Biology the initiator: Harnessing Reactive Oxygen Species for Biocompatible Polymerization

项目名称： 生物引发剂：利用活性氧进行生物相容聚合 项目摘要 视力：疾病或重大损伤通常会导致细胞环境的快速生化变化。 在心脏病发作、烧伤或死亡后，细胞外活性氧类(ROS)显著增加。 中风，导致进一步的细胞死亡和组织丢失。如果这些极具破坏性的激进分子 永远被利用了？该项目将调查生物兼容、ROS发起、 聚合作用，以利用在重大疾病或损伤期间产生的破坏性细胞外自由基。ROS- 引发聚合可能在抗氧化剂造成的损伤后提供治疗益处 效果，再加上通过原位合成适合组织的支架的协同效益 再生。这种治疗性聚合的方法可以提供我们治疗方式的范式转变 受氧化剂损伤影响的疾病和损伤，在损伤部位需要直接再生。 该项目将研究用于治疗的生物相容性聚合的复杂性以及如何 生物来源的胞外ROS可用于直接引发共价聚合。 可以根据生物变化改变功能的合成材料的进展对 产生能够感知和适应不同生物环境的材料。这些“智能”材料具有 促进疾病和损伤的受控药物释放或改变机械或化学物质的可能性 改变细胞信号和提高再生能力的环境。我们假设ROS 疾病或损伤后的上调可用于启动聚合治疗和 再生。这一新的假设将通过解决三个具体目标来检验：(1)合成 适用于靶向缺血组织和启动ROS的生物相容多肽单体 聚合，(2)研究胞外ROS启动的治疗效果和再生支持 可聚合支架和(3)作为一种治疗策略在大鼠心脏模型中的有效性 缺血再灌注(I/R)损伤。这项探索性研究的成功预示着ROS在哪里有广泛的应用 常见的疾病包括心脏病、癌症、烧伤和中风等。

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.