<i>In vitro</i> assessment of injectable alginate-based scaffolds functionalized with osteotropic drug-loaded bioactive glass

Osteoporotic bone presents a compromised regenerative niche, with reduced osteoblast function and an imbalance between bone formation and resorption, limiting the success of conventional defect filling strategies. Injectable biomaterials that conform to irregular defects and provide localized osteogenic cues are particularly relevant. Here, we developed injectable sodium alginate hydrogels (HPs) incorporating 45S5 bioactive glass (HB) or the same glass functionalized with two osteoporosis-relevant osteotropic drugs deliberately selected for distinct mechanisms of action: raloxifene hydrochloride (HBRx; selective estrogen receptor modulation) and strontium ranelate (HBSr; dual action on bone remodeling). Within the scope of this work, we established material feasibility and comparative<i>in vitro</i>performance through quantitative assessment of microstructure and surface behavior, together with cytocompatibility and osteogenic readouts. Glass incorporation remodeled the scaffold microstructure, increasing mean pore size from 54.0 ± 17.9 µm (HP) to 139.9 ± 51.5 µm (HB), while drug functionalization produced intermediate pores (84.8 ± 26.3 µm for HBRx; 85.5 ± 37.4 µm for HBSr). The increased inorganic contribution in the composites was reflected by higher residual mass at 800 °C (from 33.5% in HP to 45.0%-48.3% in glass-containing groups) and by shifts in wettability, with all formulations remaining hydrophilic (<i>θ</i>< 90°) but differing between functionalizations (44.2 ± 9.1° for HBRx vs 62.4 ± 11.8° for HBSr). All HPs were cytocompatible (day 7 relative viability ⩾70%) and supported osteogenic readouts (protein production, alkaline phosphatase activity, calcium deposition, and mineralized nodules), with HBSr showing the most favorable overall cellular response among the composites. Collectively, these findings indicate that osteoporosis-relevant drug-functionalized 45S5 within injectable alginate HPs provides a quantitative route to tune microstructure and interfacial behavior while preserving cytocompatibility and osteogenic potential. Future work will prioritize<i>in vivo</i>validation in osteoporotic models to assess bone repair efficacy and determine whether localized delivery mitigates drug-specific drawbacks associated with systemic therapies.