pH-Responsive Antibacterial Resin Adhesives for Secondary Caries Inhibition

Secondary caries caused by dental plaque is one of the major reasons for the high failure rate of resin composite restoration. Although antimicrobial agent–modified dental restoration systems have been researched for years, few reported intelligent anticaries materials could respond to the change of the oral environment and help keep oral eubiosis. Herein, we report tertiary amine (TA)–modified resin adhesives (TA@RAs) with pH-responsive antibacterial effect to reduce the occurrence of secondary caries. Two kinds of newly designed TA monomers were synthesized: DMAEM (dodecylmethylaminoethyl methacrylate) and HMAEM (hexadecylmethylaminoethyl methacrylate). In the minimum inhibitory concentration and minimum bactericidal concentration test against Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii, they exhibited antibacterial effect only in acidic medium, which preliminarily verified the acid-activated effect of TAs. Then DMAEM and HMAEM were incorporated into adhesive resin at the mass fraction of 5%, yielding TA@RAs. In vivo and in vitro tests showed that the mechanical properties and biocompatibility of the adhesive were not affected. A S. mutans biofilm model in acidic and neutral medium was used and confirmed that TA@RAs could respond to the critical pH value of de-/remineralization and acquire reversible antibiofilm effect via the protonation and deprotonation of TAs. Meanwhile, the stability of antibacterial effect was confirmed via a 5-d pH-cycling experiment and a saliva-derived biofilm aging model. Furthermore, 16S rRNA gene sequencing showed that TA@RAs could increase the diversity of the saliva-derived biofilms, which implied that the novel materials could help regulate the microbial community to a healthy one. Finally, an in vitro demineralization model and in vivo secondary caries model were applied and demonstrated that TA@RAs could prevent secondary dental caries effectively. In summary, the reversible pH-responsive and non–drug release antibacterial resin adhesives ingeniously overcome the defect of the present materials and hold great promise for clinical application.