CORE -- TISSUE ENGINEERING BIOREACTOR

工程组织的临床最终科学效用严重依赖于我们在体外和体内指导和调节细胞分化和功能性组织组装的能力。该核心的重点将是开发和利用新型生物反应器，以精确控制细胞微环境，传递多种物理刺激，并在各种层次尺度上实现细胞和组织的实时成像。骨软骨（软骨/骨）组织和心肌被选择作为明显不同的范例，临床相关的工程组织作为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：一种是机械刺激（用于工程骨软骨组织），另一种是电刺激（用于工程心肌）。我们设想在这个核心中有三个相互关联的研究领域：

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.