Co-culture of human umbilical vein endothelial cells and human bone marrow stromal cells into a micro-cavitary gelatin-methacrylate hydrogel system to enhance angiogenesis

Vascular tissue engineering seeks to develop functional blood vessels that comprise of both endothelial cells and pericytes for translational medicine and is often faced with numerous challenges such as nutrients and wastes diffusion problem in the centre of the scaffolds. Various strategies have been adopted to solve the diffusion problem in thick engineered scaffolds. Typically, microchannels or dissolvable microspheres are introduced into three-dimensional (3D) scaffolds as an alternative way to improve the infiltration of scaffolds and endothelial cells are usually incorporated into the biomaterials. While some research groups now focus on finding supporting cells to build further vascularized structures in the scaffolds. In this study, a bioinspired 3D gelatin-methacrylate (Gel-MA) hydrogel with dissolvable microspheres was created to encapsulate human bone marrow stromal cells (HMSCs) and human umbilical vein endothelial cells (HUVECs) which was used to investigate whether HMSCs could play a pericytes-like role and enhance vascularization within the engineered scaffolds. The results showed co-culture of HMSCs and HUVECs demonstrated significantly improved vascularization when compared to either HUVECs or HMSCs monoculture. Angiogenic genes were expressed significantly higher in co-culture group. Moreover, when implanting the pre-vascularized scaffolds in vivo, co-culture system integrated more successfully with host tissue and showed higher host tissue invasion than any other groups. More importantly, both the qPCR and immunofluorescence results indicated MSCs differentiated towards pericytes to enhance vascularization in this study. This paper highlights the enhanced capability of 3D micro-cavitary Gel-MA hydrogel for co-culturing HUVECs and HMSCs to promote vascularization which presents a potential strategy for future tissue repair and regeneration.