Self-assembled nanocomposite hydrogels enhanced by nanoparticles phosphonate-magnesium coordination for bone regeneration

The repair of critical-sized bone defects remains challenging. Natural polysaccharide-based hydrogels (NPHs) have shown great promise for facilitating bone defect healing, but limited by osteogenesis, mechanical strength and stability. Here we prepared a water-soluble methacrylic anhydride-co-phosphate modified chitosan (CSMAP) incorporated MgO nanoparticles to form a pergel, and followed by introduction of acrylamide to construct a double-network hydrogel (CSMAP-MgO). We found that Mg2+ released from CSMAP-MgO hydrogel in a stable and sustained manner in 30 days and the compressive strength was maintained and the compressive modulus was even enhanced during immersion in PBS for 28 days. Moreover, the CSMAP-MgO hydrogel was superior in promoting in vitro calcium phosphate deposition, MC3T3-E1 cell proliferation, osteogenic differentiation, and mineralization compared to Magnesium free groups. At 12 weeks post-implantation into a rat critical-sized calvarial defect, the CSMAP-MgO hydrogel promoted significantly more new bone formation compared to CSMAP and non-treated groups. Thus, the CSMAP-MgO hydrogel has great promising as a bone filling material.