Hyaluronate- and gelatin-based hydrogels encapsulating doxycycline as a wound dressing for burn injury therapy

Infection is a critical challenge in burn wound therapy. Wound dressings with antibacterial and multifunctional abilities associated with rapid burn wound healing are urgently needed. Here, we developed a bioadhesive and injectable ECM-mimicking hydrogel dressing with antibacterial capacity for burn injury therapy, which is crosslinked by dynamic boronate ester bonds between modified hyaluronate and gelatin (HG). The antibiotic doxycycline (Doxy) was encapsulated in HG networks for drug delivery around the wound sites. The HG/Doxy hydrogel dressing shows biocompatibility and antibacterial activity against Gram-positive and Gram-negative bacteria. Applying to a rat model of burn wound, the HG/Doxy hydrogel significantly speeds up wound closure by reducing the inflammatory reaction. Furthermore, the HG/Doxy hydrogel accelerates the regeneration of the skin structure by promoting collagen deposition, blood vessel regeneration, and hair follicle formation, eventually shortening the healing periods of burn wounds. These findings demonstrated the clinical potential of the HG/Doxy hydrogels as a promising burn wound dressing. STATEMENT OF SIGNIFICANCE: A bioadhesive and injectable hydrogel dressing has been developed for burn injury therapy. The ECM-mimicking hyaluronate-gelatin (HG) hydrogel with antibacterial ability is crosslinked by dynamic boronate ester bonds for delivering antibiotic doxycycline (Doxy). The HG/Doxy hydrogels exhibit bioadhesive, shape-adaptive, and water retention abilities in closing the irregular-shaped wound and providing a moist environment. The HG/Doxy hydrogels significantly shorten the healing periods of burn wounds in rat models within 10~14 days and promote the regeneration of skin structure, which have high potential for clinical applications.