Multi-Modal, Surface-Focused Anticoagulation Using Poly-2-methoxyethylacrylate Polymer Grafts and Surface Nitric Oxide Release

This study examines platelet adhesion on surfaces that combine coatings to limit protein adsorption along with anti-platelet nitric oxide (NO) release. Uncoated and poly-2-methoxyethylacrylate (PMEA) coated, gas permeable polypropylene (PP) membranes were placed in a bioreactor to separate plasma and gas flows. Nitrogen with 100/500/1000 ppm of NO was supplied to the gas side as a proof of concept. On the plasma side, platelet rich plasma (PRP, 1 x 108 cell/mL) was recirculated at low (60)/high (300) flows (mL/min). After 8 hours, adsorbed platelets on PP was quantified via a lactate dehydrogenase assay. Compared to plain PP, the PMEA coating alone reduced adsorption by 17.4 +/- 9.2% and 29.6 +/- 16.6% at low and high flow (p < 0.05), respectively. NO was more effective at low plasma flow. At 100 and 500 ppm of NO, adsorption fell by 37.9 +/- 6.1% and 100 +/- 4.7%, (p < 0.001), on plain PP. At high flow with 100, 500, and 1000 ppm of NO, adsorption reduced by 17.9 +/- 17.8%, 46.4 +/- 23.2%, and 100 +/- 4.8%, (p < 0.001), respectively. On PMEA-coated PP with only 100 ppm, adsorption fell by 69.7 +/- 6.8 and 65.6% +/- 16.9%, (p < 0.001), at low and high flows respectively. Therefore, the combination of an anti-adsorptive coating with NO has great potential to reduce platelet adhesion and coagulation at biomaterial surfaces.