10-methacryloyloxy-decyl-dihydrogen phosphate (10-MDP) mostly changed the bonding concept by chemically interacting with hydroxyapatite. Currently, multimode simplified universal dentin bonding systems (UDBSs) contains 10-MDP, and its use in etch-and rinse mode renewed the concern on the employment of antienzymatic agents as chlorhexidine (CHX). This study aimed to investigate the effect of MDP-CHX interaction on bonding properties. The following DBSs were tested: MP-Adper Scotchbond Multipurpose, SU-Adper Scothbond Universal, CSE-Clearfil SE Bond, and CPB–Clearfill Protect Bond. The degree of conversion (DC) was assessed by a drop of each DBS (≈3.0 μL, n = 3) combined with chlorhexidine diacetate (0, 0.2, and 2%) and hydroxyapatite (HAP) (0, 0.1%) using Fourier Transform Infrared Spectroscopy (FTIR). Bond strength (BS) was tested using 144 human third molars, randomized according to DBS/CHX groups (n = 12), and submitted to the microtensile test (μTBS) at 24-h, 6-month, and 12-month periods. Failure mode of interfaces, FTIR profile, and Scanning Electronic Microscopy (SEM) were assessed. DC and BS data were statistically analyzed by three-way and Repeated Measures ANOVA followed by Tukey tests (p < 0.05). Results: CHX decreased DC values of MDP-based systems, while HAP/CHX recovered DC values compared with control. CHX reduced BS values for CSE (MDP-based), while improved BS values for MP (MDP-free). MDP-based system associated particularly with 2% CHX should be avoided even for multimode simplified DBS, as both ingredients may compete for calcium, reducing their benefits.
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