Tissue Engineering Resource Center

组织工程资源中心

• 批准号: 10213715
• 负责人: Gordana Vunjak-Novakovic
• 金额: $ 40.17万
• 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/10213715
• 关键词: 3-Dimensional; Address; Arrhythmia; Automation; Back; Behavior; Biocompatible Materials; Biological; Bioluminescence; Bioreactors; Bone Tissue; Cardiac; Cell Line; Cell Survival; Cell membrane; Cells; Cessation of life; Controlled Study; Development; Devices; Differentiation Antigens; Disease model; Dose; Electric Stimulation; Engineering; Feedback; Genes; Genetic Engineering; Genetic Transcription; Goals; Health; Image; In Vitro; Light; Lighting; Luminescent Proteins; Mechanical Stimulation; Membrane; Membrane Potentials; Metastatic breast cancer; Mission; Modeling; Molecular; Monitor; Optics; Oxygen; Pathologic; Patients; Pattern; Physiological; Production; Proteins; Rapid screening; Real-Time Systems; Regenerative Medicine; Reproducibility; Resolution; Resources; System; Technology; Testing; Thick; Time; Tissue Engineering; Tissues; Toxic effect; Transgenic Organisms; Work; base; biological systems; biomaterial compatibility; bone; cancer cell; cell type; design; flexibility; genetically modified cells; human disease; human model; imaging modality; imaging platform; imaging system; implantable device; implantation; in vivo; migration; molecular marker; neuromuscular; novel; novel strategies; optogenetics; preservation; promoter; quantitative imaging; response; shear stress; spatiotemporal; tissue culture; tumor; voltage

Summary TRD2 will focus on the development of cell lines and advanced optical systems for real-time spatiotemporal control of engineered tissues. Cell lines will be genetically engineered to express bioluminescent proteins for quantitative and real-time sensing, and optogenetic proteins for optical actuation. The hypothesis is that the integration of transgenic tissues expressing these proteins with advanced optical systems will enable real-time feedback control of engineered tissues in a spatiotemporal manner. In conjunction with traditional bioreactors, these systems will allow for the automation and optimization of tissue culture systems capable of rapidly screening many parameters in a variety of contexts. Three specific aims will be pursued. Aim 1: Imaging-enabled bioreactors for disease modeling. A tissue-engineered model of metastatic breast cancer in bone will be used to optimize the chemotherapeutic dose using a feed back control loop for the maximization of efficacy and minimization of toxicity. Aim 2: Optogenetic bioreactors for electrically excitable tissues with feedback control. Using this strategy we will enable directed stimulation and maturation of engineered cardiac and neuromuscular tissues and study the control of cardiac arrhythmias. Aim 3: Bioreactors and implantable devices for excitation/sensing in thick tissues. These capabilities will be used to develop light conduits for excitation/sensing in living tissues and implantable devices for optical actuation. Overall, TRD2 will result in a suite of optical systems, optically active cell lines, and advanced bioreactors for enhanced sensing, actuation, and control in tissue engineered systems. Our initial focus will be on bioluminescence and optogenetics, with the ultimate goal to develop optically compatible cells, biomaterials and devices to interface with engineered tissues, in vitro and in vivo.

概括 TRD2将专注于实时的细胞系和高级光学系统的开发 工程组织的时空控制。细胞系将经过基因设计以表达 用于定量和实时传感的生物发光蛋白，以及光学遗传蛋白的光学蛋白 致动。假设是表达这些蛋白质的转基因组织的整合 先进的光学系统将实现时空中工程组织的实时反馈控制 方式。与传统的生物反应器一起，这些系统将允许自动化和 优化的组织培养系统能够快速筛选多种参数 上下文。将追求三个具体目标。 AIM 1：支持疾病的成像生物反应器 造型。骨骼中转移性乳腺癌的组织工程模型将用于优化 化学治疗剂量使用饲料后控制回路，以最大程度地提高功效和最小化 毒性。 AIM 2：具有反馈控制的电激发组织的光遗传生物反应器。使用 我们将实现该策略的定向刺激和工程心脏和神经肌肉的成熟 组织并研究心律不齐的控制。目标3：生物反应器和可植入设备 厚组织中的激发/传感。这些功能将用于开发光线 在活组织和可植入的设备中进行激发/感应，以进行光学致动。总体而言，TRD2将导致 一套光学系统，光学活性细胞系和高级生物反应器，以增强感应， 驱动，并控制组织工程系统。我们最初的重点将是生物发光和 光遗传学，其最终目标是开发光学兼容的细胞，生物材料和设备 与工程组织，体外和体内的接触。