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

Magnesium ions (Mg) play an essential role in the metabolism and regeneration of bone tissue. Appropriate amounts of Mg have been shown to promote osteogenic differentiation of bone-derived cells and angiogenesis of endothelial cells. However, the initial burst release of Mg may compromise the osteogenic effect, so the controlled release of Mg 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 Mg. For the initial release of Mg, polylactic acid (PLA) microspheres containing MgO and MgCO 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 Mg over a period exceeding 28 days. In vitro cell experiments, CS/PLA@MgO-MgCO 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.