Autonomously Assembling Nanomaterial Scaffolds for Treating Myocardial Infarction

自主组装纳米材料支架治疗心肌梗塞

基本信息

批准号：
8548399
负责人：
Karen L Christman
金额：
$ 37.59万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-20 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8548399
关键词：
Acute Acute myocardial infarction Address American Angioplasty Animal Model Animals Architecture Area Award Biocompatible Materials Cardiac Catheters Cells Complication Country Data Detection Development Disadvantaged Early treatment Enzymes Extracellular Matrix Fluorescence Functional disorder Healed Heart Heart Transplantation Heart failure Home environment Hour In Situ In Vitro Infarction Infiltration Inflammatory Injection of therapeutic agent Innovative Therapy Knowledge Left Left Ventricular Remodeling Magnetic Resonance Imaging Matrix Metalloproteinases Modeling Myocardial Infarction Operative Surgical Procedures Patients Process Quality of life Rattus Recovery Recurrence Research Risk Rupture Staging Structure Syringes Testing Therapeutic Time Tissues Translations Ventricular Work base design experience healing high reward high risk improved in vivo innovation intravenous injection minimally invasive nanomaterials nanoparticle novel particle patient population pre-clinical prevent programs research clinical testing response scaffold statistics therapy design ventricular assist device

项目摘要

DESCRIPTION (provided by applicant): Each year approximately three quarters of a million Americans will have a new myocardial infarction (MI), and approximately half a million will have a recurrent MI. Approximately 37% of these patients will die from the MI within one year, and of those who do survive, two-thirds do not make a complete recovery, leading to an extremely large patient population that progresses to heart failure. No current therapies exist that directly address the negative left ventricular (LV) remodeling process that occurs post-MI and results in heart failure. These staggering statistics necessitate the development of new innovative therapies for MI. This research program will establish a new paradigm in the design of treatments for healing heart tissue post-MI. Specifically our plan is to develop self-assembling materials programmed to form a healing scaffold in damaged heart tissue immediately following MI. Currently, such early treatment is not possible because it would require direct injection of materials into inflamed tissue constituting an unacceptable risk. In the proposed, unprecedented approach, the materials are designed to be injected intravenously rather than directly into heart tissue. They will circulate, and assemble into the healing scaffold in response to inflammatory enzymes present in damaged heart tissue (matrix metalloproteinases, MMPs). We hypothesize that, if such a material could be delivered to a patient's heart within the first day post-MI, this could prevent significant damage by immediately stabilizing the extracellular matrix framework, and then promoting cell infiltration to alter the typical infarct process. The proposed research program will develop novel nanoparticles capable of forming a scaffold material architecture in response to MMPs in damaged heart tissue. This process of enzyme-directed assembly has been proven in vitro in preliminary studies. We aim to optimize and test these nanoparticles in established in vivo animal models. Our overarching aim is therefore to develop autonomously assembling nanomaterial scaffolds, which can be delivered via IV injection, target the area of acute MI, prevent and/or slow negative left ventricular remodeling, and improve cardiac function post-MI.

描述（由申请人提供）：每年大约有四分之三的美国人会患上新发的心肌梗塞 (MI)，大约有 50 万人会患有复发性心肌梗塞。这些患者中大约 37% 将在一年内死于心肌梗死，而在那些存活下来的患者中，三分之二没有完全康复，导致大量患者发展为心力衰竭。目前尚无直接治疗方法解决心肌梗死后发生的负性左心室 (LV) 重塑过程并导致心力衰竭。这些令人震惊的统计数据使得开发新的心肌梗死创新疗法成为必要。该研究项目将为心肌梗死后心脏组织的治疗设计建立新的范例。具体来说，我们的计划是开发自组装材料，编程为在心肌梗死后立即在受损的心脏组织中形成愈合支架。目前，这种早期治疗是不可能的，因为它需要将材料直接注射到发炎组织中，从而构成不可接受的风险。在所提出的前所未有的方法中，材料被设计为静脉注射，而不是直接注射到心脏组织中。它们将循环并组装成愈合支架，以响应受损心脏组织中存在的炎症酶（基质金属蛋白酶，MMP）。我们假设，如果这种材料可以在心肌梗死后的第一天内输送到患者的心脏，那么可以通过立即稳定细胞外基质框架来防止严重损伤，然后促进细胞浸润以改变典型的梗塞过程。拟议的研究计划将开发能够形成支架材料结构的新型纳米粒子，以响应受损心脏组织中的 MMP。这种酶引导的组装过程已在体外初步研究中得到证实。我们的目标是在已建立的体内动物模型中优化和测试这些纳米粒子。因此，我们的首要目标是开发自主组装的纳米材料支架，该支架可以通过静脉注射输送，靶向急性心肌梗死区域，预防和/或减缓负性左心室重构，并改善心肌梗死后的心脏功能。