Physical and Chemical Signals That Promote Vascularization of Capillary-Scale Channels
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Proper vascularization remains critical to the clinical application of engineered tissues. To engineer microvessels in vitro, we and others have delivered endothelial cells through preformed channels into patterned extracellular matrix-based gels. This approach has been limited by the size of endothelial cells in suspension, and results in plugging of channels below ~30 µm in diameter. Here, we examine physical and chemical signals that can augment direct seeding, with the aim of rapidly vascularizing capillary-scale channels. By studying tapered microchannels in type I collagen gels under various conditions, we establish that stiff scaffolds, forward pressure, and elevated cyclic AMP levels promote endothelial stability and that reverse pressure promotes endothelial migration. We applied these results to uniform 20-µm-diameter channels and optimized the magnitudes of pressure, flow, and shear stress to best support endothelial migration and vascular stability. This vascularization strategy is able to form millimeter-long perfusable capillaries within 3 days. Our results indicate how to manipulate the physical and chemical environment to promote rapid vascularization of capillary-scale channels within type I collagen gels.
KeywordsMicrovascular tissue engineering Collagen Endothelial cells Genipin Cyclic AMP Pressure
We thank Cliff Brangwynne and Marina Feric for access to their pipette puller, and Aimal Khankhel for assistance with experiments. This work was supported by Boston University through a Dean’s Catalyst Award (J.T.), a Lutchen Fellowship (R.M.L.), and awards from the Undergraduate Research Opportunities Program (R.M.L., N.F.B., G.C.). R.M.L. thanks Mr. and Mrs. William Felder for support through a Summer Term Alumni Research Scholarship at Boston University.
Conflicts of interest
Raleigh M. Linville, Nelson F. Boland, Gil Covarrubias, Gavrielle M. Price, and Joe Tien declare that they have no conflict of interest.
No human or animal studies were carried out by the authors for this article.
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