Nowadays, dental caries remains one of the most prevalent non-communicable diseases and poses serious global public health burden [1], [2]. Various restorative materials are available to replace the structure of decayed teeth [3], where resin-based composites have gained much attention in clinical practice due to their fascinating features, such as natural esthetics and excellent biocompatibility, and therefore represent as a popular choice for patients and dentists [4], [5]. Generally, methacrylate chemistry serves as the foundation for the organic matrix since 1960 s, where the degree of cross-linking of multiple methacrylates is essential for composite performance [6], [7]. Bisphenol A glycerolate dimethacrylate (Bis-GMA) is the preferred monomer utilized as the foundation for dental resin formulations due to its rigid bisphenol-A (BPA) core and two pendant hydroxyl groups, resulting in high viscosity (η = 1200 Pa.s) and low reaction mobility during the photo-polymerization [8]. In addition, the presence of BPA causes potential concerns since it is associated with various endocrine diseases, developmental abnormalities, and cancer lesions [9], [10], [11]. Although current research indicates that the short-term risk of estrogenic effects from Bis-GMA-based restorations is negligible [12], it is prudent to develop alternative replacements as a means of mitigating any possible safety risks associated with their long-term utilization and possible release of contaminants.

Plant-derived natural products are highly attractive due to their biocompatibility, biosafety, and multiple reactive groups that can be used for polymerizable functionalization [13], [14], [15]. Bioactive properties of natural products, including antibacterial and anti-inflammatory effects [16], [17], [18], make them interesting candidates for the design and preparation of multifunctional monomers for dental composite applications. For example, eugenol obtained from Eugenia caryophyllata could be functionalized with polymerizable methacrylate groups via Fisher esterification reaction [19]. The as-synthesized eugenol derivatives exhibited antibacterial activity against Streptococcus mutans (S. mutans) and good cellular proliferation, indicating that they were potentially efficacious for dental materials. Multi-methacrylated bile acid derivatives with adjustable viscosity, hydrophobicity, and reactivity were prepared and investigated for the effect of chemical structure on the degree of conversion, polymerization shrinkage, and the mechanical performance of the resulting polymers and dental composites [17]. Two dimethacrylate monomers derived from bio-based creosol were synthesized and further used to prepare the Bis-GMA-free resin matrix and resin composites to eliminate estrogenic activity [20]. These composites had higher double bond conversion, lower volumetric shrinkage, and lower cytotoxicity than those of Bis-GMA-based materials. Other bio-sourced chemicals, such as limonene and isosorbide, have also been reported as promising alternatives to BPA for the development of polymerizable monomers due to their rigidity and transparency [21], [22]. In our previous work, betulin, a naturally occurring triterpene isolated from the bark of birch trees, was successfully introduced to develop mono- and di-methacrylated betulin derivatives (M1Bet and M2Bet) as antibacterial comonomers for dental resins [23]. Results showed that 10 wt% M2Bet made the resulting resin possess higher transparency, improved polymerization rate, and lower S. mutans colony counts. However, the antibacterial activity should be further increased. In terms of chemical structures, the presence of COOH or COO- groups in monomers can influence the antibacterial property of the resulting resin materials through factors such as membrane disruption [24], [25], electrostatic interactions [26], [27], and improved surface wettability [28], [29], thus affecting the growth and viability of microorganisms. In addition, the relationship between the polymerizable structures of carboxyl-containing monomers and the physical-chemical properties of the resultant dental resins remains to be elucidated.

In this work, the betulin maleic diester derivative (MABet) was synthesized by the facile esterification reaction between betulin and maleic anhydride, where the filtration process was used to isolate and purify the product. The obtained MABet further served as a substitute for Bis-GMA in resin mixtures. The rheology behavior, light transmittance, conversion degree, mechanical performance, cytotoxicity, and antibacterial property of various resin formulations were explored in detail. All results were also compared to a Bis-GMA/TEGDMA (50/50, wt/wt) control. The objective of this work is to develop an alternative replacement for Bis-GMA and to explore the intrinsic relationship between monomer structure and resin properties. The introduction of MABet monomer into dental restorative resins should be an effective strategy for producing antibacterial dental materials with superior physicochemical property. The hypothesis is that higher MABet content produces dental resins with higher antibacterial activity at the detriment of light transmittance, polymerization conversion, and mechanical performance.