Bilayer Microneedle Patch Loaded with Keratin-Based Hydrogen Sulfide Donor and Ciprofloxacin for Diabetic Wound Healing

Persistent overoxidation, inflammation, and bacterial infection impede diabetic wound healing. As the third biological gasotransmitter, hydrogen sulfide (H 2 S) can modulate inflammation, mitigate oxidative stress, and facilitate angiogenesis, potentially promoting diabetic wound healing. In this study, bilayer microneedle patches (MNs) were prepared through a two-step mold-casting process using blends of poly(vinyl alcohol) and poly(vinylpyrrolidone) as substrates. The tip layer was loaded with a keratin-based hydrogen sulfide donor (KAT) and ciprofloxacin hydrochloride (CIP), while the backing layer was integrated with glutathione and CIP. The patches exhibited a well-arranged microarray and enough mechanical properties to penetrate the skin. The patches demonstrated the self-catalytic generation of H 2 S and the delivery of CIP. Additionally, the patches exhibited excellent antioxidant and antibacterial properties. More importantly, MNs can polarize macrophages to anti-inflammatory phenotypes (M2), enhance the proliferation and migration of L929 cells, and promote HUVEC angiogenesis. The wound healing in diabetic rat models confirmed that the MN patches reduced the inflammatory response, accelerated collagen deposition, and promoted neovascularization, thereby accelerating diabetic wound healing. Overall, the bilayer patches demonstrated outstanding potential for wound dressing applications.