Plant-Based Matrix for Bone Apatite Biomineralization: In Vitro Bioactivity, Biocompatibility, and Degradability of Lignin and Lignin-Silica Composites

Plant-derived biomaterials offer safer and ethically acceptable alternatives to animal-based implants for bone regeneration. Lignin, an abundant aromatic biopolymer, is attractive due to its durability and antioxidant and antibacterial properties; however, its structural heterogeneity remains a major limitation. Here, we investigate the bioactivity, degradability, and cytocompatibility of two structurally distinct lignins extracted from sorghum stems and their lignin–silica composites. Hydroxyapatite (HAP) mineralization was evaluated in simulated body fluid (SBF), and degradation was assessed in Tris-HCl buffer. Cytocompatibility and cell proliferation were tested using MC3T3-E1 pre-osteoblast cells. Lignin with a higher phenolic hydroxyl content promoted Ca²⁺-mediated HAP nucleation, showing mineralization after 14 days that further increased by 28 days. A∼17% lignin mass loss was measured after 21 days. Cell culture studies revealed enhanced proliferation when grown with 25–50 μg/mL lignin, whereas higher concentrations (>500 μg/mL) reduced cell viability, indicating a concentration-dependent response. Lignin–silica composites (75:25 wt %) exhibited higher mass loss (>20%) while maintaining good cytocompatibility even at elevated concentrations. These findings indicate that phenolic hydroxyl groups play a critical role in promoting mineralization and enabling controlled degradation. Importantly, lignin–silica composites combine bioactivity with favorable cytocompatibility, supporting their potential use as a bioactive matrix for bone regeneration.