Mg2+ loaded heparin functionalized injectable gelatin hydrogel promotes bone defect repair

Hydrogels have emerged as promising materials for bone tissue engineering applications. However, a significant challenge in osteogenic hydrogels lies in insufficient osteogenic activity, limiting efficacy in bone defect repair. During hydrogel construction, the selection of appropriate cross-linking molecules to impart enhanced biological properties remains a critical factor for effective bone defect repair. Herein, a hydrogel constructed using methacrylated gelatin, methacrylated heparin, alendronic acid, and Mg 2+ was used to promote the repair of bone defects. HepMA was successfully prepared by the methacrylic anhydride. The carboxyl groups of HepMA were modified to synthesize HepMA-BP. The incorporation of HepMA-BP reduced the injection resistance of GelMA, and upon photo-crosslinking, the hydrogel demonstrated the capacity for Mg 2+ loading and sustained release of phosphorus (P) and magnesium (Mg). In addition, heparin functionalized hydrogels significantly promoted angiogenesis, inhibited osteoclastic differentiation, and enhanced osteogenic differentiation of BMSCs after binding Mg 2+ . At 8 weeks, the Mg 2+ loaded hydrogel could significantly repair bone defects in rats. GelMA-BP-Mg hydrogel enhances osteogenesis by promoting Vascular Cell Adhesion Molecule 1(VCAM1) overexpression via the TNF-α pathway, representing a potential underlying mechanism. Therefore, Mg 2+ loaded heparin functionalized hydrogel, with high osteogenic activity, may offer a reliable solution for bone defect repair in the near future.