A NOVEL 2D DIPHOSPHATE NANOCRYSTALLINE HYDROGEL FOR SKIN INFECTIONS AND OTHER BIOMEDICAL APPLICATIONS

Abstract

Antimicrobial resistance, coupled with the limitations of polymer-based wound dressings, has intensified the need for sustainable, biocompatible topical materials capable of controlling infection while supporting tissue repair. This dissertation presents an entirely inorganic, polymer-free magnesium phosphate (MgP) nanosheet hydrogel as a thixotropic platform for dermal applications and demonstrates how rational ionic engineering can tune its physicochemical stability and biological performance. A pristine MgP nanosheet hydrogel was established as the core platform and characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, zeta potential analysis, and rheology, confirming a nanocrystalline two-dimensional architecture with shear-responsive gelation. Pristine MgP exhibited dose-dependent antimicrobial activity in vitro against Staphylococcus aureus, Escherichia coli, and Candida albicans, supported by ultrastructural evidence of microbial disruption. The formulation demonstrated excellent dermal compatibility in an OECD Test Guideline 439 reconstructed human epidermis model and in vivo topical tolerance studies. Functionally, pristine MgP significantly accelerated wound closure in non-infected full-thickness wounds but did not improve healing in Pseudomonas aeruginosa-infected wounds, indicating that bacterial burden limits its therapeutic efficacy. To further modulate antibacterial performance and stability, the MgP platform was systematically engineered through ionic incorporation. Zinc substitution preserved the nanosheet structure and enhanced antibacterial activity against S. aureus in vitro while maintaining dermal compatibility. In parallel, incorporation of pyrophosphate markedly improved colloidal and thermal stability and strengthened antibacterial activity against both S. aureus and P. aeruginosa. Building on this stabilized network, silver was introduced to generate MgP-pyrophosphate-Ag hydrogels with robust bactericidal activity against Gram-positive and Gram-negative pathogens, including P. aeruginosa, without inducing dermal irritation. Critically, silver-doped MgP-pyrophosphate hydrogels significantly restored wound closure in P. aeruginosa-infected wounds. Collectively, this work establishes a sustainable, polymer-free two-dimensional nanosheet hydrogel system whose physicochemical stability and biological function can be rationally tuned through ionic design, enabling an infection-responsive wound-care platform with potential biomedical and cosmetic applications.