Fermentation-inspired macroporous and tough gelatin/sodium alginate hydrogel for accelerated infected wound healing

Gelatin and sodium alginate (SA) are two important biological macromolecules, exhibiting excellent biocompatibility and gel-forming ability. However, traditional SA and gelatin hydrogel displays limited mass transport, low porosity, instability, and poor mechanical properties extremely restricted their therapeutic effect and application scenarios. Herein, microbial fermentation and synergistic toughening strategies were used for preparing macroporous and tough hydrogel. The study investigated the fermentation and toughening conditions of hydrogel. The hydrogel composed of CaCl₂ cross-linked physically network and EDC/NHS cross-linked covalently network, exhibiting significantly improved mechanical properties, and excellent recovery efficiency. In addition, the hydrogel has a hierarchical macroporous structure of 100-500 μm, demonstrating high porosity of 10 times, swelling rate of 1541.0 %, and high mass infiltration capability. Further, after Ag⁺ treatment, the macroporous hydrogel dressing showed outstanding biocompatibility. Compared with non-porous hydrogel, the resulting macroporous hydrogel dressing displayed high antibacterial and antioxidant properties. It could effectively alleviate intracellular ROS formation induced by H₂O_2.In vivo experiments indicated that it has significantly better effect than non-porous hydrogel in accelerating wound healing. The overall results suggest that the gelatin/SA-based macroporous and tough hydrogel proposed in this study holds excellent prospects for application in wound dressings.