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Drug Deliv Transl Res. 2015 Apr;5(2):75-88. doi: 10.1007/s13346-012-0122-y.

Controlled protein delivery in the generation of microvascular networks.

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Department of Biomedical Engineering, Yale University, New Haven, CT 06511.
Department of Medicine and Section of Nephrology, Yale University School of Medicine, New Haven, CT 06520.
Departments of Immunobiology, Pathology, and Dermatology, Yale University School of Medicine, New Haven, CT 06520.


Rapid induction and stabilization of new microvascular networks is essential for the proper functioning of engineered tissues. Many efforts to achieve this goal have used proangiogenic proteins-such as vascular endothelial growth factors-to induce the formation of new microvessels. These proteins have demonstrated promise in improving vascularization, but it is also clear that the spatial and temporal presentation of these signals is important for achieving proper vascular function. Delivery systems that present proteins in a localized and sustained manner, can promote the formation and stabilization of microvascular networks by precisely presenting proangiogenic proteins at desired locations, and for specified durations. Further, these systems allow for some control over the sequence of release of multiple proteins, and it has become clear that such coordination is critical for the development of fully functional and mature vascular structures. This review focuses on the actions of proangiogenic proteins and the innovations in controlled release technologies that precisely deliver these to stimulate microvascular network formation and stabilization.


angiogenesis; microvascular network; protein delivery; stabilization; tissue engineering; vascularization

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