Multifunctional enzymatically crosslinked hyaluronic acid/gelatin/mesoporous bioactive glass nanocomposite hydrogel as an alendronate carrier for treating osteoporotic fractures.

This study presents an injectable nanocomposite hydrogel composed of hyaluronic acid, gelatin, and amine-functionalized mesoporous bioactive glass nanoparticles (AMBGs) for localized delivery of alendronate (ALN). Enzymatically cross-linked hyaluronic acid/gelatin hydrogels (HG) were prepared following the modification of hyaluronic acid and gelatin with tyramine. Nanocomposite hydrogels (HGB) were fabricated by incorporating varying concentrations of AMBGs into the HG hydrogel. Adding AMBGs significantly influenced the physical and biomechanical properties of the hydrogels. The hydrogel containing 0.5 % AMBGs (HGB-0.5 %) exhibited the highest compressive strength compared to the other formulations. The bioactivity and osteo-conductive properties of HGB-0.5 % hydrogel were confirmed by forming an apatite-like layer on the hydrogel surface after incubation in simulated body fluid and an ion release test. ALN was loaded into the HGB-0.5 % hydrogels with varying concentrations, and the biological activity of the resulting hydrogels was evaluated. All hydrogel groups supported the attachment and growth of the MC3T3-E1 cells cultured on hydrogels. Additionally, adding AMBGs to the hydrogels increased osteoblastic differentiation of MC3T3-E1 cells. Incorporating ALN into HGB-0.5 % hydrogels also decreased the differentiation of RAW 264.7 cells into osteoclasts. These results highlight the potential of ALN-loaded HGB-0.5 % hydrogels with osteo-induction, osteo-conduction, and anti-osteoclastogenesis properties for treating osteoporotic fractures.