Impact of the Polymerization Method on the Biocompatibility of Denture Base Resins in a 3D Tissue Engineered Human Oral Mucosa Model

by Viktor Martian
Doctoral thesis
Date of Examination:2025-03-31
Date of issue:2025-04-22
Advisor:Prof. Dr. Ralf Bürgers
Referee:Prof. Dr. Ralf Bürgers
Referee:Prof. Dr. Susanne Lutz
Sponsor:Deutsche Forschungsgemeinschaft: DFG
Persistent Address: http://dx.doi.org/10.53846/goediss-11217

 

 

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Abstract

English

Poly(methyl methacrylate) (PMMA) is widely used in dentistry to fabricate removable dentures. As these materials come into direct contact with the oral mucosa, biocompatibility is essential to prevent adverse reactions from residual monomers and other leachable substances. Biocompatibility is typically assessed following ISO standards using in vitro cell cultures in monolayers or in vivo models such as animal experiments. This study tested different PMMA materials for toxicity to human cells using various in vitro models, including an oral mucosa model (OMM). A detailed analysis of the materials and the obtained extracts by mass spectrometry revealed that different substances, such as the new plasticizer acetyl tributyl citrate (ATBC), were present in the materials, but only the monomer methyl methacrylate (MMA) leached out into the supernatant. Thereby, MMA leached out from all materials independent of the manufacturing process except the PMMA material, which was manufactured by photopolymerization. The obtained extracts were tested for their cytotoxicity in various models. For this purpose, standard ISO-norm experiments with mouse fibroblasts and immortalized keratinocytes originally derived from the oral mucosa were used. Complementary, an oral mucosa model composed of multilayered keratinocytes on top of a fibroblast-containing collagen matrix was created as part of this work, closely resembling the natural structure of native oral mucosa. By employing MTT assays, TUNEL assays, qPCRs and proteomics, it was shown that the extracts, a higher concentration of the monomer MMA and the plasticizer ATBC influenced the regulation of apoptotic genes, such as TNF, NF-κB, TP53, MMP1, CRK and RAB21 in the keratinocyte model and reduced the viability of the mouse fibroblasts. In contrast, this evident effect could not be overserved using the OMM system. Therefore, the toxicity of the extracts, MMA monomer and ATBC is model-dependent, limiting the ability to make general statements. Finally, this work demonstrated that methyl methacrylate can be released from dentures independently of the manufacturing process, except for the photopolymerized PMMA. The amount of released monomer seems to affect only simple cell models but not more complex, realistic models, such as the OMM. In the future, models like the OMM should be used to allow more precise statements on the toxicity of PMMA compounds.
Keywords: Dentures, PMMA, polymerization method, residual monomers, acetyl tributyl citrate, biocompatibility, 3D oral mucosa model, tissue engineering
 
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