Phosphocreatine-modified chitosan porous scaffolds promote mineralization and osteogenesis in vitro and in vivo

Abstract By mimicking the role of phosphate groups in native tissues and encouraging tissue formation, phosphate-functionalized biopolymers have been widely employed to accelerate the formation of bone injury. In this study, phosphocreatine is screened as a phosphate source and applied in the preparation of phosphocreatine-modified chitosan (CS-P) and porous scaffolds. CS-P exhibits much better hydrophilicity, solubility, protein adsorption and mineralization than pure chitosan (CS). Meanwhile, in comparison to CS scaffold, the CS-P scaffold significantly enhances the in vitro osteogenic differentiation of hFOB cells, indicated by the higher alkaline phosphatase (ALP) activity, denser mineralization deposition and up-regulated osteogenesis-related genes including runt-related transcription factor-2, ALP, osteocalcin and osteopontin at both mRNA and protein levels. The in vivo results indicate an enhancing effect of the CS-HP scaffold on the bone regeneration ability. We further confirm that phosphocreatine modification promotes the osteogenic differentiation of hFOB cells by activating the MAPK signalling pathway. The phosphocreatine-modified chitosan holds great potential for bone repair and regeneration.