Spatially controlled rhBMP-2 mediated calvarial bone formation in a transgenic mouse model

The study aimed to investigate the localized osteogenic activity of recombinant human bone morphogenetic protein (rhBMP-2), when delivered using enzymatically crosslinkable injectable glycol chitosan hydrogel. A critical sized bilateral calvarial defect model was used wherein one defect was implanted with rhBMP-2 loaded hydrogel (HPP-GC + BMP). The neighboring defect was implanted with an osteoconductive, collagen hydroxyapatite matrix Healos (R). The implantation of HPP-GC + BMP led to complete closure of the critical sized defect at 4 weeks post-implantation. The neighboring site implanted with Healos (R) however, did not show any bone formation. The spatial control of rhBMP-2 bioactivity at the cellular level was confirmed by histological and histomorphometric analysis of the calvaria isolated from Co13.6 transgenic animals which can express fluorescence in osteoblast and pre-osteoblast cells. The retained rhBMP-2 in HPPGC+ BMP implant was able to localize osteoprogenitor recruitment and osteogenesis, at the implantation site. The results demonstrate the efficacy of HPP-GC hydrogel in minimizing the diffusive loss of rhBMP-2 from the implantation site, compared to the collagen hydroxyapatite scaffold. (C) 2017 Elsevier B.V. All rights reserved.