Ultrasound-Assisted Polyphenol Hydrogelation: Mechanistic Insights into Self-Assembly, Antioxidant, and Dual Antibacterial Action against Gram-Positive and Gram-Negative Pathogens

Engineering the self-assembly of bioactive natural molecules has always been a lucrative topic of research for different biomedical applications. In spite of the prominent bioactivity of polyphenolic molecules, their utilization has been mainly limited to that of cosolute or cobuilding block material. Here, we report the self-assembly formation by a naturally occurring polyphenolic molecule, methyl gallate, toward a therapeutic supramolecular hydrogel. The process follows nucleation kinetics, followed by the elongation of the fibrillar architecture. Interestingly, the introduction of ultrasound significantly reduces the gelation time. A suite of spectroscopic techniques has been employed to delve into the underlying interactions behind assembly formation. The morphological information was captured by utilizing electron microscopy (FEG-SEM) and atomic force microscopy (AFM). Furthermore, exploiting fluorescence lifetime imaging microscopy (FLIM) provides a better understanding of the secondary nucleation pathway. Molecular dynamics simulation provides time-evolved atomistic insight into the participating groups and the underlying forces that govern assembly formation. This hydrogel shows a spectrum of bioactivity, encompassing sustained release and antioxidant nature to bio- and hemo-compatibility. Furthermore, this hydrogel provides dual antibacterial activity toward both Gram-positive (<i>S. aureus</i>) and Gram-negative (<i>E. coli</i>) bacteria, making it a promising candidate for addressing the global challenge against bacterial infections.