Poster N14 - Investigating flipped ester-based design and mesoporous cerium silicate nanoparticle to attenuate biodegradation in dental formulations

Introduction:

Objectives:
To investigate a novel flipped ester-based methacrylate monomer design and mesoporous cerium silicate (MPCeSi) nanoparticles (NPs) to resist biodegradation in dental composites.

Introduction:
Dental adhesive layer and class I-V restoration failure is an exponentially growing issue in dentistry. The primary cause of composite failure is hydrolysis of ester bond in methacrylate-based resin composite (consist of Ethylene glycol methacrylate (EGDMA) or triethylene glycol dimethacrylate (TEGDMA), hydrophilic monomers) as a result of exposure to saliva enzymes such as cholesterol esterase and pseudocholinesterase, localized acidic pH, and oral microbiome in the Dynamic Oral MicroEnvironment (DOME)[1–3]. The hydrolysis or biodegradation of ester-based methacrylate formulations results in leaching of unreacted monomers[4] as well as additional byproducts when exposed to DOME conditions [5–8]. These products have been associated with modulation biochemistry and gene expression of local oral microbiota [9,10]. There have been various strategies explored to control the degradation of dental formulation such as development of ether and ether-ester group-based monomers[2,11] and incorporation of nanoparticulate systems[12]. The aim of this study was to investigate the flipped ester-based acrylate monomers and mesoporous cerium silicate (MPCeSi) nanoparticles (NPs) to attenuate the biodegradation process thereby extending the longevity of resin-based adhesives, cements, and composites.

Materials and

Methods: The flipped ester group methacrylate monomer was supplied by TDA research Colorado, and the disc were prepared by mixing with photo/co-initiators using a PTFE mold. The 40µL monomer and photo/co-initiator mixture was cured for 40s at 1000mW/cm2. The MPCeSi NPs were synthesized by microemulsion method using CTAB as a template precursor in water and liquid ammonia at room temperature. The NPs were calcined to remove the CTAB and to obtain the mesoporous MPCeSi NPs. The NPs were characterized using TEM (size), nitrogen isotherm (porosity), and cytotoxicity (with fibroblast and keratinocyte cells) followed by alizarin red assay for matrix remineralization with Bone MSCs. The known concentration of NPs was mixed with TEGDMA and photo/co-initiator mixture. The discs were prepared as described previously[8,13–15]. The physical, mechanical, and surface properties of the discs prepared using flipped ester design and NPs-TEGDMA discs were assessed and compared with controls (EGDMA and TEGDMA). A 5-week cholesterol esterase (CE, 0.5units/ml) assay examined EGEMA and NPs-TEGDMA resistance to biodegradation.

Results, Conclusions, and Discussions:

Results:
The flipped ester design EGEMA polymer showed significantly lower weight or material loss (p=0.029), preserved the physical strength (p=0.0015), and reduced water sorption (p=0.0002) compared to EGDMA. While in the case of TEGDMA, mesoporous cerium silicate (MPCeSi) nanoparticles (NPs) supported a significant increase in degree of conversion (DC) at 1.0% filler concentration (1:10-56.72% and 4:10-53.88%) compared to pristine TEGDMA discs (48.81%), and biodegradation assay suggested significantly lower material loss in the presence of NPs. Also, MPCeSi NPs as filler in TEGDMA improved physical properties. The BET analysis calculated the total surface area as 654.63m2/g (1:10) and 515.91m2/g (4:10). Both the MPCeSi NP types were non-toxic to fibroblast and oral keratinocytes cells up to 300µg/ml concentration while MPCeSi NPs (4:10) showed a significant increase in intensity@405nm confirming matrix remineralization for bone marrow derived MSCs.

Conclusions:
It is high time to change the conventional methacrylate ester-based formulations in dental application because the ester group is prone to biodegradation. The flipped ester design preserved the physical and mechanical properties by preserving the polymer backbone which is released as a byproduct in traditional monomers like TEGDMA and BisGMA. Another approach to control biodegradation could be incorporation of nano-additives such as MPCeSi NPs which are biocompatible, anti-inflammatory, neutralize ROS, and support matrix remineralization. In addition, when mixed with TEGDMA, it significantly improves DC and hardness. MPCeSi NPs resistance to biodegradation encourages future investigation of MPCeSi-TEGDMA in clinical dental formulations.

Acknowledgements (Optional): This work was financially supported by the National Institute of Dental and Craniofacial Research (NIH) through grant number 5R44DE024013-03 (partially), as well as by the School of Dentistry Faculty Start-up Fund at the University of Minnesota.