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.

Medical device-associated bacterial infections remain a significant complication for patients on extracorporeal organ support. Device-specific bacterial infections occur when bacteria enter the host tissue and attach to the devices, enabling bacteria to colonize and multiply rapidly. Preventing bacterial attachment would efficiently inhibit colonization and biofilm formation. In this study, a copper-based metal−organic framework (MOF) with demonstrated stability under physiological conditions was dispersed in a polymer solution and applied to the interior surface of seven-foot-long medical circulation tubing via a custom-designed coating system. The resulting MOF coating was thin and uniform along the entire length of the tubing. The coating was stable after dynamic flow without degradation or changes to the surface morphology. Bacterial attachment studies were performed on MOF-embedded medical tubing and uncoated control tubing under static and dynamic flow conditions for 24 h. Staphylococcus aureus (S. aureus) attachment was reduced by 52 ± 15% (static conditions) and 53 ± 29% (dynamic conditions) on the MOFcoated tubing compared to uncoated controls. In addition, S. aureus attachment was reduced by 52 ± 12% (MOF coating) and 52 ± 30% (uncoated controls) under dynamic flow conditions compared to static conditions. This study is the first to show the promising antibacterial performance of a MOF coating on medical tubing under both static and dynamic flow conditions.

Thrombosis is one of the most critical challenges faced by successful clinical use of blood-contacting medical devices. The formation of blood clots on medical device surfaces is a multistep process that includes protein adsorption, platelet adhesion and activation, and platelet aggregation, resulting in platelet consumption and blockage of blood flow. Without proper treatment, thrombosis will lead to ultimate device failure and create complications in patients. Nitric oxide (NO), a small signaling molecule generated from natural endothelial cells, has been widely shown to reduce platelet adhesion and activation, which occurs in the second step of blood clotting cascade. However, few studies have investigated the effect of NO on protein adsorption, which is the first step of blood clotting cascade. In this study, the effects of NO on fibrinogen (Fb) adsorption and subsequent effects of Fb on platelet adhesion and activation were investigated. This was done by using a model NO-releasing polymer film system, plasticized poly(vinyl chloride) (PVC) and -nitrosoglutathione, to examine how NO-mediated pre-adsorbed Fb, a major blood serum protein that initiates the blood clotting cascade, affects platelet adhesion and activation. The NO-releasing polymer films were found to increase Fb adsorption, but decrease platelet adhesion and activation on the surface when compared to plasticized PVC control films. Further, to eliminate the effects of NO on platelets, NO-releasing polymer films were first exposed to Fb and then incubated until all NO was released. This experiment isolates the effect of NO-mediated pre-adsorbed Fb on platelets in the absence of continuing NO release. Surprisingly, the results show that films with adsorbed Fb that no longer release NO continue to prevent platelet adhesion and activation. This study suggests that NO can affect adsorbed Fb to further prevent platelet adhesion and activation.

Introduction: Clot formation, infection, and biofouling are unfortunate but frequent complications associated with the use of blood-contacting medical devices. The challenge of blood-foreign surface interactions is exacerbated during medical device applications involving substantial blood contact area and extended duration of use, such as extracorporeal life support (ECLS). We investigated a novel surface modification, a liquid-impregnated surface (LIS), designed to minimize protein adsorption and thrombus development on medical plastics. Methods: The hemocompatibility and efficacy of LIS was investigated first in a low-shear model with LIS applied to the lumen of blood incubation vials and exposed to human whole blood. Additionally, LIS was evaluated in a 6 h ex vivo circulation model with swine blood using full-scale ECLS circuit tubing and centrifugal pumps with clinically relevant flow rate (1.5 L/min) and shear conditions for extracorporeal carbon dioxide removal. Results: Under low-shear, LIS preserved fibrinogen concentration in blood relative to control polymers (+40 ± 6 mg/dL vs polyvinyl chloride, p < .0001), suggesting protein adsorption was minimized. A fibrinogen adhesion assay demonstrated a dramatic reduction in protein adsorption under low shear (87% decrease vs polyvinyl chloride, p = .01). Thrombus deposition and platelet adhesion visualized by scanning electron microscopy were drastically reduced. During the 6 h ex vivo circulation, platelets in blood exposed to LIS tubing did not become significantly activated or procoagulant, as occurred with control tubing; and again, thrombus deposition was visually reduced. Conclusions: A LIS coating demonstrated potential to reduce thrombus formation on medical devices. Further testing is needed specialized to clinical setting and duration of use for specific medical target applications.