Interactions at material-tissue interfaces are critical to the success of biomedical devices ranging from small devices like insulin cannulas and catheters, to complex artificial organs which are used in thousands of patients each day. Some of the common clinical problems that medical devices face today include infection, inflammation, foreign body response, and thrombosis. Hospital-acquired infections and rising rates of antibiotic-resistant bacterial strains that are becoming more common in the hospital setting remain serious concerns that affect millions of patients each year in the United States alone. These bacterial infections can lead to microbial biofilms that can cause various diseases and medical device infections that are notorious for being highly resistant to antibiotics. One promising approach to these biomedical device challenges is to develop therapeutic materials that deliver bioactive molecules, such as nitric oxide (NO), and mimic the mechanisms that the body uses to modulate inflammation, prevent blood clotting, and kill microbial infections. Nitric oxide is an endogenous gas molecule produced by nitric oxide synthase (NOS) enzymes that has several key biological roles. Healthy endothelial cells exhibit a NO surface flux of 0.5 – 4.0 x10-10 mol cm-2 min-1 that inhibits platelet adhesion and activation. Macrophages also release NO that acts as a potent broad-spectrum antimicrobial agent. This presentation will discuss work in synthesizing and developing NO-releasing polymers via incorporation of NO donor molecules which are characterized and optimized for their NO release, mechanical and surface properties, and stability properties. These materials are used to fabricate prototype devices (catheters, extracorporeal life support, insulin cannulas) and evaluated in clinically relevant animal models. The development of multifunctional small molecule therapeutics and biomaterial interfaces will also be discussed, which are a critical next step to promoting biocompatibility and overcoming these translational clinical challenges.

Engineering nitric oxide releasing polymeric biointerfaces to improve healthcare

ACS Spring 2022

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