A thermosensitive chitosan hydrogel loaded with Thonningianin A nanoparticles promotes diabetic wound healing by modulating oxidative stress and angiogenesis.

Diabetic wounds are difficult to heal because of persistent oxidative stress and limited angiogenesis. However, traditional wound dressings cannot address these issues simultaneously. In this study, a thermosensitive chitosan (CS) hydrogel loaded with Thonningianin A (TA) nanoparticles (TA-NPs) was constructed. First, TA-NPs were developed via the nanoprecipitation technique. CS was subsequently combined with β‑sodium glycerophosphate (β-GP) to prepare a thermosensitive hydrogel matrix (CS/β-GP). Finally, composite hydrogels (TA-NPs@Gel) with antioxidant and angiogenesis-promoting properties were synthesized by incorporating TA-NPs into a CS/β-GP hydrogel matrix. Characterization revealed that the TA-NPs were uniformly spherical, with a particle size of 186.30 ± 1.15 nm and a zeta potential of -35.07 ± 0.61 mV. Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed the successful integration of TA-NPs into the hydrogel matrix. Both in vitro and in vivo studies demonstrated that TA-NPs@Gel exhibited potent antioxidant and angiogenic effects, significantly accelerating wound healing in a diabetic mouse model. Network pharmacology predictions indicated that TA-NPs@Gel promoted diabetic wound healing through the HIF-1 signaling pathway. Overall, the integration of TA-NPs into a hydrogel system has broad therapeutic potential for the treatment of diabetic wounds.