Calcium phosphate bone cements, functionalized with VEGF: release kinetics and biological activity

Calcium phosphate bone cements are of great interest for bone replacement since the nanocrystalline structure allows their remodelling into native bone tissue. A strategy to accelerate vascularization of the implant region is the functionalization with vascular endothelial growth factor (VEGF), which is known to mediate angiogenesis in vivo. In this study, the release of recombinant human VEGF (rhVEGF(165)) following physical adsorption to Biocement D (BioD) and several modifications were investigated. Our data demonstrate a high VEGF binding capacity of BioD and a sustained release with a moderate initial burst. A proliferation assay using endothelial cells revealed maintenance of biological activity of VEGF after release from BioD. Release behavior of BioD was not improved by modification with mineralized collagen type I, as well as with a combination of mineralized collagen with O-phospho-L-serine and sodium citrate, respectively. In contrast, a positive impact of these modifications on the activity of released VEGF was observed; in case of the phosphoserine- and sodium citrate-modified cements, the biological efficacy of released VEGF was even higher than that of nonreleased control VEGF. We conclude that the bone implant material BioD and, especially, the phosphoserine modification may support activation of angiogenesis by delivery of VEGF in a local and sustained manner.