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Orthopedic tissue engineering strategies have developed rapidly in response to large and growing clinical needs. However, current clinical methods for replacement of natural tissue function have significant limitations, and pragmatic challenges have hindered clinical use of emerging tissue engineering approaches. In addition, current methods are not yet capable of achieving complex spatial and temporal regulation of soluble signaling (e.g. growth factor signaling), which may be required for complex, functional tissue regeneration. We have begun to develop a series of new medical devices, which are designed to temporally and spatially regulate growth factor and cytokine signaling during tissue regeneration. The initial goal of these studies is to regulate the behavior of multipotent stem cells, and to promote formation of clinically relevant tissue interfaces (e.g. bone-tendon interfaces). The ultimate goal is to further understand and recapitulate the complex processes that lead to functional musculoskeletal development and regeneration.