Abstract
A limiting factor in large bone defect regeneration is the slow and disorganized formation of a functional vascular network in the defect area, often resulting in delayed healing or implant failure. To overcome this, strategies that induce angiogenic processes should be combined with potent bone graft substitutes in new bone regeneration approaches. To this end, we describe a unique approach to immobilize the pro-angiogenic growth factor VEGF165 in its native state on the surface of nanosized bioactive glass particles (nBGs) via a binding peptide (PR1P). We demonstrate that covalent coupling of the peptide to amine functional groups grafted on the nBG surface allows immobilization of VEGF with high efficiency and specificity. The amount of coupled peptide could be controlled by varying amine density, which eventually allows tailoring the amount of bound VEGF within a physiologically effective range. In vitro analysis of endothelial cell tube formation in response to VEGF-carrying nBG confirmed that the biological activity of VEGF is not compromised by the immobilization. Instead, comparable angiogenic stimulation was found for lower doses of immobilized VEGF compared to exogenously added VEGF. The described system, for the first time, employs a binding peptide for growth factor immobilization on bioactive glass nanoparticles and represents a promising strategy to overcome the problem of insufficient neovascularization in large bone defect regeneration.