Inosculation potential of angiopoietin-4-immobilized pHEMA-based bone scaffolds

Abstract

Although angiopoietin-1has potential therapeutic use in angiogenesis, the biological role of angiopoietin-4, especially in its immobilized form, is already unknown. In this study, vascularization potential of angiopoietin-4 either alone or in combination with vascular endothelial growth factor (VEGF) was investigated following its immobilization onto the poly(2-hydroxyethyl methacrylate)-based bone scaffolds. Poly(2-hydroxyethyl methacrylate) (pHEMA)-based superporous hydrogels (SPHs) were synthesized by radical polymerization of hydroxyethyl methacrylate in the presence of gelatin or chitosan and the porosity was achieved by gas foaming. However, only pHEMA-gelatin SPHs fulfill the structural and biological characteristics of a bone scaffold. Therefore, angiopoietin-4 and/or VEGF were immobilized successfully onto the pHEMA–gelatin SPHs using carbodiimide chemistry. The cell culture studies that were performed with human umbilical vein endothelial cells (HUVECs) for 28 days showed that immobilized angiopoietin-4 supported sprout formation more than that of other groups, while the immobilized VEGF including scaffolds promoted proliferation of HUVECs.