Harnessing distinct bioactive profile of yak casein: A comparative study on hydrogels for infected wound healing.

Infected wounds impair tissue regeneration through persistent bacterial colonization, excessive oxidative stress, and prolonged inflammation. While casein-based hydrogels have emerged as promising wound dressings, investigations have predominantly focused on bovine milk casein (B-CA). Yak milk casein (Y-CA) differs markedly from B-CA in monomer composition, which will affect their bioactivity. In our study, composite hydrogels were fabricated using Y-CA or B-CA as the protein matrix, oxidized dextran (ODex) as a chemical crosslinker, and tannic acid (TA). This yields dual-crosslinked Y-CA@TA or B-CA@TA hydrogels. Systematic physicochemical characterization demonstrated that Y-CA-based hydrogels exhibited more uniform pore morphology, superior hydrophilicity, and enhanced mechanical strength compared to their B-CA counterparts. In vitro assays revealed that Y-CA@TA hydrogel exhibited significantly enhanced bioactivity compared to B-CA@TA hydrogel, including antibacterial and antioxidant abilities. For antibacterial activity, Y-CA@TA1.25 hydrogel exerted 74.0%, 97.4%, and 88.6% inhibition against E. coli, S. aureus, and MRSA, respectively, while B-CA@TA1.25 hydrogel only achieved 63.4%, 96.5%, and 82.0% antibacterial inhibition against the three strains, respectively. Moreover, antioxidant evaluation demonstrated a reactive oxygen species (ROS) scavenging efficiency of 99.7% for Y-CA@TA1.25 hydrogel, compared to 90.0% for B-CA@TA1.25 hydrogel. Importantly, our formulations are not toxic, and that Y-CA-based hydrogels enhanced L929 cell migration. In an MRSA-infected full-thickness murine wound model, Y-CA hydrogel achieved a high wound closure rate (98.3% for Y-CA@TA1.25 hydrogel in 12 days treatment). These findings establish Y-CA as a superior biopolymer matrix for multifunctional wound dressings, highlighting the therapeutic potential of alternative dairy-derived biomaterials in advanced wound care applications.