Tissue Engineering Resource Center

组织工程资源中心

• 批准号: 10683747
• 负责人: Barry M. Fine
• 金额: $ 39.01万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10683747
• 关键词: Air; Alveolar; Biological Process; Biomimetics; Bioreactors; Blood Substitutes; Cardiac; Cardiac Myocytes; Cardiopulmonary; Cell Therapy; Cell Transplantation; Cells; Cellular Metabolic Process; Clinic; Clinical; Clinical Engineering; Complex; Coupled; Culture Media; Development; Devices; Disease; Distal; Encapsulated; Environment; Epithelial Cells; Epithelium; Evaluation; Excision; Functional Regeneration; Functional disorder; Goals; Growth; Heart; Heart Injuries; Human; Hydrogels; Image; In Situ; Infarction; Intervention; Ischemia; Liver; Lung; Lung Transplantation; Lung diseases; Maintenance; Measures; Medicine; Metabolic; Mission; Modality; Modeling; Monitor; Myocardial; Myocardial Infarction; Myocardial Ischemia; Natural regeneration; Organ; Output; Pathologic; Perfusion; Phenotype; Physiological; Procedures; Process; Recovery; Regenerative engineering; Research Personnel; Resources; Series; Stomach; Structure of parenchyma of lung; Supporting Cell; System; Technology; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Uses; Time; Tissue Engineering; Tissue constructs; Tissues; Translations; Transplantation; Visual; aspirate; blood perfusion; cardiac regeneration; cardiac tissue engineering; cardiopulmonary system; cell type; cytokine; design; exosome; human tissue; image guided; imaging modality; imaging platform; imaging system; improved; in vitro Model; induced pluripotent stem cell; innovation; insight; lung basal segment; lung injury; lung regeneration; lung repair; minimally invasive; next generation; non-invasive monitor; novel; operation; organ regeneration; public health relevance; pulmonary function; quantitative imaging; real-time images; regenerative; repaired; response; technology development; tissue regeneration; tissue repair; translational applications; ventilation

SUMMARY TRD3 will focus on the development and implementation of bioreactors for engineering clinically sized tissues and whole organs, with quantitative real-time imaging of biological processes, and determination of factors of disease remodeling of pathologic states in native whole organs. Specifically, we plan to develop two classes of next-generation bioreactor systems: (i) Visually guided bioreactors for lung regeneration by targeted cell replacement and bioactive agents; and (ii) Perfusion bioreactor for recapitulation of the post-myocardial infarct environment and study the modalities for regeneration of heart tissue. Our hypothesis is that this new class of imaging enabled bioreactors will provide considerable insights into the dynamic processes involved in tissue regeneration and thereby facilitate targeted interventions in complex tissues and whole organs. Two specific aims will be pursued. Aim 1 is to develop an integrated bioreactor-imaging system for functional regeneration of human donor lungs rejected as unacceptable for transplantation and to elucidate the factors associated with the determination of reversibility of the fibrotic process in diseased lungs. The bioreactor will allow interventions (such as removal and replacement of lung epithelium including associated exosomes) in targeted regions of the lung (from the upper airway all the way to alveolar spaces), with continuous non-invasive monitoring of the lung function during interventions and repair. Aim 2 is to develop a perfusion bioreactor system for heart tissue regeneration. The bioreactor will be designed to recapitulate the post infarct environment and investigate therapeutic modalities, with focus on cell-free treatment using exosomes secreted by therapeutic cells. An integrated controller will allow for the real time control of medium perfusion in response to measured metabolic parameters. Overall, the TRD3 projects aim to advance the field of tissue engineering by offering these unique bioreactor-imaging platforms to investigators as well as clinicians, and enabling them to obtain quantitative insights into the dynamics of growth and regeneration of tissues and organs to promote translational applications in lung transplantation and management of ischemic heart disease.

总结 TRD 3将专注于临床工程生物反应器的开发和实施 大小的组织和整个器官，具有生物过程的定量实时成像，以及 确定天然整个器官病理状态的疾病重塑因素。 具体而言，我们计划开发两类下一代生物反应器系统：（i）视觉引导 通过靶向细胞替代和生物活性剂用于肺再生的生物反应器;和（ii）灌注 生物反应器的心肌梗死后的环境重演，并研究的方式， 心脏组织的再生我们的假设是，这种新型的成像生物反应器将 为组织再生中涉及的动态过程提供了相当多的见解， 有助于对复杂组织和整个器官进行有针对性的干预。两个具体目标将是 追求。目的1是开发一个集成的生物反应器成像系统，用于功能性再生。 人类供体肺因移植不可接受而被拒绝，并阐明相关因素 确定病变肺中纤维化过程的可逆性。生物反应器将允许 干预（如去除和替换肺上皮，包括相关的外来体）， 肺的目标区域（从上气道一直到肺泡空间）， 在介入和修复过程中对肺功能进行无创监测。目标二是发展一个 用于心脏组织再生的灌注生物反应器系统。生物反应器将被设计为 概括梗死后环境并研究治疗方式，重点是无细胞 使用治疗细胞分泌的外泌体进行治疗。集成控制器将允许真实的 响应于测量的代谢参数的培养基灌注的时间控制。总的来说，TRD 3 项目旨在通过提供这些独特的生物反应器成像来推进组织工程领域 为研究者和临床医生提供平台，使他们能够获得对 组织和器官的生长和再生动力学以促进肺中的转化应用 移植和缺血性心脏病的管理。