Combinatorial effect of nano whitlockite/nano bioglass with FGF-18 in an injectable hydrogel for craniofacial bone regeneration

Abstract

Functional regeneration of bone defects, especially critical-sized, in the craniofacial region remains a major clinical challenge that needs intervention. To address this, the present work focuses on the development of an injectable chitin–PLGA hydrogel (CG) containing bioglass nanoparticles (nBG) or whitlockite nanoparticles (nWH) with FGF-18, and compares the osteogenic and neo-bone formation potential against commercially available hydroxyapatite nanoparticles (nHAP) with FGF-18 fortified CG hydrogel in the critical-sized defect region. The developed CG was injectable and the incorporation of bio-ceramics didn't affect the injectability. Sustained release of FGF-18 was achieved in bio-ceramic containing CG hydrogel systems, while CG hydrogel alone displayed rapid release. In addition, the nBG or nWH containing CG hydrogel groups showed in vitro angiogenic potential. Furthermore, ALP activity, BMP-2 quantification and osteogenic gene expression assays were conducted to ascertain the osteogenic differentiation potential of the hydrogels. In the combination groups, CGnWHF (nWH + FGF-18 containing CG) showed highest osteogenic potential with a synergistic effect, compared to all other groups studied. In vivo bone regeneration studies displayed near-complete bone regeneration for CGnWHF, where its BV/TV% was the highest (synergistic effect) compared to CGnBGF (nBG + FGF-18 in CG) and nHAP with FGF-18 (additive effect) after 8 weeks of implantation. Thus, the use of CGnWHF in irregular craniofacial bone defects could be an attractive option.