Quaternary Ammonium Chitosan Hydrogel Platform with Zinc-Enhanced Bioactivity toward Scar-Free Wound Healing

Scar-free wound regeneration remains a challenge, as it requires controlled collagen and extracellular matrix deposition to prevent excessive fibrosis. To overcome this issue, wound dressings that incorporate hydrogels and possess superior biochemical and mechanical properties integrated with bioactive compounds have been explored. In this paper, the composite hydrogel has been developed using O-chitosan quaternary ammonium salt (O-HACC) and 3-maleimidopropionic acid-modified pullulan polysaccharide (PL-MA), with incorporated polydopamine-loaded asiaticoside Zif-8 nanoparticles. The hydrogel demonstrated efficient antibacterial activity, with inhibition rates of 76.6 ± 1.6% against Staphylococcus aureus and 69.9 ± 7.3% against Escherichia coli, favourable self-healing (within 1 min), and adhesive properties on various substrates, including skin, glass, plastic, and metal. The in vivo experiments showed accelerated healing, with the wound area reduced to 2.33 ± 0.18 mm 2 by day 12 in the AA@HP11-treated group compared with 16.89 ± 0.57 mm 2 in the control group ( p < 0.001). The in vivo experiments also demonstrated the reduced expression of α-SMA and TGF-β1, indicating limited fibrosis. Additionally, HE and Masson stainings indicated that zinc particle-embedded hydrogel enhanced wound repair, with increased collagen deposition by day 6, followed by a subsequent decrease by day 12, suggesting a lower risk of scar formation. These findings suggest that the fabricated hydrogel may contribute to improved wound healing outcomes and reduced fibrosis, highlighting its potential for future scar reduction therapies.