Engineering Complex, Spatially-patterned Tissue Structures from Stem Cells

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Roy/ 1159326 In the past decade significant advances have been made in stem cell differentiation to create engineered tissues. However, most efforts to date have focused on regenerating a homogenous tissue structure whose bulk properties are similar to that of native tissues. But, most human tissues are complex, both structurally and functionally, and possess spatially-varying compositions and mechanical properties. Directing stem cells into such mature, three-dimensionally organized, complex tissues has not yet been achieved. A model example is articular cartilage, which has been widely studied in tissue engineering for several decades. Anatomically and functionally, articular cartilage consists of four, spatially distinct regions; the superficial, transitional, deep, and calcified zones. Each zone is characterized by unique extra-cellular matrix compositions, mechanical properties and cellular organization. Classical tissue engineering approaches for creating homogenous tissue replacements for articular cartilage has failed to achieve widespread clinical effectiveness because the engineered bulk properties do not mimic native tissue function. Based on recent findings that unique material compositions can be used to direct stem cells into specific types of chondrocytes that correspond to those from the various zones of articular cartilage, this project will explore a unique multi-layered hydrogel constructs with spatially varying biomaterial-niches for simultaneously differentiating a single stem cell population into a complex articular cartilage. The knowledge gathered would provide new insights on the feasibility of engineering complex, functionally-relevant tissues whose mechanical properties and composition can vary spatially.