Mg 2+ (Magnesium ion) can affect bone tissue metabolism by regulating related signaling pathways in bone metabolism. However, how to realize precise controlled release of Mg 2+ in bone regeneration treatment still presents a challenge. Herein, for the first time, the GelMA-BP (Gelatin Methacryloyl-Bisphosphonate) and the composite nano-bubble system are fused to construct the Mg 2+ blasting controlled-release hydrogel microspheres, the stability of the nano-bubbles in the microspheres is enhanced through metal coordination complexation, and the burst of the nano-bubbles is controlled by using ultrasonic cavitation to achieve the precise controlled release of Mg 2+ , ultimately effectively promoting bone reconstruction. First, GelMA-BP composite is prepared by Schiff base reaction. Second, the nanobubble BP (Bisphosphonate) system is constructed, and Mg 2+ is combined with the ligand coordination to prepare the composite nanobubble system. Thirdly, through Mg 2+ co-coordination, the ultrasound-triggered Mg 2+ blasting controlled release microspheres were prepared to achieve bone repair. Overall, this innovative strategy effectively solves the problem of accurate controlled release of Mg 2+ , and finally effectively activates in situ bone tissue regeneration.
Metal ions are important trace elements in the human body, which directly affect the human metabolism and the regeneration of damaged tissues. For instance, the advanced combination of magnesium ions (Mg2+) and bone repair materials make the composite materials have the function of promoting vascular repair and enhancing the adhesion of osteoblasts. Herein, inspired by magnets to attract metals, we utilized the coordination reaction of metal ion ligand to construct a bisphosphonate-functionalized injectable hydrogel microsphere (GelMA-BP-Mg) which could promote cancellous bone reconstruction of osteoporotic bone defect via capturing Mg2+. By grafting bisphosphonate (BP) on GelMA microspheres, GelMA-BP microspheres could produce powerful Mg2+ capture ability and sustained release performance through coordination reaction, while sustained release BP has bone-targeting properties. In the injectable GelMA-BP-Mg microsphere system, the atomic percentage of captured Mg2+ was 0.6%, and the captured Mg2+ could be effectively released for 18 days. These proved that the composite microspheres could effectively capture Mg2+ and provided the basis for the composite microspheres to activate osteoblasts and endothelial cells and inhibit osteoclasts. Both in vivo and in vitro experimental results revealed that the magnet-inspired Mg2+-capturing composite microspheres are beneficial to osteogenesis and angiogenesis by stimulating osteoblasts and endothelial cells while restraining osteoclasts, and ultimately effectively promote cancellous bone regeneration. This study could provide some meaningful conceptions for the treatment of osteoporotic bone defects on the basis of metal ions.
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