Nanocomplex-Integrated Multifunctional Hydrogel for Fast-Tracked Wound Repair Application: A Preclinical Evaluation

Deep or full-thickness injuries often exhibit impaired or delayed wound healing due to excessive reactive oxygen species (ROS), which impede tissue regeneration. To address this challenge, we have developed an injectable hydrogel based on gellan gum crosslinked with 1,4-phenylenediboronic acid (PBA) via boronate ester linkages, which also promote the incorporation of a cerium-rutin (Ce-R) nanocomplex. Cerium, known for its redox cycling properties, forms a stable nanocomplex with rutin, a plant-derived flavonoid through metal coordination, enhancing ROS-scavenging capacity, as validated by in vitro antioxidant assays. The Ce-R nanocomplex further interacts with PBA through reversible cis-diol boronate interactions, resulting in controlled and sustained release within the hydrogel network. Comprehensive physicochemical characterizations including FTIR, FE-SEM, and rheology confirmed successful crosslinking and structural stability of the hydrogel. The hydrogel exhibited excellent injectability and swelling capacity, absorbing up to 10 times its weight and facilitating the absorption of wound exudates while maintaining structural integrity. The hydrogel prevented the growth of both Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), signifying broad spectrum antimicrobial efficacy. In vivo studies using rat wound models demonstrated excellent hemocompatibility and significantly accelerated wound closure. These findings underscore the potential of Ce-R loaded boronate ester crosslinked gellan gum hydrogels as an effective therapeutic approach for deep wound healing.