Biology the initiator: Harnessing Reactive Oxygen Species for Biocompatible Polymerization

生物学引发者：利用活性氧进行生物相容性聚合

• 批准号: 10667740
• 负责人: Tristan Clemons
• 金额: $ 18.5万
• 依托单位: UNIVERSITY OF SOUTHERN MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667740
• 关键词: Acrylamides; Address; Affect; Antioxidants; Binding Sites; Biochemical; Biocompatible Materials; Biological; Biological Assay; Biology; Burn injury; Cell Death; Cell Survival; Cell surface; Chemicals; Chemistry; Collaborations; Consumption; Coupled; Disease; Environment; Extracellular Matrix; Heart Diseases; In Situ; In Vitro; Injury; Intervention; Ischemia; Label; Literature; Malignant Neoplasms; Mammalian Cell; Mechanics; Medical center; Mississippi; Modeling; Modification; Morbidity - disease rate; Myocardial Infarction; Myocardial Ischemia; Natural regeneration; Oxidants; Oxidative Stress; Peptide Synthesis; Peptides; Pharmaceutical Preparations; Physiological; Play; Polymers; Production; Public Health; Rattus; Reaction; Reactive Oxygen Species; Recovery; Reperfusion Injury; Role; Signal Transduction; Site; Stroke; Structure; Techniques; Testing; Therapeutic; Therapeutic Effect; Tissues; Universities; Up-Regulation; Vision; Vitamin K 3; Work; antioxidant therapy; bioactive scaffold; biocompatible polymer; biomaterial compatibility; biomaterial development; cell injury; crosslink; efficacy evaluation; extracellular; improved; in vitro Model; in vivo Model; innovation; interest; ischemic injury; monomer; mortality; novel; novel therapeutics; peptide amphiphiles; physiologic stressor; polymerization; regeneration potential; regenerative; scaffold; success; technology platform; therapy development; tissue regeneration; tissue support frame

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.

项目名称： 生物学引发剂：利用活性氧进行生物相容性聚合 项目摘要 疾病或严重损伤通常会导致细胞环境的快速生化变化。 在心脏病发作、烧伤或其他损伤后，细胞外活性氧（ROS）显著增加。 中风，导致进一步的细胞死亡和组织损失。如果这些极具破坏力的自由基 永远被驾驭了吗本项目将研究生物相容性，ROS启动， 聚合以利用在显著疾病或损伤期间产生的破坏性细胞外自由基。ROS- 引发的聚合可能在抗氧化剂引起的损伤后提供治疗益处 通过原位合成适用于组织的支架， 再生这种治疗聚合的方法可以为我们治疗 受氧化损伤影响的疾病和损伤，其中损伤部位需要直接再生。 该项目将调查生物相容性聚合治疗的复杂性，以及如何 生物衍生的细胞外ROS可用于直接引发共价聚合。 合成材料的进展，可以改变基于生物变化的功能，是非常感兴趣的， 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 促进疾病和损伤的药物控释或改变机械或化学性质的潜力 环境，以改变细胞信号传导和提高再生能力。我们假设ROS 疾病或损伤后的上调可用于引发治疗用聚合， 再生这一新的假设将通过解决三个具体目标进行测试：（1）合成 适用于靶向缺血组织并经历ROS引发的生物相容性肽基单体 聚合，（2）研究细胞外ROS引发的治疗益处和再生支持， 可聚合支架和（3）在心脏病大鼠模型中证明作为治疗策略的功效 缺血/再灌注（I/R）损伤。这项探索性研究的成功预示着ROS的广泛应用， 这些疾病包括心脏病、癌症、烧伤和中风等。