Bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) causes acidic microenvironment during infection. A biomaterial that exhibits tunable antimicrobial property in a pH dependent manner is potentially attractive. Herein, we presented a novel antibacterial hydrogel consisting of pH responsive and reversible catechol-boronate linkage formed between intrinsically bactericidal chlorinated catechol (catechol-Cl) and phenylboronic acid. Fourier transformed infrared spectroscopy (FTIR), oscillatory rheometry, and Johnson Kendall Roberts (JKR) contact mechanics testing confirmed the formation and dissociation of the complex in a pH dependent manner. When the hydrogel was treated with an acidic buffer (pH 3), the hydrogel exhibited excellent antimicrobial property against multiple strains of Gram-positive and negative bacteria including MRSA (up to 4 log10 reduction from 108 colony forming units/mL). At an acidic pH, catechol-Cl was unbound from the phenylboronic acid and available for killing bacteria. Conversely, when the hydrogel was treated with a basic buffer (pH 8.5), the hydrogel lost its antimicrobial property but also became non-cytotoxic. At a basic pH, the formation of catechol-boronate complex effectively reduce the exposure of the cytotoxic catechol-Cl to the surrounding. When further incubating the hydrogel in an acidic pH, the reversible complex dissociated to re-expose catechol-Cl and the hydrogel recovered its antibacterial property. Overall, the combination of catechol-Cl and phenylboronic acid provide a new strategy for designing hydrogels with pH responsive antibacterial activity and reduced cytotoxicity.
Keywords: antibacterial; attenuated cytotoxicity; catechol–boronate complexation; halogenated catechol; pH responsive.