This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to solve the basic problem of tissue engineering and, for the first time, develop a perfused vascularized 3D myocardial tissue construct by using endothelialized porous synthetic tubes. This tissue construct could be used as an assay for drug testing; a new tool for cardiovascular research (for example, for studying the mechanism of stem cell recruitment); and finally, as a prototype for implantable tissue-engineered myocardial patches for treating cardiovascular diseases. We must accomplish following specific aims;: design a perfused mini-bioreactor;; design a porous tube with optimal, angio-permissive diameter of pores; develop technology for highly densely packed myocardial tissue in an hydrogel; endothelialize the porous tube and stimulate endothelial sprouts in the surrounding hydrogel; identify the optimal distance between tubes suitable for effective tissue vascularization through the sprouting of an endothelialized porous perfused tube, and finally generate a perfused, vascularized 3D myocardial tissue construct. During the reporting period, we accomplished successfully the first three specific aims submitted and published four papers in peer-reviewed journals. We designed and manufactured a chamber and assembled a perfused mini-bioreactor. It was shown that closely placed cell aggregates in a 3D hydrogel can fuse and form tissue constructs of desired geometrical form. We developed a novel method of centrifugal casting using an in-situ, cross-linkable, hyaluronic acid hydrogel, we were able to create highly densely packed myocardial tissue. Finally, using embryonic explants of quail brachiocephalic artery placed in a 3D collagen hydrogel, we have shown that endothelium can grow from an open end of the tube, and/or from an incised vascular wall, and form endothelial sprouts. Thus, the feasibility of using endothelial sprouts, originating from an endothelialized tube, for tissue vascularization has been at least partly validated.
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