Multimodal, Biomaterial-Focused Anticoagulation via Superlow Fouling Zwitterionic Functional Groups Coupled with Anti-Platelet Nitric Oxide Release

The functions of anti-fouling, zwitterionic polycarboxybetaine (pCB) coating, and anti-platelet nitric oxide (NO) release replicate key anticoagulant properties of the endothelium. The two approaches, only tested separately thus far, are paired on gas permeable polydimethylsiloxane (PDMS) membranes and evaluated for fibrinogen (Fg) and platelet adsorption. Uncoated (control) and pCB-coated PDMS separate sheep plasma (10(8) platelets per milliliter) and gas flow chambers within bioreactors used in this study, and either 100 or 0 ppm of NO/N-2 flows through the gas chamber so PDMS transfers NO into flowing plasma. Surface-adsorbed platelets are quantified using a lactate dehydrogenase assay after 8h plasma recirculation. Fg and platelet adsorption on pCB-coated PDMS are 10.40% +/- 3.0% of control (p < 0.01) and 23.3% +/- 7.4% (p < 0.01) of control, respectively. NO flux alone limits platelet adsorption to 79.0% +/- 5.0% (p < 0.05) of control. Together, NO and pCB reduce platelet adsorption to 6.90% +/- 1.30% of control (p < 0.001). The data suggest that pCB coating and NO act in concert to reduce platelet fouling at significantly higher levels than either pCB coating or NO release alone.