Reactive oxygen species scavenging with a biodegradable, thermally responsive hydrogel compatible with soft tissue injection

Tissue damage and the impairment of regenerative processes by excessive reactive oxygen species (ROS) contributes to the pathogenesis of various diseases in soft tissues including diabetes, atherosclerosis, Parkinson's disease and myocardial ischemic/reperfusion injury. In this study, a thermally responsive injectable hydrogel poly(NIPAAm-co-VP-co-MAPLA-co-MATEMPO) (pNVMT, NIPAAm: N-isopropylacrylamide, VP: vinylpyrrolidone, MAPLA: methacrylate-polylactide, MATEMPO: methacrylate-TEMPO, TEMPO: 4-amino-TEMPO or 4-Amino-2,2,6,6-tetramethylpiperidine-1-oxyl) incorporating recyclable ROS scavenging nitroxide radicals on the polymer backbone was developed to locally control adverse tissue effects from free radical generation. In an in vitro oxidative environment, TEMPO Gel significantly preserved cell viability. In a rat myocardial infarction/reperfusion model, TEMPO Gel diffused through the infarcted myocardium, integrated with the tissue upon gelation, and remained for over one week as visualized by MRI. The TEMPO Gel reduced infarction/reperfusion injury and preserved left ventricle geometry. This thermally responsive hydrogel was demonstrated to have properties desirable for local application to soft tissue beds where oxidative damage by ROS is of concern in pathological mechanisms.