Thermoresponsive hydrogel dressings for precision drug release under physiological conditions

Thermally responsive hydrogel-based drug delivery systems encounter significant challenges, such as imprecise thermal response thresholds and incomplete drug release. In this study, maleic anhydride-modified cyclodextrin (MA-β-CD) is incorporated into poly (N-isopropyl acrylamide) (PNIPAM) hydrogel via covalent bonding for the purpose of gallic acid delivery. The introduced isopropyl group forms a host–guest interaction with the hydrophobic cavity, effectively modulating both the phase transition temperature and the contraction rate of PNIPAM. Due to the host–guest interactions, the phase transition temperature of conventional PNIPAM hydrogel (32 °C) is adjusted to fall within the physiological temperature range (36 °C-38 °C) relevant to human wounds for precise regulation of drug release. Moreover, when the hydrogel attains its phase transition temperature of 37 °C, it demonstrates a volume shrinkage rate of 55.6 % and a drug release efficiency of 95.34 %. Compared with the hydrogel without MA-β-CD (with a shrinkage rate of 5.3 % and a drug release rate of 35.31 %), the modified PNIPAM hydrogel exhibits a 10.5-fold increase in shrinkage and a 2.7-fold enhancement in drug release. Notably, the hydrogel dressing possesses remarkable antimicrobial efficacy and excellent biocompatibility. In a mouse model, it significantly accelerates wound closure and promotes the regeneration of a fully stratified epidermis. This work is of guiding significance for the preparation of high-performance thermo-responsive hydrogel dressings.