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 (Mg 2+ ) 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 Mg 2+ . By grafting bisphosphonate (BP) on GelMA microspheres, GelMA-BP microspheres could produce powerful Mg 2+ capture ability and sustained release performance through coordination reaction, while sustained release BP has bonetargeting properties. In the injectable GelMA-BP-Mg microsphere system, the atomic percentage of captured Mg 2+ was 0.6%, and the captured Mg 2+ could be effectively released for 18 days. These proved that the composite microspheres could effectively capture Mg 2+ 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 Mg 2+ -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.

Microfluidic hydrogel microspheres have been broadly studied across a wide range of industries and applications, and their use in the medical field, including control cells and drug delivery, is increasing. The usual design of these materials is intended to enable the efficient and smart encapsulation of cells and/or drugs in microspheres in which the functionalities and features are effectively controlled, lending itself some unique properties. These characteristics promote exchanges and cooperation in multiple disciplines and boost the development of precision medicine, new manufacturing technologies, and applied materials. This review begins with a discussion of microfluidic hydrogel microspheres and then introduces the preparation equipment, main principles, and related characteristics of the microspheres. Furthermore, the medical applications of microfluidic hydrogel microspheres for delivering cells and drugs are emphasized. Finally, this review discusses perspectives and future directions for accelerating the development and application of microfluidic hydrogel microspheres for controlled delivery.