A multifunctional nanocomposite hydrogel with controllable release behavior enhances bone regeneration

Autologous and allogeneic bone grafts remain the gold standard for repairing bone defects. However, donor shortages and postoperative infections contribute to unsatisfactory treatment outcomes. Tissue engineering technology that utilizes biologically active composites to accelerate the healing and reconstruction of segmental bone defects has led to new ideas for in situ bone repair. Multifunctional nanocomposite hydrogels were constructed by covalently binding silver (Ag(+)) core-embedded mesoporous silica nanoparticles (Ag@MSN) to bone morphogenetic protein-2 (BMP-2), which was encapsulated into silk fibroin methacryloyl (SilMA) and photo-crosslinked to form an Ag@MSN-BMP-2/SilMA hydrogel to preserve the biological activity of BMP-2 and slow its release. More importantly, multifunctional Ag(+)-containing nanocomposite hydrogels showed antibacterial properties. These hydrogels possessed synergistic osteogenic and antibacterial effects to promote bone defect repair. Ag@MSN-BMP-2/SilMA exhibited good biocompatibility in vitro and in vivo owing to its interconnected porosity and improved hydrophilicity. Furthermore, the multifunctional nanocomposite hydrogel showed controllable sustained-release activity that promoted bone regeneration in repairing rat skull defects by inducing osteogenic differentiation and neovascularization. Overall, Ag@MSN-BMP-2/SilMA hydrogels enrich bone regeneration strategies and show great potential for bone regeneration.