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Research Article: A double-network fish gelatin/sodium alginate composite hydrogel as a carrier for the sustained release of a soy-derived osteogenic peptide

Date Published: 2025-12-15

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.

Introduction:
Osteoporosis and related bone injuries have emerged as a critical global public health challenge, with their prevalence and impact exacerbated by rapidly aging populations ( 1–3 ). This systemic skeletal disorder is characterized by reduced bone mass, microarchitectural deterioration of bone tissue, and an increased risk of fragility fractures, primarily resulting from an imbalance between osteoclastic bone resorption and osteoblastic bone formation ( 4 , 5 ). The treatment and repair of osteoporotic bone defects…

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