pH-Responsive ZnO Nanoparticle Wound Dressings for Targeted Antibacterial Therapy and Enhanced Healing

Infected wounds are an important concern in wound healing due to continuous colonization of bacteria, biofilm formation, and the emergence of antimicrobial resistance, which ultimately slows the healing process. In the present work, a pH-responsive wound dressing was designed by incorporating green-synthesized zinc oxide nanoparticles (ZnO NPs) into the chitosan/polyvinyl alcohol (PVA) matrix for effective antibacterial therapy and wound healing. Zinc oxide nanoparticles were successfully synthesized by using Azadirachta indica plant leaves as an eco-friendly reducing agent. Well-dispersed nanoparticles were obtained, ensuring effective control over their physicochemical properties. A wound dressing was successfully developed by incorporating ZnO nanoparticles into the chitosan/polyvinyl alcohol matrix. A pH-responsive wound dressing was developed, which showed increased ion release of Zn²⁺ at acidic pH (5.5), simulating an infected wound environment, while at the same time showing stability at neutral pH (7.4). This pH-responsive dressing showed increased antibacterial activity against both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli). It is worth noting that a high level of antibacterial activity of 90-95% was obtained due to the use of the developed pH-sensitive wound dressing. In addition, it possessed a significant level of antibiofilm activity capable of decreasing the amount of biofilm formation and disrupting microbe attachment. According to the results of the mechanism research, it is possible to state that the antibacterial properties were based on the synergic role of reactive oxygen species (ROS) production, Zn²⁺ ions releasing, and bacteria membranes impairment. As far as biocompatibility studies go, a high cell viability and insignificant hemolytic activity was determined, which shows that the developed structure is safe for biological applications. It is also important to note that in vitro experiments showed an enhancement in wound healing due to increased cell migration and rapid wound closure caused by the nanocomposite dressing. Significantly high antibacterial activity of around 90-95% was recorded using the pH-responsive wound dressing developed in the present study. The antibiofilm activity was also found to be high using the developed pH-responsive wound dressing. The antibacterial activity was found to be associated with the synergistic effect of the reactive oxygen species (ROS), the release of Zn²⁺ ions, and the damage to the cell membrane of the bacteria. The biocompatibility of the pH-responsive wound dressing was found to be high with high cell viability and low hemolytic activity. The in vitro wound healing assay was found to be associated with the improved cell migration using the nanocomposite material. The present study thus highlights the importance of the development of pH-responsive wound dressings using the green synthesis route with significant potential in the management of wounds.