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.
