pH Responsive Antibacterial Hydrogel Utilizing Catechol-Boronate Complexation Chemistry.

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.

Antimicrobial Property of Halogenated Catechols.

Bacterial infection associated with multidrug resistance (MDR) bacteria is increasingly becoming a significant public health risk. Herein, we synthesized a series of halogenated dopamine methacrylamide (DMA), which contains a catechol side chain modified with either chloro-, bromo-, or iodo-functional group. Catechol is a widely used adhesive moiety for designing bioadhesives and coating. However, the intrinsic antimicrobial property of catechol has not been demonstrated before. These halogenated DMA were incorporated into hydrogels, copolymers, and coatings and exhibited more than 99% killing efficiencies against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. More importantly, hydrogel containing chlorinated DMA demonstrated broad-spectrum antimicrobial activities towards multiple MDR bacteria, which included methicillin resistant S. aureus (MRSA), vancomycin resistant enterococci (VRE), multi antibiotics resistant Pseudomonas aeruginosa (PAER), multi antibiotics resistant Acinetobacter baumannii (AB) and carbapenem resistant Klebsiella pneumoniae (CRKP). These hydrogels also demonstrated the ability to kill bacteria in a biofilm while exhibiting low cytotoxic. Based on molecular docking and molecular dynamics simulation, Cl-functionalized catechol can potentially inhibit bacterial fatty acid synthesis at the enoyl-acyl carrier protein reductase (FabI) step. The combination of moisture-resistant adhesive property, inherent antimicrobial property, and the versatility of incorporating halogenated DMA into different polymeric materials greatly enhanced the potential for using these monomers for designing multifunctional bioadhesives and coatings.

In Situ Deactivation of Catechol-Containing Adhesive Using Electrochemistry.

Marine mussels secret catechol-containing adhesive proteins that enable these organisms to bind to various surfaces underwater. Synthetic mimics of these proteins have been created to function as adhesives and coatings for a wide range of applications. Here, we demonstrated the use of in situ electrical field stimulation to deactivate the adhesive property of catechol-containing adhesive that is in direct contact with a surface. Johnson-Kendall-Roberts (JKR) contact mechanics test was performed using a titanium (Ti) sphere in the presence of a pH 7.5 aqueous buffer. The Ti sphere also served as a conductive electrode for applying electricity to the adhesive, while a platinum (Pt) wire served as the counter electrode. Work of adhesion (Wadh) decreased with increased levels of applied voltage and current, exposure time to the applied electricity, and salt concentration of the interfacial buffer. Application of 9 V for 1 min completely deactivated the adhesive. UV-vis diffuse reflectance spectra and tracking of catechol oxidation byproduct, hydrogen peroxide, confirmed that catechol was oxidized as a result of applied electricity. Contact mechanics testing further confirmed that the Young's modulus of the adhesive increased by nearly 4 folds at the interface as a result of oxidative cross-linking, even though the modulus of the bulk of the adhesive was unaffected by applied electricity. The accumulation of hydroxyl ions near the cathode increased the local solution pH, which promoted oxidation-induced cross-linking of catechol and subsequently decreased its adhesive property. Tuning adhesive properties through in situ electrochemical oxidation provides on-demand control over the adhesive, which will potentially add another dimension in designing synthetic mimics of mussel adhesive proteins.