Fabrication of Lithium/Strontium‐Releasing Smart Bioactive Glasses with Anti‐Inflammatory and Osteogenic Effects Tailored to Pathological Stages

Bioactive glasses (BGs) are highly biocompatible with affinity for hard tissues and exhibit high bioactivity through ion release. Smart BGs that allow controlled ion release are required because uncontrolled release can lead to unexpected adverse effects on tissue regeneration. Strontium promotes osteoblast differentiation of mesenchymal stem cells (MSCs) and inhibits osteoclast activity. In this study, the release profile of strontium is regulated by the incorporation of aluminum into a phosphate-based BG. Furthermore, composites of strontium-releasing BG and lithium-releasing BG (Li/Sr-BG) show stepwise ion release, with rapid lithium release followed by sustained strontium release. Li/Sr-BG increases the expression of osteogenic markers and mineral deposition in MSCs, but suppresses osteoclast maturation, including multinucleation and osteoclast marker expression. Additionally, application of Li/Sr-BG to inflammatory macrophages decreases phagocytic activity and inflammatory gene expression, while increasing the expression of anti-inflammatory markers. Analysis of signaling proteins reveals that osteogenic and anti-inflammatory effects of Li/Sr-BG are attributed to the release of strontium and lithium, respectively. This study demonstrates that Li/Sr-BGs can be used for the development of novel smart bioactive materials that effectively suppress inflammation and promote bone formation in a manner that follows the process of bone regeneration.