Development of Antiseptic and Epidermal Growth Factor Co-Loaded Thermoresponsive Composite Hydrogel for Wound Healing: Fabrication, Characterization, and In Vitro Functional Assessment

Deep wounds often lead to severe complications such as persistent infection, biofilm formation, and high patient morbidity. While skin injuries can usually be managed with functional dressings, wounds in deep layers without sufficient treatment may serve as primary entry points for bacterial infection, thereby posing a significant life-threatening risk to patients. With the rising prevalence of chronic diseases and an aging population, effective strategies for enhanced wound healing are still in high demand. In this study, an injectable and thermoresponsive hexamethylene diisocyanate-Pluronic F127 copolymer-hyaluronic acid composite hydrogel loaded with polyhexamethylene biguanide (PHMB) and epidermal growth factor (EGF), named PEHHPG, was developed for joint therapy of deep wounds. PEHHPG self-gels at 37 °C and stabilizes both agents in the gel matrix. Based on the results of microbial colony assay and analysis of fibroblast growth kinetics, PEHHPG with ≥200 ppm of PHMB and ≥0.15 μg/mL of EGF can eradicate bacteria and enhance cell proliferation in vitro, illustrating the functionalities of PEHHPG. Given the aforementioned effects, together with the recognized advantages of injectable hydrogels such as wound shape/depth adaptation, low adhesiveness, exudate absorptiveness, and moisture maintenance, the developed PEHHPG is anticipated to be a feasible dressing material for deep wound treatment after further in vivo examinations.