The fabrication of a highly efficient hydrogel based on a functionalized double network loaded with magnesium ion and BMP2 for bone defect synergistic treatment

Abstract Although the use of bioactive ions and proteins are crucial for bone defect repair, delivering them in a stable and controlled manner remains challenging. To achieve controlled delivery of osteogenic active factor, we developed a novel double network (DN) hydrogel capable of co-delivering Mg2+ ions and BMP2 in a controlled localized manner. This DN hydrogel was composed of poly (acrylamide) and chitosan, in which the poly (acrylamide) was cross-linked via covalent bond and the chitosan was grafted using bisphosphonate (BP) to form metal coordination bonds with Mg2+ ions. Due to this dynamic dissociation and re-association of the “BP-Mg2+” coordination bond, it was possible to deliver Mg2+ ions in a stable and controlled manner. Additionally, the obtained DN hydrogel exhibited an effective tensile strength (0.62 MPa), perfect stretchability (973% fracture strain), and good creep and recovery properties due to the dynamic cross-linking effect of “BP-Mg2+”. Additionally, the hydrogel could synergistically promote the proliferation and differentiation of mouse embryo osteoblast precursor cells (MC3T3-E1 cells) in vitro via the BMP2/Wnt pathway. In the skull defect rat model, this positive delivery government of Mg2+ ions and BMP2 synergistically accelerated bone regeneration. In conclusion, this dynamic cross-linked hydrogel containing Mg2+ ions established a new platform for the sustained release of osteogenesis factor and accelerated the bone regeneration process.