Short-term delivery of fibrin-bound VEGF protein in osteogenic grafts: increased vascularization with efficient bone formation (original) (raw)

The major challenge for biomaterials in bone regeneration is a good integration with the host tissue, in which a proper vasculatization is crucial. Calcium phosphate (CP) materials have gain importance in bone regeneration since it has been proved that they stimulate the formation of bone. However, little is known about their angiogenic potential. Recent findings in our group suggest that Ca 2+ have a role in angiogenesis 1,2,3. In this study we developed different Ca 2+ releasing scaffolds by combining different sol-gel CP degradable nanoparticles (containing only Ca and P) with electrospun polylactic acid (PLA) nanofibers. Scaffolds were seeded with human mesenchymal stem cells (hMSCs) and cultured in both regular (RM) and osteogenic (OM) media. Cell proliferation, Alkaline Phosphatase (ALP) activity, VEGF synthesis and L-lactate release were assessed. Angiogenesis was examined in vitro by HUVEC tube formation and in vivo by using the chick choriallantoic membrane (CAM) angiogenic model. Scaffolds showed a long term (up to 20 days) Ca 2+ release in both culture media. The presence of the particles in the scaffolds enhanced hMSCs adhesion and increased their proliferation as well as the ALP activity in OM. hMSCs substantially increased their production of L-lactate and VEGF when seeded on the scaffolds containing the particles in RM. However, this increase was minimized when cultured in OM. HUVEC showed an enhancement in tube formation when cultured in the conditioned media obtained from culturing the hMSCs on the scaffolds. This time, no differences were found between the scaffolds with or without particles. Finally, the CAM assay showed a significant increase in the formation of new blood vessels for the scaffolds containing the particles. Their angiogenic response was similar to a VEGF loaded PLA fibers used as a positive control. We demonstrate that the presence of the Ca 2+ releasing particles enhanced several angiogenic parameters. However, some of these parameters were significantly reduced in OM due to the osteogenic differentiation of hMSCs.