Capturing Magnesium Ions via Microfluidic Hydrogel Microspheres for Promoting Cancellous Bone 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.