Tissue Engineering Resource Center

组织工程资源中心

• 批准号: 10434732
• 负责人: Barry M. Fine
• 金额: $ 40.22万
• 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/10434732
• 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; Epithelial Cells; 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; base; 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 functioning; in vitro Model; induced pluripotent stem cell; injury recovery; 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.

概括 TRD3将专注于临床工程生物反应器的开发和实施 大小组织和整个器官，对生物过程进行定量实时成像，以及 确定天然整个器官病理状态疾病重塑的因素。 具体来说，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进行肺再生的生物反应器； (ii) 灌注 用于重现心肌梗塞后环境的生物反应器并研究其模式 心脏组织的再生。我们的假设是，这种新型成像生物反应器将 提供对组织再生所涉及的动态过程的深入见解，从而 促进对复杂组织和整个器官的有针对性的干预。两个具体目标将是 追击。目标 1 是开发一种用于功能再生的集成生物反应器成像系统 人类供体肺因不可接受移植而被拒绝并阐明相关因素 确定患病肺部纤维化过程的可逆性。生物反应器将允许 干预措施（例如去除和更换肺上皮，包括相关的外泌体） 肺部的目标区域（从上呼吸道一直到肺泡腔），持续 在干预和修复过程中对肺功能进行无创监测。目标 2 是开发一个 用于心脏组织再生的灌注生物反应器系统。该生物反应器的设计目的是 概括梗塞后环境并研究治疗方式，重点关注无细胞 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正的 根据测量的代谢参数控制培养基灌注的时间。总体而言，TRD3 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 为研究人员和临床医生提供平台，使他们能够获得对疾病的定量见解 组织和器官的生长和再生动力学，以促进肺的转化应用 缺血性心脏病的移植和治疗。