Abstract
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Background: The increasing prevalence of antimicrobial resistance and delayed wound healing has intensified the demand for innovative, non-antibiotic topical therapies. Two-dimensional (2D) inorganic hydrogel systems have recently emerged as promising candidates due to their high surface reactivity, structural adaptability, and favorable safety profiles. However, their translational potential for combined antibacterial and wound-healing applications remains underexplored.
Aim: To develop and evaluate a 2D nanosheet-based inorganic hydrogel as a multifunctional topical platform with antibacterial activity and wound-healing potential.
Methods: The hydrogel was synthesized via controlled crystallization within a phosphate-based system to generate stable 2D nanosheet structures. Physicochemical characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM/EDX). Antibacterial activity was assessed in vitro against Staphylococcus aureus and Escherichia coli using quantitative reduction assays. Ultrastructural bacterial damage was examined using scanning and transmission electron microscopy (SEM/TEM). In vivo biocompatibility and wound-healing efficacy were evaluated using a BALB/c murine excisional wound model, with percentage wound closure measured over five days.
Results: The hydrogel demonstrated significant dose-dependent antibacterial activity, achieving at least a 10-fold reduction in S. aureus and over a 20-fold reduction in E. coli compared to untreated controls. Microscopic analyses revealed membrane disruption, structural deformation, and compromised cellular integrity in treated bacteria. No signs of erythema, edema, or irritation were observed in treated animals. Wound closure was significantly enhanced in the treatment group, reaching 46% by Day 5 compared to 37% in controls (p = 0.008), indicating accelerated early-stage tissue repair.
Conclusion: This study demonstrates that 2D inorganic nanosheet hydrogels can function as dual-action topical systems, combining antimicrobial efficacy with enhanced wound closure. These findings support further translational investigation of 2D hydrogel platforms as next-generation alternatives to conventional antibiotic-based wound care strategies.
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