Kaempferol-ZIF-8 Hybrid System Augments Bioadhesive Thermoresponsive Hydrogel for Enhanced Diabetic Wound Healing

Diabetic wound dressings require strong adhesion, painless removal and effective treatment against chronic inflammation. Herein, a multifunctional hydrogel KAE@ZIF-8/Mg²⁺/PDA-NIPAM-PAM (abbreviated as KAE@ZIF-8/Mg²⁺/PNP) was prepared by copolymerizing dopamine, N-isopropylacrylamide, and acrylamide with kaempferol-loaded ZIF-8 nanoparticles. The hydrogel integrates thermosensitive gelation and bioadhesion delivery to treat diabetic wounds. It forms gel within 1 min at 37°C with reliable tissue adhesion, while adhesion drops sharply after 20 min immersion at 10°C for trauma-free detachment. This hydrogel achieves pH-responsive drug release, with 24 h cumulative KAE release rates of 49.8 ± 1.33% at pH 5.3 and 18.1 ± 0.82% at pH 7.4. It possesses excellent hemostatic, pro-angiogenic, anti-inflammatory, and antioxidant properties. Moreover, the hydrogel exhibits a compressive modulus of 89.98 kPa and favorable cytocompatibility, maintaining over 90% viability of NIH/3T3 fibroblasts.