Medical Device-Associated Infection and Thrombosis

Blood-material interaction is critical to the success of implantable medical devices. Devices range from simple catheters, stents, and grafts to complex extra-corporeal artificial organs. These biomedical devices are frequently used but have major limiting factors, including platelet adhesion lead to blood clotting. Despite decades of scientific understanding and engineering efforts around blood-surface interactions, the ideal non-thrombogenic prosthetic surface remains an unsolved problem. Another significant problem is that 1 out of every 20 central venous catheters results in at least one infection, with up to 40% of all indwelling catheter devices becoming infected. The CDC estimates that 1.7 million hospital-associated infections occur annually, leading up to 99,000 deaths per year at a cost of $28-45 billion.

The Macroscopic Problem of Device Failure Starts at the Microscopic Level

The hydrophobic surfaces of medical devices facilitate protein interactions, leading to coagulation cascade activation and clot formation.

Nitric Oxide to the Rescue

Nitric oxide (NO) is an endogenous free radical and gasotransmitter used throughout the body in the maintenance of vascular homeostasis, immune response, and neuronal stimulation. NO secreted by endothelial cells of the vascular lining maintains platelet quiescence, preventing platelets from sticking and avoiding clot formation. NO secreted at high doses by macrophages mediates immune response, in which NO can act as a progenitor of reactive oxygen and nitrogen species to mediate oxidative and nitrosative stress to microorganisms such as clinically relevant pathogens. Taking advantage of drug compounds that produce NO, our lab and others have developed NO-releasing materials to mimic physiological secretion of NO to mediate localized antithrombotic and antimicrobial effects on the surfaces of medical devices.

Nitric Oxide Release Prevents Thrombosis & Infection

Surface-localized release of NO is achieved through different drug delivery techniques, affording resistance to thrombosis and infection.

Combinatorial Strategies as An Emerging Paradigm

By pairing nitric oxide release with surface passivation strategies (e.g., hydrophilic topcoats, superhydrophobicity, liquid infusion, etc.), our lab has developed surface technologies for enhanced resistance to clot formation and bacterial infection, with efficacy demonstrated >30 d via both in vitro and in vivo preclinical testing. 

Active Drug Release and Surface Passivation Strategies for Enhanced Effect

Combination strategies enable a multi-pronged approach to prevention of protein-surface and cell interactions, preventing thrombosis and infection.

Our Mission

Our lab is committed to developing biocompatible coatings for medical devices through highly translational and interdisciplinary research. We perform fundamental cell/protein surface interaction studies, novel biomaterials development/optimization, and preclinical materials testing in animal models. Due to the critical nature of our research field, we have received NIH, CDC, and VA funding. Our novel materials stand to decrease the morbidity, mortality, and hospitalization costs associated with medical devices by reducing fouling, thrombosis and infection.

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