Three-dimensionally printed mesoporous bioactive glass for craniomaxillofacial bone regeneration: Material evolution, functional mechanisms, and clinical translation

Craniomaxillofacial (CMF) bone defects pose significant regenerative challenges due to complex anatomy and physiological demands. While autologous bone grafting remains the gold standard, it is limited by donor-site morbidity and supply constraints. Mesoporous bioactive glass (MBG), characterized by its ordered nanoporous structure and superior bioactivity, offers a promising alternative. This review systematically analyzes the integration of MBG with 3D printing technologies, including direct ink writing, stereolithography, selective laser sintering, and fused deposition modeling. We critically evaluate physicochemical challenges such as rheological optimization and thermal devitrification while elucidating the “osteo-immune-vascular” axis orchestrated by these scaffolds. Specifically, we discuss how ionic dissolution products modulate macrophage polarization, stabilize hypoxia-inducible factor-1α (HIF-1α) to induce CD31ʰⁱEmcnʰⁱ vessel formation, and activate Wnt/β-catenin signaling. Despite promising preclinical data, clinical translation faces hurdles regarding regulatory approval and manufacturing standardization. Future developments in 4D printing, AI-driven inverse topology design, and organ-on-a-chip validation represent a paradigm shift from passive substitution to active regeneration, paving the way for the tissue-engineered reconstruction of complex CMF defects.