Moist heat sterilization-resistant hyaluronic acid hydrogels co-crosslinked by ternary metal ions for full-cycle wound care.

Hyaluronic acid (HA) hydrogels generally exhibit poor resistance to moist heat sterilization. Modification with a single metal element (ME) fails to synergistically optimize multiple functional properties. The destructive impact of terminal sterilization on hydrogel network integrity has often been overlooked in the biomedical hydrogel field, which may hinder clinical translation. To address these challenges, this study developed a ternary ME co-crosslinked HA hydrogel incorporating Mg2 +/Zn2+/Fe3+. The formulation was optimized using Box-Behnken response surface methodology. Moist heat sterilization at 121℃ for 12 min, corresponding to a sterility assurance level (SAL) ≤ 10-6, was incorporated into the formulation optimization and performance evaluation process. Rheological measurements confirmed that the ME-crosslinked hydrogels retained suitable mechanical properties for wound dressing application after sterilization. In vivo experiments demonstrated that the M-ME@Gel achieved rapid hemostasis, with a hemostatic time of 28.0 ± 5.86 s and blood loss of 57.93 ± 11.71 mg. It also accelerated wound closure, resulting in near-complete healing in mice by day 11 and a wound-closure rate of 97.72 ± 1.93% in rabbits by day 14. This study provides a strategy for enhancing the moist heat sterilization resistance of biomedical hydrogels, and offers a reference for the translational development of wound dressing.