Glycocalyx-Inspired Nitric Oxide-Releasing Surfaces Reduce Platelet Adhesion and Activation on Titanium

Abstract

The endothelial glycocalyx lining the inside surfaces of blood vessels has multiple features that prevent inflammation, blood clot formation, and infection. This surface represents the highest standard in blood compatibility for long-term contact with blood under physiological flow rates. Engineering materials used in blood-contacting biomedical devices, including metals and polymers, have undesirable interactions with blood that lead to failure modes associated with inflammation, blood clotting, and infection. Platelet adhesion and activation are key events governing these undesirable interactions. In this work, we propose a new surface modification to titanium with three features inspired by the endothelial glcyocalyx: First, titanium surfaces are anodized to produce titania nanotubes with high surface area. Second, the nanostructured surfaces are coated with heparin-chitosan polyelectrolyte multilayers to provide glycosaminoglycan functionalization. Third, chitosan is modified with a nitric oxide-donor chemistry to provide an important antithrombotic small-molecule signal. We show that these surfaces are nontoxic with respect to platelets and leukocytes. The combination of glycocalyx-inspired features results in a dramatic reduction of platelet and leukocyte adhesion and platelet activation.

Keywords: blood compatibility; cardiovascular materials; heparin; platelet activation; surface modification; titanium.