Magnesium-Based Composite Calcium Phosphate Cement Promotes Osteogenesis and Angiogenesis for Minipig Vertebral Defect Regeneration

Abstract

Calcium phosphate cement (CPC) is an injectable bone cement with excellent biocompatibility, widely used for filling bone defects of various shapes. However, its slow degradation, insufficient mechanical strength, and poor osteoinductivity limit its further clinical applications. In this study, we developed a novel composite magnesium-based calcium phosphate cement by integrating magnesium microspheres into PLGA fibers obtained through wet spinning and incorporating these fibers into CPC. The inclusion of magnesium-based PLGA fibers enhanced the compressive strength and degradation rate of CPC, with the degradation rate of the magnesium microspheres being controllable to allow for the sustained release of magnesium ions. In vitro experiments showed that magnesium-based CPC enhanced the proliferation and migration of MC3T3-E1 and HUVECs. Additionally, the magnesium-based composite CPC not only enhanced osteogenic differentiation of MC3T3-E1 cells but also promoted angiogenesis in HUVECs. In vivo experiments using a vertebral bone defect model in Bama miniature pigs showed that the magnesium-based composite CPC significantly increased new bone formation. Additionally, compared to the CPC group, this composite exhibited significantly higher levels of osteogenic and angiogenic markers, with no inflammation or necrosis observed in the heart, liver, or kidneys, indicating good biocompatibility. These results suggest that magnesium-based composite CPC, with its superior compressive strength, biodegradability, and ability to promote vascularized bone regeneration, holds promise as a minimally invasive injectable material for bone regeneration.