Tissue Engineering Resource Center

组织工程资源中心

基本信息

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
项目类别：
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

项目摘要

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将专注于实时细胞系和先进光学系统的开发工程组织的时空控制。细胞系将经过基因工程改造以表达用于定量和实时传感的生物发光蛋白，以及用于光学的光遗传学蛋白驱动。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范围内对工程组织进行实时反馈控制方式。与传统的生物反应器相结合，这些系统将实现自动化和组织培养系统的优化能够快速筛选各种参数上下文。将追求三个具体目标。目标 1：用于疾病的成像生物反应器造型。骨转移性乳腺癌的组织工程模型将用于优化使用反馈控制回路来确定化疗剂量，以最大限度地提高疗效并最大限度地减少毒性。目标 2：具有反馈控制的用于电兴奋组织的光遗传学生物反应器。使用通过这一策略，我们将实现工程心脏和神经肌肉的定向刺激和成熟组织并研究心律失常的控制。目标 3：生物反应器和植入式设备厚组织中的激发/传感。这些能力将用于开发光导管活体组织和用于光学驱动的植入设备中的激发/传感。总体而言，TRD2 将导致一套光学系统、光学活性细胞系和先进的生物反应器，用于增强传感，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、生物材料和设备与体外和体内工程组织的界面。