Dual-thermo-responsive microneedle patch for accelerated diabetic wound healing through on-demand drug release and active temperature management

Diabetic foot ulcers (DFUs), prone to infection and deterioration without timely intervention, significantly increase risks of amputation and mortality. Elevated local temperature in DFUs further impedes the healing process. Although microneedles (MNs) represent a promising strategy for DFUs treatment, conventional passive drug release systems suffer from slow release kinetics and low utilization efficiency. To address these limitations, we developed a dual-thermo-responsive microneedle patch (DTMN) that actively controls drug delivery through temperature-induced structural transitions. The inner layer consists of sodium alginate-poly (N-isopropylacrylamide) (SA-PNIPAM) loaded with sucrose octasulfate sodium salt (SOS), utilizing the volume phase transition of PNIPAM to accelerate drug expulsion in response to temperature change. The outer layer comprises a polyethylene glycol/polylactic acid-glycolic acid copolymer (PEG-PLGA) loaded with urea, which undergoes gel-sol transition to facilitate controlled urea release and wound cooling. An upper electrospun nanofiber membrane made of poly (ε-caprolactone)/chitosan (PCL/CS) incorporated with tetracycline hydrochloride (TH) and SOS provides enhanced antibacterial efficacy and increased drug loading capacity. The resulting DTMN exhibits efficient drug release (85.23% SOS and 35.44% urea-derived ammonia at 24 h), remarkable antioxidant activities, potent antibacterial performance, excellent biocompatibility, and significantly enhanced wound healing. This multifunctional system offers a novel and effective strategy for the management of DFUs.