Author:
Friend Nicole E.,Rioja Ana Y.,Kong Yen P.,Beamish Jeffrey A.,Hong Xiaowei,Habif Julia C.,Bezenah Jonathan R.,Deng Cheri X.,Stegemann Jan P.,Putnam Andrew J.
Abstract
AbstractRevascularization of ischemic tissues is a major barrier to restoring tissue function in many pathologies. Delivery of pro-angiogenic factors has shown some benefit, but it is difficult to recapitulate the complex set of factors required to form stable vasculature. Cell-based therapies and pre-vascularized tissues have shown promise, but the former require time for vascular assembly in situ while the latter require invasive surgery to implant vascularized scaffolds. Here, we developed cell-laden fibrin microbeads that can be pre-cultured to form primitive vascular networks within the modular structures. These microbeads can be delivered in a minimally invasive manner and form functional microvasculature in vivo. Microbeads containing endothelial cells and stromal fibroblasts were pre-cultured for 3 days in vitro and then injected within a fibrin matrix into subcutaneous pockets on the dorsal flanks of SCID mice. Vessels deployed from these pre-cultured microbeads formed functional connections to host vasculature within 3 days and exhibited extensive, mature vessel coverage after 7 days in vivo. Cellular microbeads showed vascularization potential comparable to bulk cellular hydrogels in this pilot study. Furthermore, our findings highlight some potentially advantageous characteristics of pre-cultured microbeads, such as volume preservation and vascular network distribution, which may be beneficial for treating ischemic diseases.
Funder
National Institute of Dental and Craniofacial Research
National Heart, Lung, and Blood Institute
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute of General Medical Sciences
Publisher
Springer Science and Business Media LLC
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