Photocrosslinkable and ultrasound-responsive composite hydrogels for osteoporotic bone defect repair

Osteoporotic bone defects pose a threat to the lives of senior citizens, leading to prolonged hospitalization and increased cardiovascular risks due to imbalances in the bone tissue microenvironment. This study established a multifunctional composite system integrating ultrasound-responsive microsphere carriers and photocrosslinkable hydrogel substrates. The microsphere with PVP/ALG (1 : 1) group exhibited ultrasound‑responsive behavior; such feature was not detected for PVP/ALG = 3 : 1 and PVP/ALG = 1 : 3. Systematic investigations regarding the influence of coagulation bath variation on the cross-linking behavior and resultant properties of sodium alginate remain scarce. In this work, we fabricated risedronate (Ris)-loaded ultrasound-responsive microspheres (MS) and incorporated these microspheres into a photopolymerized vancomycin (Van)-loaded GelMA hydrogel system for the repair of osteoporotic bone defects. This work firstly explored the formation and characterization of ALG/PVP composite microspheres prepared in anhydrous ethanol medium. While the cross-linking bath is converted from an absolute ethanol-calcium solution to an aqueous calcium ion solution, sodium alginate microspheres prepared by electrostatic spraying exhibit optically visible responsive performance, presenting a frog-egg-like morphology, and possess ultrasound responsive characteristics. The GelMA@Van/MS@Ris hydrogel exhibits a loose and porous structure, with a 14-day degradation rate of 41.94%, enabling effective sustained release of the loaded vancomycin and risedronate. The GelMA@Van/MS@Ris hydrogel exhibits excellent biocompatibility and osteogenesis, which enhances alkaline phosphatase expression and promotes calcium deposition. In RT-PCR experiments, the GelMA@Van/MS@Ris group showed 1.61-, 1.40-, 2.45-, and 2.38-fold up-regulations in the gene expression levels of Col 1, Alp, Ocn, and Runx2 compared to the GelMA/MS group. In in vivo experiments, GelMA@Van/MS@Ris effectively promotes bone tissue regeneration under osteoporotic pathological conditions. The bone index of GelMA@Van/MS@Ris is 1.73 times that of GelMA/MS. Collectively, this work provides a feasible strategy for constructing bioactive scaffold materials with integrated antibacterial, controlled-release, and osteogenic functions, offering new insights for the development of biomaterials in bone tissue engineering.