Engineering Vascularized Cardiac Muscle

工程血管化心肌

基本信息

批准号：
7900656
负责人：
Gordana Vunjak-Novakovic
金额：
$ 0.93万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2013-04-16
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7900656
关键词：
Acute myocardial infarction Adhesions Adult Area Bioreactors Blood Vessels Cardiac Cardiac Myocytes Cell Survival Cell Transplants Cells Cellular biology Cicatrix Coagulants Coculture Techniques Collaborations Congenital Abnormality Congestive Heart Failure Contracts Coupled Culture Media Data Elastomers Electric Stimulation Endothelial Cells Engineering Experimental Models Fibroblasts Generations Heart Diseases Histocompatibility Testing In Vitro Infarction Investigation Laboratories Left ventricular structure Modeling Molecular Muscle Cells Myocardial Myocardial Infarction Myocardial tissue Myocardium Natural regeneration Neonatal Nutrient Outcome Patients Perfusion Phenotype Physiological Rattus Research Resources Structure Testing Thick Tissue Engineering Tissues Universities Vascular Endothelial Cell Vascularization Wound Healing angiogenesis clinically relevant density design implantation in vivo injured migration molecular scale mortality muscle engineering repaired response scaffold vascular tissue engineering vasculogenesis

Acute myocardial infarction Adhesions Adult Area Bioreactors Blood Vessels Cardiac Cardiac Myocytes Cell Survival Cell Transplants Cells Cellular biology Cicatrix Coagulants Coculture Techniques Collaborations Congenital Abnormality Congestive Heart Failure Contracts Coupled Culture Media Data Elastomers Electric Stimulation Endothelial Cells Engineering Experimental Models Fibroblasts Generations Heart Diseases Histocompatibility Testing In Vitro Infarction Investigation Laboratories Left ventricular structure Modeling Molecular Muscle Cells Myocardial Myocardial Infarction Myocardial tissue Myocardium Natural regeneration Neonatal Nutrient Outcome Patients Perfusion Phenotype Physiological Rattus Research Resources Structure Testing Thick Tissue Engineering Tissues Universities Vascular Endothelial Cell Vascularization Wound Healing angiogenesis clinically relevant density design implantation in vivo injured migration molecular scale mortality muscle engineering repaired response scaffold vascular tissue engineering vasculogenesis

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项目摘要

DESCRIPTION (provided by applicant): Our current inability to vascularize and perfuse thick cell masses has hindered efforts to engineer many types of functional tissues including, most critically, cardiac muscle. To serve as a graft for myocardial repair, an engineered cardiac construct must be thick and compact, contain physiologic density of differentiated cells, and contract synchronously in response to electrical stimulation. In addition, the graft must have a capability to integrate with the host vasculature in order to maintain the viability and function of transplanted cells. We propose to engineer functional vascularized myocardium by integrating and advancing our ongoing efforts in the areas of cardiac tissue engineering (MIT) and vascular tissue engineering (Duke). We hypothesize that the cultivation of cardiac myocytes and endothelial cells on specialized scaffolds (highly porous, biodegradable, elastic, with an array of channels) in a bioreactor with medium perfusion and electrical stimulation will promote functional assembly of synchronously contractile engineered muscle. We further hypothesize that vascularization in vitro will enhance the graft capacity for survival, integration and function in vivo. In order to test these hypotheses, which have been derived from two lines of our previous investigations, we propose studies with the following Specific Aims: (1) High density culture of cardiac myocytes on channeled scaffolds with medium perfusion and electrical stimulation, (2) Tissue engineering of a vascularized network, and (3) Tissue engineering and functional characterization of a vascularized cardiac muscle. The effects of perfusion and electrical stimulation on the progression of endothelial cell and myocyte assembly into a synchronously contractile myocardium will be studied in vitro and in vivo (implantation onto a left ventricle in an adult rat model of infarction). Tissue structure and function will be characterized at various hierarchical scales (molecular, structural, functional) and the obtained experimental and modeling data will be used to tailor the conditions and duration of cultivation and engineer implantable grafts. As such, the current proposal is a blueprint for the generation of vascularized cardiac muscle suitable for implantation into injured myocardium.

描述（由申请人提供）：我们目前无法进行血管化和灌注厚的细胞肿块，阻碍了努力，以设计许多类型的功能组织，包括心脏肌肉。为了作为心肌修复的移植物，工程的心脏构建体必须厚而紧凑，包含分化细胞的生理密度，并响应于电刺激而同步收缩。此外，移植物必须具有与宿主脉管系统整合的能力，以维持移植细胞的生存能力和功能。我们建议通过整合和推进我们在心脏组织工程（MIT）和血管组织工程（DUKE）领域的持续努力来设计功能性血管化心肌。我们假设在具有中等灌注和电刺激的生物反应器中，在专门的脚手架（高度多孔，可生物降解，具有一系列通道的弹性）上培养心肌细胞和内皮细胞，将促进同步收缩工程的肌肉的功能组装。我们进一步假设体外血管化将增强体内生存，整合和功能的移植能力。为了测试这些假设，这些假设源自我们先前研究的两行，我们提出了以下特定目的的研究：（1）具有中等灌注和电刺激的通道支架上的心肌细胞的高密度培养，（2）血管性网络的组织工程，以及（3）组织工程和功能性的carsifatient Card Cards carcartic carcartic Card Cardcormity carcartic sasciact of Cast sasciact of Card sasciact of Card sasciact of Cars sous carcular sasciact of Cars sasciact of Cars sous carcultiac sasciact ass sasciact of Cast sasciact。将在体外和体内研究灌注和电刺激对内皮细胞和心肌组件进展为同步收缩的心肌的影响（植入成人梗死大鼠模型中的左心室）。组织结构和功能将在各种层次尺度（分子，结构，功能）下进行表征，并且获得的实验和建模数据将用于量身定制培养的条件和持续时间以及工程师的植入植物。因此，当前的建议是生成适合植入受伤心肌的血管肌肉的蓝图。