Injectable and thermoresponsive hybrid hydrogel with Antibacterial, Anti-inflammatory, oxygen Transport, and enhanced cell growth activities for improved diabetic wound healing

Treatment of diabetic foot ulcer (DFU) remains a global challenge since it is often hindered by multiple unfavorable factors including hypoxia, impaired cell signaling, persistent infections, and prolonged inflammation during healing process. Therefore, developing a material that can address the aforementioned difficulties is highly on demand in the clinic nowadays. In this study, a new type of injectable and thermoresponsive hyaluronic acid (HA)/hexamethylene diisocyanate-Poloxamer 407 copolymer crosslinked hybrid hydrogel consisting of fluorocarbon nanodroplets (FNDs), epidermal growth factor-loaded chitosan nanoparticles (ENPs), and polyhexamethylene biguanide (PHMB) named FPE-HHPG was successfully developed for diabetic wound healing. The FPE-HHPG can be self-gelationed at 37 °C and offer multiple functions of oxygen supply, antibacterial, and enhanced cell growth which were contributed by the FNDs, PHMB, and ENPs, respectively. In addition, the FPE-HHPG can provide anti-inflammatory effects functioned by its entity constituent of high molecular weight HA. These functionalities allowed the FPE-HHPGs a markedly improved wound healing efficacy on diabetic rats including faster wound closure, thorough re-epithelialization, less inflammatory response, and rapid collagen deposition and maturation in comparison to the outcomes treated by using gauze or the commercial dressing HeraDerm. Given the aforementioned effectiveness together with known merits of injectable hydrogels such as moisture maintenance, wound shape adaptation, exudate absorptiveness, and low adhesiveness, the developed FPE-HHPG is anticipated to be a feasible tool for diabetic wound treatment in the clinic.