CORE -- TISSUE ENGINEERING BIOREACTOR

工程化组织的临床最终科学效用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。这一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，给予多种物理刺激，并能够在不同层次尺度上对细胞和组织进行实时成像。骨软骨(软骨/骨)组织和心肌被选为截然不同的、临床相关的工程组织的范例，作为生物反应器开发和验证的模型。将建立两个不同的生物反应器系统：一个是机械刺激(用于工程化骨软骨组织)，另一个是电刺激(用于工程心肌)。我们设想在这一核心中有三个相互关联的研究领域： 1.利用非破坏性成像方法(荧光显微镜、频域光学成像、核磁共振、超声和多层螺旋CT)，工程构建物将被用作可控组织模型，用于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“仿生”功能组织工程协议的发展。 3.将在体外和动物模型中分析组织组装的进展和工程化构造的功能。 我们在以前的研究中建立的数学模型将进一步扩展到分析 并建立了环境因素之间的相关关系， 结构和功能组织特性。总体而言，酷睿3的设计是为了形成 在软骨、骨对照研究中回答基本生物学问题的基础 和心肌。

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.