Bis-quaternary ammonium betulin-based dimethacrylate: synthesis, characterization, and application in dental restorative resins

Secondary caries is the most common reason for restoration failures in general dental practices, resulting from tooth-adherent cariogenic bacteria in the oral environment. The application of polymerizable quaternary ammonium monomers (QAMs), which are capable of copolymerizing with methacrylate monomers and immobilizing antimicrobials in dental materials simultaneously, is expected to be an attractive anticaries strategy. In this work, three types of bis-quaternary ammonium betulin-based dimethacrylate derivatives (Bis-QADM-Bet) were synthesized via a Menschutkin reaction. Their chemical structures mainly differ for alkyl chain lengths of 4, 8, and 12 carbons (namely C4, C8, and C12). We focused on the fabrication of dental resins with 10 wt% Bis-QADM-Bet and a conventional dimethacrylate-based resin (bisphenol A glycerolate dimethacrylate/tri(ethyleneglycol) dimethacrylate, Bis-GMA/TEGDMA). The relationship between the Bis-QADM-Bet structure and the antibacterial activity, physicochemical properties, and cytotoxicity of dental resins were systematically investigated. The results indicated that regulating the alkyl chain length of Bis-QADM-Bet to C8 led to the formulated resin with superior effectiveness in terms of S. mutans inhibition (p < 0.05). Interestingly, this optimal resin exhibited better flowability and lower cytotoxicity in comparison with the Bis-GMA/TEGDMA based resin without compromising the mechanical properties (p > 0.05). Additionally, the potential antibacterial mechanism of contact-killing was proposed to illustrate the structural-morphological changes of S. mutans. In summary, this work shows that dental restorative resins containing Bis-QADM-Bet with the appropriate alkyl chain length are beneficial toward inhibiting the growth of S. mutans without sacrificing physicochemical performance.

Automated summary

Secondary caries resulting from tooth-adherent cariogenic bacteria is a common cause of restoration failures in dental practices. The use of polymerizable quaternary ammonium monomers (QAMs) to immobilize antimicrobials in dental materials is seen as a promising strategy for caries prevention. This study synthesized three types of quaternary ammonium betulin-based dimethacrylate derivatives and investigated their antibacterial activity, physicochemical properties, and cytotoxicity when incorporated into dental resins. The results showed that the derivative with an alkyl chain length of 8 carbons exhibited the most effective inhibition of S. mutans growth, while maintaining good flowability and low cytotoxicity.