Investigation of Integrated Effects of Hydroxyapatite and VEGF on Capillary Morphogenesis of Endothelial Cells

ACS Appl Bio Mater. 2019 Jun 17;2(6):2339-2346. doi: 10.1021/acsabm.8b00780. Epub 2019 Jun 4.

Abstract

Major drawbacks of using autografts and allografts for repairing large bone defects/injuries are the shortage of available tissues and potential disease transmission. Bone tissue engineering is believed to be a promising alternative to bone grafts. The concomitant formation of vascular networks within the tissue engineered constructs for successful bone regeneration still remains a challenge. The physicochemical properties of a tissue microenvironment are known to regulate vascular network formation. However, our understanding of the mechanism, by which endothelial cells integrate these physicochemical signals emanating from the microenvironment to undergo capillary morphogenesis, is limited. In this study, the integrated effects of the vascular endothelial growth factor (VEGF), pro-angiogenic molecule, and hydroxyapatite (HA), widely used as an additive and a scaffold in bone reconstructive surgery, on capillary formation of human umbilical vein endothelial cells (HUVECs) were investigated. Toward this, HUVECs were seeded on scaffolds composed of 15% (w/v) poly(ethylene glycol) diacrylate, 5% (w/v) gelatin methacrylate (GelMA), and 1% (w/v) photoinitiator. The concentration of HA was varied from 0% to 0.2% (w/v). The study demonstrated that HA elicited an inhibitory response. The presence of VEGF promoted a sprouting response with a significant enhancement in the number of sprouts observed in the case of gels with higher concentrations of HA.

Keywords: VEGF; bone tissue engineering; endothelial cells; gelatin methacrylate; hydroxyapatite; sprouting.