NOS-Based Biopolymers: Towards Novel Thromboresistant No-Release Materials

Nitric Oxide releasing biopolymers have the potential to prolong vascular graft and stent potency without adverse systemic vasodilation. It was reported in literature that eNOS-overexpressing endothelial cell seeding of synthetic small diameter vascular grafts decreased human platelet aggregation by 46 and bovine aortic smooth muscle cell proliferation by 67.2 in vitro. We hypothesized that incorporating the enzyme nitric oxide synthase (NOS) in biocompatible polymeric matrix will provide a source of NO that utilizes endogenous compounds to maintain an unlimited supply of NO. To test this hypothesis, we have incorporated the enzyme nitric oxide synthase into a polyethyleneimine film using a layer-by-layer electrostatic deposition. This approach will provide a source of NO that utilizes endogenous compounds available in the blood matrix to maintain a constant supply of NO at the blood/device interface. When coated onto the surface of various blood-contacting implantable medical devices, it will provide NO fluxes at levels equal or greater than the normal endothelial cells, and for extended time periods. This configuration will help solve the issues of both thrombosis and stenosis that occur as side effects for several types of biomedical implants. Our results indicate a proof of principle of a new approach for making antithrombotic coatings for medical devices and implants based on NO release. We have demonstrated that NOS-based polymetric films successfully generate NO under physiologic conditions at small levels equal to and higher than those observed for endothelial cells. The level of NO release can be fine-tuned through varying the number of NOS layers in the film buildup. We have shown that NO fluxes from our NOS-based PEI films are sustained for prolonged periods of time, which has the potential of producing efficient, short and long-term, antithrombotic coatings for medical devices and blood-contacting tools such as stents and catheters. We also show that NO release from these coatings successfully dec