Organic–Inorganic Hybrid Scaffolds: Manganese-Doped Bioactive Glass Reinforced Carboxymethyl Chitosan–Alginate Composites for Pulp–Dentin Regeneration

The chemical design of organic/inorganic hybrids through sol–gel synthesis and polymer blending enables tailored properties for biomedical applications. Manganese-doped bioactive glass nanoparticles integrated into biopolymer networks provide tunable ion release and biomineralization capacity essential for hard tissue regeneration. Here, we synthesized and characterized different three-dimensional (3D)-printed carboxymethyl chitosan/alginate (CMC/Alg) scaffolds loaded with manganese-doped bioactive glass (Mn-BG) nanoparticles for pulp–dentin regeneration. 3D scaffolds were designed using Bioplotter software and printed with a 3D printer (Abtin, Iran) using homogeneous CMC/Alg mixtures. Mn-BG nanoparticles were synthesized via sol–gel. Nanoparticles and scaffolds were characterized with SEM, EDAX, FTIR, XRD, DLS, and zeta potential. The hemocompatibility, in vitro degradation, biomineralization, cytocompatibility, and stem cell differentiation were evaluated using Human Apical Papilla Stem Cells (SCAPs). Results confirmed successful synthesis of Mn-BG and Mn-BG/CMC/Alg scaffolds with dose-dependent bioactivity. The 1% Mn-BG scaffolds demonstrated optimal cell viability within 5 days, enhanced matrix mineralization over 14 days, and significantly upregulated osteogenic (ALP, BSP) and odontogenic (DSPP, DMP-1) markers (P < 0.05). Higher Mn concentrations (3–5%) exhibited cytotoxicity, while undoped scaffolds showed reduced bioactivity. The findings suggest that optimized 1% Mn-BG/CMC/Alg scaffolds offer a promising platform for pulp–dentin regeneration, bridging the gap between biomaterial design and clinical translation.