Synthesis of polymerizable betulin maleic diester derivative for dental restorative resins with antibacterial activity

Objective: Bisphenol A glycidyl methacrylate (Bis-GMA) is of great importance for dental materials as the preferred monomer. However, the presence of bisphenol-A (BPA) core in Bis-GMA structure causes potential concerns since it is associated with endocrine diseases, developmental abnormalities, and cancer lesions. Therefore, it is desirable to develop an alternative replacement for Bis-GMA and explore the intrinsic relationship between monomer structure and resin properties. Methods: Here, the betulin maleic diester derivative (MABet) was synthesized by a facile esterification reaction using plant-derived betulin and maleic anhydride as raw materials. Its chemical structure was confirmed by 1H and 13C NMR spectra, FT-IR spectra, and HR-MS, respectively. The as-synthesized MABet was then used as polymerizable comonomer to partially or completely substitute Bis-GMA in a 50:50 Bis-GMA: TEGDMA resin (5B5T) to formulate dental restorative resins. These were then determined for the viscosity behavior, light transmittance, real-time degree of conversion, residual monomers, mechanical performance, cytotoxicity, and antibacterial activity against Streptococcus mutans (S. mutans) in detail. Results: Among all experimental resins, increasing the MABet concentration to 50 wt% made the resultant 5MABet5T resin have a maximum in viscosity and appear dark yellowish after polymerization. In contrast, the 1MABet4B5T resin with 10 wt% MABet possessed comparable shear viscosity and polymerization conversion (46.6 +/- 1.0% in 60 s), higher flexural and compressive strength (89.7 +/- 7.8 MPa; 345.5 +/- 14.4 MPa) to those of the 5B5T control (48.5 +/- 0.6%; 65.7 +/- 6.7 MPa; 223.8 +/- 57.1 MPa). This optimal resin also had significantly lower S. mutans colony counts (0.35 x108 CFU/mL) than 5B5T (7.6 x108 CFU/mL) without affecting cytocompatibility. Significance: Introducing plant-derived polymerizable MABet monomer into dental restorative resins is an effective strategy for producing antibacterial dental materials with superior physicochemical property.