Recovery of Therapeutically Ablated Engineered Blood-Vessel Networks on A Plug-And-Play Platform.

Limiting the availability of key angiogenesis-promoting factors is a successful strategy to ablate tumor-supplying blood vessels or to reduce excessive vasculature in diabetic retinopathy. However, the efficacy of such anti-angiogenic therapies (AATs) varies with tumor type, and regrowth of vessels has been observed upon termination of treatment. Our ability to understand and develop AATs remains limited by a lack of robust in vitro systems for modeling the recovery of vascular networks. Here, we engineer complex three-dimensional micro-capillary networks by sequentially seeding human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) and human umbilical vein endothelial cells (HUVECs) on a previously established, synthetic plug-and-play hydrogel platform. In the tightly interconnected vascular networks that form this way, the two cell types share a basement membrane-like layer and can be maintained for several days of co-culture. Pre-formed networks degrade in the presence of bevacizumab. Upon treatment termination, vessel structures grow back in their original positions after replenishment with new endothelial cells, which also integrate into unperturbed established networks. Our data suggests that this plug-and-play platform enables the screening of drugs with blood-vessel inhibiting functions. We believe that this platform could be of particular interest in studying resistance or recovery mechanisms to AAT treatment. This article is protected by copyright. All rights reserved.