There is a significant rise in the bone grafts demand worldwide to treat bone defects owing to continuous increase in conditions such as injury, trauma, diseases, or infections. Therefore, development of three-dimensional scaffolds has evolved as a reliable technology to address the current limitations for bone tissue regeneration. Mimicking the natural bone, in this study, we have designed a silk fibroin/hydroxyapatite scaffold inlaid with a bioactive phytochemical (quercetin) at different concentrations for promoting osteogenesis, especially focusing on quercetin ability for enhancing bone health. Characterization of the quercetin/silk fibroin/hydroxyapatite (Qtn/SF/HAp) scaffolds showed an increased pore size and irregular porous microstructure with good mechanical strength. The Qtn (low-content)/SF/HAp scaffold was found to be an efficient cell carrier facilitating cellular growth, osteogenic differentiation, and proliferation as compared to SF/HAp and Qtn (high-content)/SF/HAp scaffolds. However, Qtn (high-content)/SF/HAp was observed to inhibit cell proliferation without any effects on cell viability. In vitro and in vivo outcomes studied using bone marrow-derived mesenchymal stem cells (rBMSCs) confirm the cytocompatibility, osteogenic differentiation ability, and prominent upregulation of the bone-specific gene expressions for the rBMSCs-seeded Qtn/SF/HAp scaffolds. In particular, the implanted Qtn (low-content)/SF/HAp scaffolds at the bone defect site were found to be well-attached and amalgamated with the surrounding tissues with approximately 80% bone volume recovery at 6 weeks after surgery as compared with other groups. Based on the aforementioned observations highlighting the quercetin efficiency for bone regeneration, the as-synthesized Qtn (low-content)/SF/HAp scaffolds can be envisioned to provide a biomimetic bone-like microenvironment promoting rBMSCs differentiation into osteoblast, thus suggesting a potential alternative graft for high-performance regeneration of bone tissues.
