CORE -- TISSUE ENGINEERING BIOREACTOR

核心——组织工程生物反应器

• 批准号: 7476330
• 负责人: Gordana Vunjak-Novakovic
• 金额: $ 72.05万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 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/7476330
• 关键词: Address; Animal Model; Anisotropy; Area; Behavior; Biochemical; Biocompatible Materials; Biological; Biomimetics; Bioreactors; Bone Tissue; Bone and Cartilage Funding; Cartilage; Cell Differentiation process; Cell physiology; Cells; Clinical; Compatible; Computers; Controlled Study; Culture Media; Data; Development; Electric Stimulation; Engineering; Environment; Environmental Risk Factor; Fluorescence Microscopy; Frequencies; Gene Proteins; Genetic; Goals; Image; In Situ; In Vitro; Individual; Intercellular Fluid; Kinetics; Magnetic Resonance Imaging; Measures; Mechanical Stimulation; Mechanics; Methods; Minerals; Modeling; Monitor; Myocardium; Optics; Property; Protocols documentation; Rate; Research; Signal Transduction; Spectrum Analysis; Stem cells; Stimulus; System; Time; Tissue Engineering; Tissue Model; Tissues; Validation; Video Microscopy; base; bone; bone engineering; cellular imaging; clinically relevant; density; design; fluid flow; in vivo; interstitial; mathematical model; novel; optical imaging; osteochondral tissue; protein expression; response; scaffold; tissue culture; tomography

Clinical end scientific utility of engineered tissues critically depends on our ability to direct and modulate cell differentiation and functional tissue assembly, in vitro and in vivo. The focus of this core will be on the development and utilization of novel bioreactors designed to precisely control the cellular microenvironment, impart multiple physical stimuli, and enable real time imaging of cells and tissues at various hierarchical scales. Osteochondral (cartilage/bone) tissues and myocardium are selected as paradigms of distinctly different, clinically relevant engineered tissues to serve as models for bioreactor development and validation. Two different bioreactor systems will be established: one with mechanical stimulation (for engineering osteochondral tissues) and one with electrical stimulation (for engineering myocardium). We envision three interrelated areas of research in this core: 1. Engineered constructs will be used as controllable tissue models for studies of cell responses to genetic and environmental factors using nondestructive imaging methods (fluorescence microscopy, frequency-domain optical imaging, MRI, ultrasound and mu CT). 2. The obtained information will drive the development of "biomimetic" protocols for functional tissue engineering. 3. The progression of tissue assembly and the functionality of engineered constructs will be analyzed in vitro and in animal models. Mathematical models developed in our previous studies will be further extended to analyze the kinetic and transport rates and establish correlations between the environmental factors, structural and functional tissue properties. Overall, Core 3 has been designed to form the basis for answering fundamental biological questions in controlled studies of cartilage, bone and myocardium.

工程化组织的临床和科学用途关键取决于我们在体外和体内指导和调节细胞分化和功能组织组装的能力。该核心的重点将是开发和利用新型生物反应器，旨在精确控制细胞微环境，赋予多种物理刺激，并使细胞和组织在各种层次尺度上的真实的时间成像。选择骨软骨（软骨/骨）组织和心肌作为明显不同的临床相关工程组织的范例，以用作生物反应器开发和验证的模型。将建立两种不同的生物反应器系统：一种具有机械刺激（用于工程化骨软骨组织），另一种具有电刺激（用于工程化心肌）。我们设想在这个核心研究三个相互关联的领域： 1.工程构建体将用作可控组织模型，用于使用非破坏性成像方法（荧光显微镜、频域光学成像、MRI、超声和μ CT）研究细胞对遗传和环境因素的反应。 2.所获得的信息将推动功能性组织工程的“仿生”方案的发展。 3.将在体外和动物模型中分析组织组装的进展和工程构建体的功能。 在我们以前的研究中开发的数学模型将进一步扩展到分析 动力学和传输速率，并建立环境因素之间的相关性， 结构和功能组织特性。总体而言，Core 3旨在形成 在软骨、骨的对照研究中回答基本生物学问题的基础 和心肌。