Precisely Controlled Delivery of Magnesium Ions Thru Sponge-like Monodisperse PLGA/nano-MgO-alginate Core-shell Microsphere Device to Enable In-situ Bone Regeneration

A range of magnesium ions (Mg) used has demonstrated osteogenic tendency in vitro. Hence, we propose to actualize this concept by designing a new system to precisely control the Mg delivery at a particular concentration in vivo in order to effectively stimulate in-situ bone regeneration. To achieve this objective, a monodisperse core-shell microsphere delivery system comprising of poly (lactic-co-glycolic acid) (PLGA) biopolymer, alginate hydrogel, and magnesium oxide nano-particles has been designed by using customized microfluidic capillary device. The PLGA-MgO sponge-like spherical core works as a reservoir of Mg while the alginate shell serves as physical barrier to control the outflow of Mg at ∼50 ppm accurately for 2 weeks via its adjustable surface micro-porous network. With the aid of controlled release of Mg, the new core-shell microsphere system can effectively enhance osteoblastic activity in vitro and stimulate in-situ bone regeneration in vivo in terms of total bone volume, bone mineral density (BMD), and trabecular thickness after operation. Interestingly, the Young's moduli of formed bone on the core-shell microsphere group have been restored to ∼96% of that of the surrounding matured bone. These findings indicate that the concept of precisely controlled release of Mg may potentially apply for in-situ bone regeneration clinically.