This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Tissue engineering holds enormous potential to replace or restore function to a wide range of tissues. However, despite advances in materials for scaffolding, and stem cell preservation and differentiation, the most successful applications have continued to be in thin (<2 mm) avascular tissues in which delivery of essential nutrients occurs primarily by diffusion. More complex organs or thicker connective tissue (>1cm) will only survive when implanted if the tissue is rapidly vascularized, thereby ensuring that all cells receive an adequate supply of oxygen and nutrients. The development of thick tissues beyond the diffusion limitation remains, perhaps, the greatest challenge facing the field of tissue engineering. The past decade has brought tremendous advances in our understanding of new blood vessel formation, providing a rich environment for innovative designs of vascularized thick implantable tissues. Engineered tissues seeded with both stromal and endothelial cells have been shown to form an extensive interconnected vascular network in vitro. Prevascularized tissues, such as these, can then be implanted into a host and subsequently form functional junctions with the host circulation. This results in very rapid perfusion of potentially thick engineered tissues. When combined with Wide Field Functional Imaging (WiFI) to measure changes in implant perfusion and metabolism, these strategies stand to overcome the most significant impediments in the field of tissue engineered.
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