权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Magnetic Cellular Assembly and Microfluidic Conditioning for Generation of Functi

用于产生功能的磁性细胞组装和微流体调节

基本信息

批准号：
8574075
负责人：
Guruprasad A Giridharan
金额：
$ 47.64万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-13 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8574075
关键词：
Accounting Address Adult Affect American Architecture Behavior Biomechanics Biomedical Research Cardiac Cardiac Myocytes Cardiovascular Diseases Cardiovascular system Cell Culture Techniques Cell Density Cell Survival Cells Cessation of life Complex Cultured Cells Defect Dimensions Economic Burden Embryo Encapsulated Endothelial Cells Engineering Ensure Environment Exposure to Fibroblasts Gel Gene Expression Generations Goals Heart Hydrogels In Vitro Injury Lead Left ventricular structure Magnetism Mechanical Stress Mechanics Membrane Metabolic Microcirculation Microfluidics Modeling Morphology Myocardial Myocardial Infarction Myocardial tissue Natural regeneration Nutrient Pattern Perfusion Physiological Population Property Recreation Regenerative Medicine Regimen Role Seeds Site Stem cells Stretching Structure Techniques Technology Thick Tissue Engineering Tissue Grafts Tissues Work base cardiogenesis cell type cellular engineering clinically relevant conditioning conventional therapy density design experience flexibility in vivo magnetic field meetings monolayer nanoparticle pressure protein expression repaired scaffold stem tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular diseases affect 70 million Americans, resulting in an economic burden of $300 billion and accounting for nearly 40% of all deaths in the US. Conventional treatments of myocardial injury do not achieve myocardial regeneration. Therefore, stem cell and tissue engineering based approaches for cardiac tissue regeneration have been actively pursued. Existing scaffold based 3D tissue engineering approaches accomplish tissue regeneration in non-biomimetic environments and with limited control over 3D architecture. Mimicking the 3D cellular organization and replicating mechanical loading patterns seen in vivo will address shortcomings associated with conventional techniques and significantly enhance functionality of tissues generated in vitro. In this proposal, we will enable a platform technology for magnetic cellular assembly of multiple cell types encapsulated in magnetic hydrogels (M-Gels) that mimic the tissue-level cell densities to form 3D cardiac tissue structures. Microscale perfusion networks will be integrated into the 3D constructs to ensure delivery of nutrients and meet the high metabolic needs of cardiac cells. Patterned constructs will be cultured within a microfluidic Cardiac Cell Culture Model (CCCM) that accurately replicates pressure and stretch loading seen in the left ventricle. Our prior work clearly demonstrates our ability to pattern complex architectures in both 2D and 3D and accomplish cell culture within the CCCM under realistic mechanical stresses that promote cyclic stretch, cell alignment and spontaneous synchronous contractions. Specifically we will: (A) accomplish assembly of cardiac cells encapsulated in magnetic hydrogels (M-gels) around a sacrificial porogen network to attain in vivo like tissue-level cell densities and architecture, (B) utilize th CCCM to culture magnetically assembled cardiac tissue constructs in a cell culture environment that mimics the pressure-volume changes seen in the left ventricle and enable extraction of intact tissue following culture and (C) accomplish characterization of morphological and functional properties of magnetically assembled and microfluidically conditioned tissue constructs in vitro and determine the role of 3D patterning, integration of microscale perfusion networks and culture under loading regimens of pressure and stretch on in vitro cardiogenesis and the ability to generate functional myocardial tissue that can potentially be used to repair myocardial infarctions. Though chick embryonic cardiac cell populations will be used to demonstrate the feasibility of proposed activities, the developed techniques will be compatible with cardiac stem and progenitor cell populations for generation of functional cardiac patches.

心血管疾病影响7000万美国人，造成3000亿美元的经济负担，占美国所有死亡人数的近40%。心肌损伤的常规治疗不能实现心肌再生。因此，用于心脏组织再生的基于干细胞和组织工程的方法已经被积极地追求。现有的基于支架的3D组织工程方法在非仿生环境中实现组织再生，并且对3D架构的控制有限。模拟3D细胞组织和复制体内观察到的机械加载模式将解决与常规技术相关的缺点，并显着增强体外产生的组织的功能。在这项提案中，我们将实现一种平台技术，用于封装在磁性水凝胶（M-Gels）中的多种细胞类型的磁性细胞组装，模拟组织水平的细胞密度，以形成3D心脏组织结构。微尺度灌注网络将被集成到3D结构中，以确保营养物质的输送并满足心脏细胞的高代谢需求。将在微流体心脏细胞培养模型（CCCM）中培养图案化的构建体，该模型准确复制了左心室中观察到的压力和拉伸负荷。我们之前的工作清楚地表明了我们在2D和3D中图案化复杂架构的能力，并在CCCM内在现实的机械应力下完成细胞培养，促进循环拉伸，细胞排列和自发同步收缩。具体而言，我们将：（A）完成包封在磁性水凝胶（M-凝胶）中的心脏细胞在牺牲性致孔剂网络周围的组装，以获得体内类似组织水平的细胞密度和结构，（B）利用CCCM在细胞培养环境中培养磁性组装的心脏组织构建体，所述细胞培养环境模拟在左心室中观察到的压力-容积变化并且能够在培养后提取完整组织，以及（C）完成体外磁性组装和微流体调节组织构建体的形态和功能特性的表征，并确定3D图案化的作用，在压力和拉伸的负荷方案下整合微型灌注网络和培养物对体外心脏发生和产生可潜在用于修复心肌的功能性心肌组织的能力的影响梗塞虽然鸡胚心脏细胞群将用于证明拟议活动的可行性，但开发的技术将与心脏干细胞和祖细胞群兼容，用于生成功能性心脏补片。