Mechanically robust, mouldable, dynamically crosslinked hydrogel flap with multiple functionalities for accelerated deep skin wound healing

Abstract

Deep cutaneous wounds, which are difficult to heal and specifically occur on dynamic body surfaces, remain a substantial healthcare challenge in clinical practice because of multiple underlying factors, including excessive reactive oxygen species, potential bacterial infection, and extensive degradation of the extracellular matrix (ECM) which further leads to the progressive deterioration of the wound microenvironment. Any available individual wound therapy, such as antibiotic-loaded cotton gauze, cannot address all these issues. Engineering an advanced multifunctional wound dressing is the current need to promote the overall healing process of such wounds. Here, we report a multifunctional hydrogel flap primarily composed of biodegradable polymers gelatin (G) and poly-methyl vinyl ether-alt-maleic acid (MA) as the base material. The hydrogel physically incorporates tannic acid (TA) and vancomycin (V), for added functionality. The resulting hydrogel flap, gelatin- poly-methyl vinyl ether-alt-maleic acid-tannic acid-vancomycin (G-MA-TA-V/E-N), is formed through a chemical crosslinking process using EDC (E) and NHS (N). Thus, the hydrogel flap reveals multiple ideal properties that support its ease of application, including stretchability, porous microstructure (honey-comb structure), mouldability, and adhesiveness to multiple surfaces, including wet biological surfaces. The in vitro studies demonstrated strong antioxidant, antibacterial, and absorption properties essential for accelerated wound-healing applications. In vivo studies further reveal accelerated wound contraction and enhanced healing kinetics, promoting re-epithelialization, angiogenesis, and formation of apocrine glands. These findings underscore the efficacy and cost-effectiveness of fabricated hydrogel flaps as viable therapeutic options for treating deep skin wounds and make it worthwhile to integrate them with medical devices for tissue adhesion.