The goal of this award is to develop an expert in blood/materials science. Why this project;why this candidate;and why this environment? Blood flows through the envelope of endothelium for a lifetime without clotting. When blood contacts anything but endothelium (collagen tissue, air, metal, plastic) it clots in a few seconds. This is normal physiology. Most of modern medicine depends on understanding these phenomena. We take advantage of it to allow all surgical procedures from venipuncture to transplantation. We try to prevent it when blood contacts medical devices from simple catheters to complex artificial organs. Better understanding of the physiology will result in better, safer blood contact devices which will impact all of medicine. For 100 years this research was focused on the components of the blood. Now it is focused on the endothelium. A blood/materials expert brings basic engineering and biologic science to the benefit of patients in every field of medicine. Dr. Hitesh Handa has the basic engineering knowledge. He also has the practical experience in development of blood contact devices. To this background he will add the chemistry of the endothelium, the biologic systems to evaluate materials, and experience in clinical application. In five years he will be on the small but vital roster of experts in blood/materials science. The combination of mentors, facilities and expertise at the University of Michigan provides an outstanding environment for Dr. Handa's development. Dr. Bartlett is a clinical surgeon and intensivist who has taken clinical problems to the biology laboratory for decades. Dr. Mark Meyerhoff is a basic scientist who has taken molecular chemistry to the biology laboratory for decades. Their combined research is focused on simulating the normal endothelium. Their students are among the experts in blood/materials science, from chemists and research biologists to industrial developers to clinical practitioners. .
Blood/material interaction is central to devices in medical care. Devices from simple catheters to implantable vessels and stents to complex extracorporeal artificial organs are used in millions of patients every day. This project will focus on training Dr. Handa to become an independent investigator in biocompatible materials. The research proposed in this application addresses the development and application of NO secreting materials, alone and in combination with other surface modifications, for short and long-term applications.
|Brisbois, Elizabeth J; Bayliss, Jill; Wu, Jianfeng et al. (2014) Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model. Acta Biomater 10:4136-42|
|Suchyta, Dakota J; Handa, Hitesh; Meyerhoff, Mark E (2014) A nitric oxide-releasing heparin conjugate for delivery of a combined antiplatelet/anticoagulant agent. Mol Pharm 11:645-50|
|Handa, Hitesh; Major, Terry C; Brisbois, Elizabeth J et al. (2014) Hemocompatibility Comparison of Biomedical Grade Polymers Using Rabbit Thrombogenicity Model for Preparing Nonthrombogenic Nitric Oxide Releasing Surfaces. J Mater Chem B Mater Biol Med 2:1059-1067|
|Major, Terry C; Brisbois, Elizabeth J; Jones, Anna M et al. (2014) The effect of a polyurethane coating incorporating both a thrombin inhibitor and nitric oxide on hemocompatibility in extracorporeal circulation. Biomaterials 35:7271-85|
|Major, Terry C; Handa, Hitesh; Brisbois, Elizabeth J et al. (2013) The mediation of platelet quiescence by NO-releasing polymers via cGMP-induced serine 239 phosphorylation of vasodilator-stimulated phosphoprotein. Biomaterials 34:8086-96|
|Brisbois, Elizabeth J; Handa, Hitesh; Major, Terry C et al. (2013) Long-term nitric oxide release and elevated temperature stability with S-nitroso-N-acetylpenicillamine (SNAP)-doped Elast-eon E2As polymer. Biomaterials 34:6957-66|