A Scallop Active Peptide-Incorporated Carboxymethyl Chitosan/Oxidized Sodium Alginate Hydrogel for Accelerating Skin Wound Healing and Tissue Regeneration

In this study, a novel composite hydrogel was developed based on oxidized sodium alginate (OSA), synthesized via sodium periodate oxidation, and incorporated into a carboxymethyl chitosan (CMCS) matrix. Scallop active peptides (SAPs), a marine-derived bioactive component with outstanding antioxidant and pro-regenerative activities, was introduced to endow the hydrogel with enhanced biological functions, which is of great significance for breaking the functional limitations of traditional single-component hydrogels. The construction of a dynamic covalent network, driven by the Schiff base reaction, was confirmed through structural characterization using FT-IR and1H-NMR. The hydrogel exhibited favorable physicochemical properties, including shear-thinning behavior, significant self-healing capability, and a uniform porous microstructure that effectively mimics the extracellular matrix (ECM). In vitro evaluations revealed excellent biocompatibility and potent pro-angiogenic potential, as evidenced by enhanced HUVEC migration and tube formation. In a rat model of full-thickness skin wounds, the CMCS/OSA/SAPs hydrogel significantly accelerated wound closure and promoted re-epithelialization and organized collagen deposition. Furthermore, immunohistochemical analysis confirmed upregulated VEGF and α-SMA expression, alongside reduced inflammatory levels (decreased iNOS), indicating potent tissue-regenerative and immunomodulatory functions. Overall, this work presents a multifunctional hydrogel system that integrates antioxidant, anti-inflammatory, and tissue-regenerative properties, offering a promising strategy for deep-wound healing. This study highlights the significant potential of marine-derived bioactive proteins/peptides in the development of advanced biomedical materials.