DEPSCOR: Development of a Targeted Antioxident Polymers for the Prevention of Combat Trauma Related Iachemia/Reperfusion--Chip & Polymer Design Sections

The goal of this project is to develop a targeted antioxidant particle system as a means of inhibiting ischemia/reperfusion (I/R) related injury. The specific aims of this project include the: 1.) synthesis and characterization of a new antioxidant polymer capable of long term storage and tunable control over antioxidant release, 2.) development of a new microfluidic cell culture model for evaluating in real time I/R induced endothelial cell activation, and 3.) synthesis of endothelial cell targeted nanoparticles and analysis of their therapeutic function in the in vitro I/R model developed in aim 2. Ischemia reperfusion is a common pathological process that is seen in a variety of combat trauma settings, including tourniquet related I/R and reduced perfusion due to hemorrhagic shock. By providing a targeted, controlled release vehicle for the delivery of antioxidants, it is expected that the oxidative stress injury that occurs as a result of I/R can be greatly attenuated. This attenuation is expected to greatly improve outcomes by preventing organ injury and muscle tissue edema. Specifically, we will be studying the effects of biodegradable polymer composed of the antioxidant, Trolox (a water soluble Vitamin E analog) to controllably release antioxidants and suppress I/R injury. It is expected that the methods developed in this study can be applied to a wide range of antioxidants and other therapeutics as a means of enhancing the robustness of the developed therapy. Cell culture methods for evaluating I/R injury are cumbersome and often difficult to implement. In an effort to provide a means of enhancing the basic science of EC I/R studies and provide a easy to use test best for studying antioxidant nanoparticles, we will also develop a lowtemperature cofired ceramic (LTCC) microfluidic chip system for monitoring EC status in real time. It is expected that the development of this basic cell culture tool will aide in the study of multiple fundamental I/R endothelial cell response and signaling questions. Finally, the development of these two areas through the awarding of this grant will aide in the long term goal of establishing a University of Kentucky center on Bioactive interfaces and devices by 1.) providing a proof of principle capability of new technologies currently being developed on campus and 2.) aiding in the establishment of new and important collaborations between the University of Kentucky and Department of Defense (000) entities.