A Bio-Hybrid ZnO Nanoplatform Functionalized with Antimicrobial Peptide/Protein Enhances Multimodal Bacterial Eradication and Accelerated Wound Healing

The increasing prevalence of bacterial infections, along with the persistence of biofilms and impaired wound healing, underscores the urgent need for advanced antimicrobial strategies. In the current study, ZnO nanoparticles (NPs) were synthesized by the sol–gel method and functionalized with PEG to improve the colloidal stability and biocompatibility. The PEG-functionalized ZnO NPs were then conjugated with the antimicrobial peptide nisin and the enzyme lysozyme to obtain two distinct nanoconjugates: nisin-PEG-ZnO and lysozyme-PEG-ZnO. Extensive physicochemical analyses, including Fourier-transform infrared (FT-IR), ultraviolet–visible (UV–vis) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), ζ-potential, dynamic light scattering (DLS), and thermogravimetric analysis (TGA), validated the successful synthesis of ZnO NPs and their efficient PEG-mediated surface functionalization. The antimicrobial potential of nanoconjugates against Escherichia coli and Staphylococcus epidermidis was investigated by evaluating the growth kinetics, antibiofilm formation, colony-forming units (CFU), minimum inhibitory and bactericidal concentrations. Among all the formulations, nisin-PEG-ZnO nanoconjugates showed better antibacterial activity, as well as antibiofilm activity, with significant cytoplasmic leakage of nucleic acids and proteins. The protein–protein interactions showed that nisin binds favorably with FtsZ, as well as lysozyme with MurA and OmpA, thereby confirming their antimicrobial activity. In addition, in vivo studies using a rat excision wound model showed that the nanoconjugates significantly accelerated wound closure with tissue regeneration, as confirmed by histopathological studies showing reduced inflammation with better tissue organization. The study confirmed that the nanoconjugates possess significant potential as effective antimicrobial agents for wound healing.