Polysaccharide architecture regulates the therapeutic performance of ferrous ion-coordinated hydrogels in frostbite...

In cold regions, frostbite wounds often involve severe vascular injury, tissue necrosis, and an increased risk of secondary infection, creating a need for multifunctional wound dressings. In this study, three Fe²⁺-coordinated polysaccharide hydrogels based on hyaluronic acid, sodium alginate, and xanthan gum were prepared under identical Fe²⁺ loading conditions to compare how representative polysaccharide architectures influence hydrogel microstructure, rheological behavior, Fe²⁺ release characteristics, and therapeutic performance in frostbite wound management. The results showed that Fe²⁺ could reversibly coordinate with carboxylate-containing polysaccharides and induce distinct architecture-dependent differences in network morphology and viscoelasticity. Functionally, all Fe²⁺-loaded hydrogels exhibited antibacterial activity, rapid hemostatic capability, and favorable biocompatibility. Additional antibacterial validation further showed that these hydrogels were effective against a clinical MRSA isolate. In mouse frostbite models, the hydrogels significantly accelerated wound closure, improved collagen deposition, and attenuated inflammatory responses. Quantitative histological analysis and Fe²⁺ release experiments further supported a structure-dependent divergence among the three systems, with the xanthan gum-based hydrogel showing the most favorable performance in MRSA-infected frostbite wounds. This advantage was likely associated with its elastic-dominant rheology, enhanced structural stability, and more sustained Fe²⁺ release behavior. Overall, this work provides a structure-guided comparative framework for understanding how representative polysaccharide architectures shape hydrogel behavior and therapeutic outcomes in frostbite wound management.