Tissue Engineering Resource Center

组织工程资源中心

• 批准号: 10683746
• 负责人: Gordana Vunjak-Novakovic
• 金额: $ 41.04万
• 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/10683746
• 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; Implant; 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; Therapeutic; Thick; Time; Tissue Engineering; Tissue constructs; Tissues; Toxic effect; Transgenic Organisms; Work; biological systems; bioluminescence imaging; 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; waveguide

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.

总结 TRD 2将专注于开发细胞系和先进的实时光学系统。 工程组织的时空控制。细胞系将通过基因工程来表达 用于定量和实时传感的生物发光蛋白，以及用于光学成像的光遗传蛋白。 驱动。假设表达这些蛋白质的转基因组织与 先进的光学系统将能够在时空中对工程组织进行实时反馈控制， 方式结合传统的生物反应器，这些系统将允许自动化和 优化组织培养系统，能够快速筛选多种参数， contexts.将追求三个具体目标。目标1：用于疾病的成像生物反应器 建模将使用骨转移性乳腺癌的组织工程模型来优化 使用反馈控制回路来最大化功效和最小化化疗剂量。 毒性目的2：具有反馈控制的用于电可兴奋组织的光遗传生物反应器。使用 这一策略将使定向刺激和成熟的工程心脏和神经肌肉 研究心律失常的控制。目标3：生物反应器和植入式器械 在厚组织中的激发/感测。这些能力将用于开发光导管， 在活体组织中的激发/感测以及用于光学致动的可植入装置。总体而言，TRD 2将导致 一套光学系统、光学活性细胞系和用于增强传感的先进生物反应器， 组织工程系统中的驱动和控制。我们最初的重点将是生物发光， 光遗传学，最终目标是开发光学兼容的细胞，生物材料和设备， 在体外和体内与工程组织的界面。