Tissue Engineering Resource Center

组织工程资源中心

• 批准号: 10021421
• 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
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10021421
• 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; Engineering; Environment; Epithelial; Epithelial Cells; Epithelium; Evaluation; Excision; 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; Research Personnel; Resources; Respiratory physiology; Series; Stomach; Structure of parenchyma of lung; Supporting Cell; System; Technology; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Uses; Time; Tissue Engineering; 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; quantitative imaging; real-time images; regenerative; repaired; response; technology development; tissue regeneration; tissue repair; 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.

摘要 TRD3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，具有生物过程的实时定量成像，以及 天然整体脏器病理状态的疾病重塑因素测定。 具体地说，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物质用于肺再生的生物反应器；及(Ii)灌流 用于重现心肌梗死后环境的生物反应器和研究治疗方法 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 提供对组织再生所涉及的动态过程的相当深入的见解 促进对复杂组织和整个器官的定向干预。两个具体目标将是 被追捕。目标1是开发一种集成的生物反应器-成像系统，用于功能再生 拒绝接受人类供体肺移植并阐明相关因素 以确定病变肺纤维化过程的可逆性。生物反应器将允许 干预措施(如切除和替换肺上皮，包括相关的外切体) 肺的目标区域(从上呼吸道一直到肺泡腔)，连续 介入和修复过程中肺功能的非侵入性监测。目标2是开发一种 心脏组织再生的灌流生物反应器系统。生物反应器将被设计成 总结梗死后的环境和研究治疗方式，重点是无细胞 使用治疗细胞分泌的外切体进行治疗。集成的控制器将允许真正的 根据测量的代谢参数控制介质灌流的时间。总体而言，TRD3 这些项目旨在通过提供这些独特的生物反应器成像来推动组织工程领域的发展 平台提供给研究人员和临床医生，使他们能够获得对 促进肺内翻译应用的组织和器官的生长和再生动力学 缺血性心脏病的移植和治疗。