Biology the initiator: Harnessing Reactive Oxygen Species for Biocompatible Polymerization

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Project Title: Biology the initiator: Harnessing Reactive Oxygen Species for Biocompatible Polymerization Project Summary Vision: Disease or significant injury often results in rapid biochemical changes in the cellular environment. Reactive oxygen species (ROS) are significantly increased extracellularly following heart attack, burn injury or stroke, resulting in further cell death and tissue loss. What if these highly damaging radicals could be harnessed for good? This project will investigate the opportunity of biocompatible, ROS-initiated, polymerization to harness damaging extracellular radicals produced during significant disease or injury. ROS- initiated polymerization could potentially provide therapeutic benefits following injury resulting from an antioxidant effect, coupled with a synergistic benefit through the in-situ synthesis of a scaffold suitable for tissue regeneration. This approach of therapeutic polymerization could provide a paradigm shift in the way we treat diseases and injuries affected by oxidant damage where regeneration is required directly at the site of injury. This project will investigate the complexities of biocompatible polymerization for therapy and how biologically derived extracellular ROS can be used to directly initiate covalent polymerization. Advances in synthetic materials, that can alter function based on biological changes, are of great interest to generate materials which sense and adapt to different biological environments. These ‘smart’ materials have the potential to facilitate controlled drug release for disease and injury or modify the mechanical or chemical environment to alter cell signaling and improve regenerative capabilities. We hypothesize that ROS upregulation following disease or injury can be utilized to initiate polymerization for therapy and regeneration. This novel hypothesis will be tested by addressing three specific aims: (1) To synthesize biocompatible peptide-based monomers suitable for targeting ischemic tissue and undergoing ROS initiated polymerization, (2) to investigate the therapeutic benefit and regenerative support of extracellular ROS-initiated polymerizable scaffolds and (3) to demonstrate efficacy as a therapeutic strategy in a rat model of cardiac ischemia/reperfusion (I/R) injury. Success in this exploratory study bodes broad application where ROS is prevalent including heart disease, cancer, burn injuries and stroke among others.