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.
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