In situ antibacterial thermosensitive hydrogel as a versatile platform for diabetic wound therapy and molecular monitoring

Chronic diabetic wounds are difficult to manage because of persistent inflammation, impaired tissue regeneration, and high infection risk under hyperglycemic conditions. Microbial colonization further aggravates inflammatory responses and disrupts the normal progression of wound healing. Here, we developed a multifunctional hydrogel composed of Pluronic F-127 (PF) and tannic acid (TA), where TA acted as a natural crosslinker to improve network stability and gelation behavior. The PF/TA hydrogel exhibited in situ thermosensitive gelation within the physiological temperature range (33-37 °C), enabling rapid solidification and strong adhesion to wound surfaces. Rheological and microscopic analyses confirmed favorable viscoelasticity and a microporous structure. The hydrogel also showed antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus. To provide therapeutic functionality, the hydrogel was loaded with Humulus scandens (HS) or Vitis vinifera (VV) extracts. These extracts reduced Pecam1 expression, promoted fibroblast proliferation, increased Col1a1 expression, and induced M2 macrophage polarization in vitro. For wound monitoring, gold nanoparticle-based mRNA nanosensors (NanoFlares) were incorporated to detect Pecam1 and Col1a1 mRNA associated with inflammatory and proliferative healing phases. In non-infected murine wound models, HS- and VV-loaded PF/TA hydrogels significantly accelerated wound closure under both nondiabetic and diabetic conditions, demonstrating promising potential for diabetic wound therapy and monitoring applications.