Controlled release of magnesium ions from PLA microsphere-chitosan hydrogel complex for enhancing osteogenic and...

Magnesium ions (Mg²⁺) play an essential role in the metabolism and regeneration of bone tissue. Appropriate amounts of Mg²⁺ have been shown to promote osteogenic differentiation of bone-derived cells and angiogenesis of endothelial cells. However, the initial burst release of Mg²⁺ may compromise the osteogenic effect, so the controlled release of Mg²⁺ is the critical consideration of the magnesium-containing tissue-engineered bone materials. This study proposes a microsphere-hydrogel complex to enhance the sustained-release effect and prolong the release cycle of Mg²⁺. For the initial release of Mg²⁺, polylactic acid (PLA) microspheres containing MgO and MgCO₃ were fabricated with uniform morphology. Further microspheres were incorporated into the chitosan-based hydrogel to form microsphere- hydrogel complex for extended release. The complex demonstrated effective sustained release of Mg²⁺ over a period exceeding 28 days. In vitro cell experiments, CS/PLA@MgO-MgCO₃ significantly enhanced migration and osteogenic differentiation of MC3T3-E1. Meanwhile, it can facilitate the generation of blood vessels in HUVECs. In conclusion, the magnesium-loaded microsphere-hydrogel complex achieves excellent dual sustained-release properties with an extended-release cycle while enhancing vascularized osteogenic activity in vitro, showing promising prospects for clinical application in bone defect treatment.