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

Abstract

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.

Study on the Local Anti-Osteoporosis Effect of Polaprezinc-Loaded Antioxidant Electrospun Membrane

“…Osteoporotic bone defects suffer from poor bone quality, such as loose cancellous bone, thinning of cortical bone, and thinning of trabecular bone. 62 In addition, compared with normal bone tissue, osteoporotic bone tissue produces more ROS. 20 In our studies, what we loaded into the blend electrospinning membrane is famous for its ability to anti-oxidative stress.…”

Microcarriers in application for cartilage tissue engineering: Recent progress and challenges

“…Besides, methacrylic anhydride (MA) can be easily modified with gelatin to form photo-crosslinkable GelMA. Several studies have prepared GelMA MCs via ultraviolet cross-linking [ [179] , [180] , [181] , [182] , [183] ]. The gelatin MC has been endorsed for its potential in cartilage TE applications.…”

“…To the best of our knowledge, microcarriers with ferromagnetic domains or magnetization have been initially developed and explored for magnetic responsiveness and/or drug delivery and invasive surgery applications using magnetic guidance to target the lesion sites [ 180 , [326] , [327] , [328] ]. Targeted cell delivery is a promising technique to enhance the low targeting efficiency of cells via magnetization in the cartilage TE.…”

Biomaterials for microfluidic technology

“…Wongpinyochit et al [95] injected SF solution and organic solvent into two separate microfluidic channels, and then these two phases met and mixed at the junction, inducing the selfassembly of SF spheres. Microfluidic mixing was proved to not only allow the sphere size to be tuned by varying the flow Gelatin [116] Microsphere Physical crosslinking --Gelatin [117] Microsphere Enzymatic crosslinking --Gel-SH [119] Microsphere Chemical crosslinking BMSCs Cell BP-grafted GelMA [121] Microsphere Photo-crosslinking --…”

“…Due to the gelatin surface rich in moieties, GelMA microspheres can be loaded with drugs through both physical absorption and chemical grafting. In previous studies, we grafted bisphosphonates (BP) onto GelMA through the Schiff alkali reactivity and coordinate bond to construct functionalized microspheres that could capture magnesium ions, which shown the capability of stimulating cancellous bone regeneration (figure 5) [121]. We also produced lubricated microspheres through modifying GelMA microgels for OA treatment [122].…”