VEGF Release in Multiluminal Hydrogels Directs Angiogenesis from Adult Vasculature In Vitro

Abstract

Large bioengineered organs such as the heart and kidney need immediate perfusion by the host vascular network to avoid ischemia, support implant survival, and prevent implant failure. Vascularization of new bioengineered tissues can be stimulated by porous scaffold design and vascular growth factors. However, comprehensive vascularization of thick tissues in vitro remains a formidable challenge. We developed a simple and reproducible vascularization method that integrates a transparent biodegradable multiluminal scaffold for guided endothelial migration stimulated by intraluminal controlled release of Vascular Endothelial Growth Factor (VEGF). Two- and three-dimensional in vitro vasculogenesis induced by human umbilical vein endothelial cells (HUVEC)/fibroblast co-cultures formed discontinuous vessel-like structures. In sharp contrast, hydrogel microchannels with luminal collagen matrix, enticed the angiogenic growth from postnatal and adult aortic explants into the agarose microchannels, forming continuous vascular tubes identified by CD31 expression, in which the number of cells can be controlled by intraluminal VEGF concentration. This study suggests that multiluminal scaffolds can be used to promote angiogenesis from mature blood vessels and form vascular networks within thick bioengineered scaffolds. This method might offer a viable alternative in the prevascularization of bio-artificial organs.