The purpose of this study was to evaluate the
glucose cross-linked
gelatin/
zein scaffolds for bone regeneration in vitro and in vivo. The nanofibrous scaffolds exhibited fast mineralization in the concentrated simulated body fluid with the deposited
octacalcium phosphate and
dicalcium phosphate dehydrate. The nanofibrous scaffolds exhibited no cytotoxic effect on MC3T3e1 cells in a
CCK-8 test. Additionally, scanning electron microscope and confocal
laser scanning microscopy images revealed that all the scaffolds were biocompatible and showed excellent support for MC3T3e1 cells. In the osteogenesis characterizations,
Alizarin Red staining experiments indicated the improved
calcium deposits on the cross-linked scaffolds, while the
alkaline phosphatase activity showed no difference. Furthermore, the in vivo cranial bone regeneration results suggested that the cross-linked
gelatin/
zein scaffolds presented a strong positive effect on the cranial bone regeneration with the increased new bone volume and connective tissue formation, but the incorporation of
zein in the
gelatin scaffolds did not favor the bone regeneration. Moreover, the cross-linked
gelatin scaffold retarded the
bone resorption as indicated by the higher levels of IFN-γ and lower levels of
IL-6, which restricted the differentiation of osteoclasts.