Investigation of the biocompatibility and osteogenic effects of magnesium-doped chloride-containing bioactive glasses

Abstract

Bioactive glass (BG) degrades in vivo, releasing therapeutic ions and forming an apatite-like phase to repair hard tissues. While many BG-derived materials have been employed clinically, researchers continue to work on improving the physicochemical properties and biological functions of BG due to its inappropriate degradation rate and unsatisfactory bone repair effects. Our previous work revealed that the incorporation of chlorine (Cl) into BG expanded the glass structure, facilitating glass degradation and rapid hydroxyapatite formation. Chloride-containing bioactive glasses (GPCl) showed good osteogenesis effects in vitro and in vivo. However, the fast degradation rate of GPCl may cause a mismatch between bone formation and glass degradation, limiting its bone repair efficacy. This study incorporated various amounts of magnesium (Mg, 0-20 mol%) into GPCl to regulate its degradation behavior and enhance its bone regeneration ability. Four glasses were synthesized using a melt-quench method. The in vitro glass bioactivity was evaluated in Minimum Essential Medium-α (α-MEM), while the in vivo osteogenic effect of Mg-doped chloride-containing bioactive glasses (GPMgCl) was investigated on a rat skull critical-size defect and compared with the commercially available bone substitute (Bio-Oss^®). Additionally, the blood and main organs of rats were collected to assess the biocompatibility of GPMgCl. Our results demonstrated that Mg delayed the degradation rate of GPCl and the rate of hydroxyapatite formation while maintaining excellent bioactivity in α-MEM. GPMgCl promoted the expression of osteogenic genes osteocalcin (OCN), bone morphogenetic protein 2 (BMP2), and vascular endothelial growth factor (VEGF), and facilitated the formation of the mineralized nodules. Moreover, it exhibited superior osteogenic effects compared to Bio-Oss^® in vivo, with GPMg10Cl showing optimal bone regeneration ability. Blood biochemical analyses, blood cell tests, and hematoxylin-eosin staining of organs confirmed the excellent biocompatibility of GPMgCl. Incorporating Mg into GPCl is a promising approach to regulate degradation behavior and enhance osteogenic performance, making GPMgCl a promising bone substitute material to meet future bone repair needs.

Keywords

Bioactive glass / chloride / magnesium / bone regeneration / biocompatibility

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