Tissue Engineering Resource Center

摘要 TRD2将专注于发展细胞系和先进的实时光学系统 工程组织的时空控制。细胞系将被基因工程改造为表达 用于定量和实时传感的生物发光蛋白质和用于光学的光遗传蛋白质 驱动力。假设是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 举止。与传统的生物反应器相结合，这些系统将实现自动化和 快速筛选多种参数的组织培养体系的优化 上下文。将追求三个具体目标。目标1：用于疾病的成像生物反应器 模特儿。骨转移性乳腺癌的组织工程模型将被用于优化 使用反馈控制回路实现化疗剂量的最大化和最小化 毒性。目的2：用于电刺激组织的反馈控制光生物反应器。vbl.使用 这一策略将使工程心脏和神经肌肉的定向刺激和成熟成为可能。 组织和研究心律失常的控制。目标3：生物反应器和植入式设备 厚重组织中的激发/感觉。这些能力将被用来开发用于 用于光学驱动的活体组织中的激发/传感和可植入装置。总体而言，TRD2将导致 一套光学系统，光学活性细胞系，以及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和 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接口。

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.