A biomimetic reverse thermal gel for the treatment of myocardial infarction

一种治疗心肌梗塞的仿生反向热凝胶

基本信息

批准号：
8761159
负责人：
Dae Won Park
金额：
$ 21.49万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-22 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8761159
关键词：
Address Affect American Apoptosis Attention Behavior Binding Biocompatible Materials Biomimetics Biopolymers Blood Vessels Blood flow Body Temperature Bypass Cardiac Cardiovascular Diseases Cardiovascular system Catheters Cause of Death Cells Cessation of life Characteristics Charge Chemicals Communities Coronary Arteriosclerosis Coronary heart disease Development Diffusion Drug Formulations Echocardiography Educational process of instructing Endothelial Cells Ensure Environment Exhibits Extracellular Matrix Fibroblast Growth Factor 2 Gel Growth Factor Growth Factor Interaction Half-Life Heart Heparin Human In Situ In Vitro Infarction Injectable Injection of therapeutic agent Injury Inorganic Sulfates Ligands Liquid substance Location Medical Methods Modeling Molecular Conformation Monitor Morbidity - disease rate Myocardial Myocardial Infarction Myocardial Ischemia Myocardial tissue Natural regeneration Needles Nutrient Operative Surgical Procedures Oxygen Patients Pharmaceutical Preparations Polymers Property Rattus Recovery Recovery of Function Recurrence Research Project Grants Rodent Site Sol-Gel Phase Transitions Solid Solutions Structure System Temperature Therapeutic Time Tissue Engineering Tissues Tube Umbilical vein Unspecified or Sulfate Ion Sulfates Vascular Endothelial Growth Factors Vascular blood supply Vascularization Work alternative treatment angiogenesis base biomaterial compatibility cell behavior compliance behavior experience functional group global health heart function improved in vivo interest minimally invasive mortality novel percutaneous coronary intervention physical property public health relevance research and development response scaffold success treatment effect treatment strategy

项目摘要

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.

描述（由申请人提供）：估计每年有63.5万美国人患有冠状动脉疾病（CAD），显然需要采取替代治疗策略。心肌梗死（MI）是由心肌组织死亡引起的主要CAD。当前的治疗范式集中于药理学（减少氧气需求或增加血液流动）或手术干预措施，包括手术旁路以重建血液流动路径。最近的工作采用了一种更生物医学的方法，在这种方法中，使用梗塞部位中使用生长因子的血管生成作为提供血流和氧气供应的一种手段。尽管某些方法取决于直接给予纯生长因素，但心血管组织工程更广泛领域的经验告诉我们，基于脚手架的方法可能是最有前途的策略。我们最近开发了一种可注入的聚合物生物材料，该材料适用于这种应用，这是由于反向热胶凝特性。这些属性使其过于快速，可逆地过渡在室温下的液体和在体温下的固体之间，可以直接在目标部位通过小规格针或导管注射，然后在达到体温后形成粘性的固体聚合物网络。这种方法比其他基于脚手架的方法具有许多优势，包括微创部署，原位对伤害部位和可调物理特性，以模仿宿主环境。此外，该系统可以很容易地将天然肝素的特异性生物功能化，从而增强生长因子的稳定性和局部表达，从而在MI部位实现局部血管生成，并具有大量的心脏功能恢复。为了开发一种可以最大化这些优势的系统，我们围绕两个具体的目的构建了此应用：1）确定合适的模拟肝素反向热凝胶（SRTG）的适当版本，该版本在体外实质上维持生长因子的表达和2）证明了实质性的血管生成和实质性的血管生成和体内大鼠MI模型的MI治疗效果。