structure of protein-C is modulated to enable rapid conversion to active form.
Project C Diagram
Figure 2: Surface modification of PU. Biomedical grade PU was surface modified to enable the grafting of a bi-dentate functionality (“Y”) which allows for the addition of proteins via coupling or nucleophilic reactions. Specifically, EPCR and TM were immobilized to mimic the catalytic reaction of panel-B in figure-3.
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