Collagen Functionalized With Graphene Oxide Enhanced Biomimetic Mineralization and In Situ Bone Defect Repair.

Biomimetic mineralization using simulated body fluid (SBF) can form a bone-like apatite (Ap) on the natural polymers and enhance osteoconductivity, biocompatibility and reduce immunological rejection. Nevertheless, the coating efficiency of bone-like apatite layer on natural polymers is still needed to be improved. Graphene oxide (GO) is rich in functional groups, such as carbonyls (-COOH) and hydroxyls (-OH), which can provide more active sites for biomimetic mineralization and improve the proliferation of the rat bone marrow stromal cells (r-BMSCs). In this study, we introduced 0% W/V, 0.05% W/V, 0.1% W/V and 0.2% W/V concentrations of GO into collagen (Col) scaffolds and immersed the fabricated scaffolds into SBF for 1, 7 and 14 days. In vitro environment scanning electron microscopy (ESEM), energy dispersive spectrometer (EDS), thermogravimetric analysis (TGA), micro CT, calcium quantitative analysis and cellular analysis were used to evaluate the formation of bone-like apatite on the scaffolds. In vivo implantation of the scaffolds into the rat cranial defect was used to analyse the bone regeneration ability. The resulting GO-Col-Ap scaffolds exhibited a porous and interconnected structure coated with a homogeneous distribution of bone-like apatite on their surfaces. Ca/P ratio of 0.1% GO-Col-Ap group was equal to that of natural bone tissue based on EDS analysis. More apatites were observed in 0.1% GO-Col-Ap group through TGA analysis, micro CT evaluation, and calcium quantitative analysis. Furthermore, the 0.1% GO-Col-Ap group showed significantly higher r-BMSCs adhesion and proliferation in vitro and more than two-fold higher bone formation than Col-Ap group in vivo. Our study provides a new approach of introducing graphene oxide into bone tissue engineering scaffolds to enhance biomimetic mineralization.