A biomimetic reverse thermal gel for the treatment of myocardial infarction

描述（由申请人提供）：估计每年有635,000名美国人患有冠状动脉疾病（CAD），显然需要一种替代治疗策略。心肌梗死（MI）是由心肌组织死亡引起的主要冠心病。目前的治疗模式主要集中在药物治疗（减少需氧量或增加血流量）或手术干预，包括手术搭桥重建血流路径。最近的研究采用了一种更加生物医学的方法，即在梗死部位使用生长因子进行血管生成，作为提供血液流动和氧气供应的手段。虽然一些方法依赖于纯生长因子的直接管理，但在心血管组织工程更广泛领域的经验告诉我们，基于支架的方法可能是最有前途的策略。我们最近开发了一种聚合物注射生物材料，由于其反向热胶凝特性，它很好地服务于这种应用。这些特性使得它的转变过于迅速和可逆

DESCRIPTION (provided by applicant): With an estimated 635,000 Americans with coronary artery disease (CAD) each year, there is a clear need for an alternative treatment strategy. Myocardial infarction (MI) is a leading CAD caused by the death of heart muscle tissues. The current treatment paradigm is focused on pharmacological (reducing oxygen demand or increasing blood flow) or surgical intervention including surgical bypass to reconstruct blood flow path. Recent work has taken a more biomedical approach in which angiogenesis using growth factors in infarction site is targeted as a means to provide blood flow and oxygen supply. While some approaches are dependent on direct administration of pure growth factors, experience in the wider field of cardiovascular tissue engineering has taught us that a scaffold-based approach may be the most promising strategy. We have recently developed a polymeric injectable biomaterial that serves itself well to this application owing to is reverse thermal gelling properties. These properties allow it too rapidly and reversibly transition between a liquid at room temperature and a solid at body temperature, permitting injection through a small gauge needle or catheter directly at the target site and then formation of a cohesive solid polymer network upon reaching body temperature. This approach has many advantages over other scaffold-based approaches including minimally- invasive deployment, in situ conformation to the injury site and tunable physical properties to mimic the host environment. In addition, this system can be readily functionalized to mimic specific biofunction of natural heparin to enhance stability and localized expression of growth factors, and thereby achieve localized angiogenesis in MI site with substantial recovery of heart function. Towards developing a system that can maximize these advantages, we have constructed this application around two specific aims: 1) determine appropriate version of heparin-mimicking reverse thermal gel (SRTG) that substantially sustains growth factor expression in vitro and 2) demonstrate substantial angiogenesis and MI treatment effect by in vivo rat MI model.