Abstract
Osteoporosis, a prevalent metabolic bone disease, poses a significant challenge for bone repair in aged populations. Soy-derived osteogenic peptide (SOP) holds promise but its clinical translation is hampered by rapid enzymatic degradation and poor oral bioavailability, representing a major challenge that necessitates the development of a protective delivery system. To address this, we developed a novel composite hydrogel based on fish gelatin and sodium alginate (SA/FG) as an oral delivery vehicle to overcome these limitations. Systematic characterization revealed that the SA/FG formulation offers distinct advantages: the incorporation of an optimal amount of SA significantly enhanced the mechanical strength and stability of the hydrogel, addressing the common weakness of single-network gelatin hydrogels, while maintaining a high water content (~90%) and a superior rehydration capacity (83.65% in distilled water). In a glucocorticoid-induced zebrafish osteoporosis model, the SOP-loaded SA/FG hydrogel significantly increased skull bone mass by 120.17% and improved larval swimming behavior, markedly outperforming the free SOP group. This study presents the first report of an SA/FG composite hydrogel for effective oral delivery of an osteogenic peptide. The system demonstrates great potential as a functional food or supplement for preventing and treating osteoporosis, offering an innovative strategy to enhance peptide stability and bioavailability through a biocompatible, double-network carrier.