Sustained release of chrysin from chitosan-based scaffolds promotes mesenchymal stem cell proliferation and osteoblast differentiation

•The bioavailability and osteogenic effects of chrysin, a natural flavonoid, were investigated.•Chrysin was incorporated at different concentrations into biocomposite scaffolds.•Chrysin-containing scaffolds were not cytotoxic to mouse mesenchymal stem cells.•Chrysin released from scaffolds stimulated cell proliferation.•Chrysin released from scaffolds promoted osteoblast differentiation. Numerous phytochemical compounds have recently been reported to stimulate osteogenesis. In this study, the bioavailability and osteogenic effects of chrysin, a natural flavonoid, were investigated. Chrysin was incorporated at different concentrations into biocomposite scaffolds containing carboxymethyl cellulose, chitosan, and nano-hydroxyapatite, through the freeze-drying method. The physicochemical and material characteristics of chrysin-incorporated scaffolds were investigated, and chrysin had no effect on them. These chrysin-containing scaffolds were not cytotoxic to mouse mesenchymal stem cells (mMSCs). Chrysin released from scaffolds stimulated cell proliferation and promoted osteoblast differentiation. Osteoblast differentiation enhanced by chrysin from scaffolds could be due to downregulation of co-repressors of the osteoblast differentiation transcription factor Runx2 in these cells. Thus, chrysin release from scaffolds has potential effects on proliferation and differentiation of mMSCs; hence, it has potential application in bone tissue engineering.