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Feedback mechanisms are critical components of many pro-angiogenic signaling pathways that keep vessel growth within a functional range. The Vascular Endothelial Growth Factor-A (VEGF-A) pathway utilizes the decoy VEGF-A receptor Flt-1 to provide negative feedback regulation of VEGF-A signaling. In this study, we investigated how the genetic loss of flt-1 differentially affects the branching complexity of vascular networks in tissues despite similar effects on endothelial sprouting. We selectively ablated flt-1 in the post-natal retina and found that maximum induction of flt-1 loss resulted in alterations in endothelial sprouting and filopodial extension, ultimately yielding hyper-branched networks in the absence of changes in retinal astrocyte architecture. The mosaic deletion of flt-1 revealed that sprouting endothelial cells flanked by flt-1−/− regions of vasculature more extensively associated with underlying astrocytes and exhibited aberrant sprouting, independent of the tip cell genotype. Overall, our data support a model in which tissue patterning features, such as retinal astrocytes, integrate with flt-1-regulated angiogenic molecular and cellular mechanisms to yield optimal vessel patterning for a given tissue.

in Wiley Online Library (wileyonlinelibrary.com).Fluid dynamics and heat transfer of flow through periodic open-cellular microlattice structures are characterized for varying superficial flow orientations and flow rates to investigate heat transfer and pressure loss anisotropy. For given Reynolds number, friction factor is lowest when flow is aligned with the largest straight-through passages in the microlattice. A maximum friction factor, over twice the optimally aligned friction factor, exists for flow orientations between /8 and /4 rad off the optimal alignment, with little variation in friction factor for /8 and /4 rad. Heat transfer is maximized at /4 rad off axis from the largest straight-through passages; however, less angular variation occurs in Nusselt number than in friction factor. Empirical correlations involving superellipses yield analytical equations describing Nusselt number dependence on flow angle and Reynolds number. This work enables selection of optimal flow orientations and optimal cellular architecture in convective heat transfer implementations of microlattice materials for lightweight and multifunctional applications.