Controlled and Sequential Delivery of Stromal Derived Factor-1 alpha (SDF-1 alpha) and Magnesium Ions from Bifunctional Hydrogel for Bone Regeneration

Bone healing is a complex process that requires the participation of cells and bioactive factors. Stromal derived factor-1 alpha (SDF-1 alpha) and magnesium ions (Mg2+) both are significant bioactive factors for cell recruitment and osteogenesis during bone regeneration. Thus, a bifunctional hydrogel containing a sequential delivery system is fabricated to improve osteogenesis. During sequential delivery of the hydrogel, SDF-1 alpha is predominantly released at the early stage of bone mesenchymal stem cells (BMSCs) recruitment, while Mg2+ are constantly delivered at a later stage to improve osteogenic differentiation of recruited cells. In addition, due to the early release of SDF-1 alpha, the hydrogel showed strong BMSCs recruitment and proliferation activity. Mg2+ can not only induce up-regulation of osteogenic gene expression in vitro, but also promote bone tissue and angiogenesis in vivo. Taken together, the injection of xanthan gum-polydopamine crosslinked hydrogel co-loading SDF-1 alpha and Mg2+ (XPMS hydrogel) provides a novel strategy to repair bone defects.