The release of compounds and identification of the pathways involved in the cytotoxicity and xeno-estrogenicity of polymeric dental biomaterials utilized in Orthodontics and Paediatric Dentistry

Abstract

The objectives of the research included in this thesis were to qualitatively and quantitatively characterize the compounds released from dental composites utilized as pit and fissure sealants, orthodontic adhesives, polycarbonate brackets and aligners, in vitro (immersion media) and in vivo (salivary levels of eluents); investigate the biological reactivity of the molecules released with reference to cytotoxicity and xeno-estrogenic action; and describe the development and testing of alternative monomers, which are synthesized either without a benzoic ring or with an aromatic component, which is not derived from a process which uses BPA as a precursor. The study of the aforementioned variables included analytical instrumentation for the characterization of organic eluents (mainly liquid chromatography, mass spectroscopy, and Fourier transform infrared spectroscopy) and inorganic particulates (scanning electron microscopy coupled with Energy dispersive microanalysis), as well as standard assays for the assessment of DNA proliferation and viability of cells, and a cell culture model for the assessment of xeno-estrogenicity of the released species. The results demonstrated that residual Bis-GMA and TEGDMA monomers and BPA can be identified in laboratory immersion media and in rinsing media of patients, at concentrations, which range between some ppb and ppm, depending on the ageing status of the materials. Evidence was provided that copious rinsing after bonding resulted in baseline BPA concentration. The amount of BPA released ranged in most in vitro assays within the dietary intake, however, these levels have been found sufficient to induce xeno-estrogenicity in an estrogen-responsive cell culture, thus implying a potential concern of xeno-estrogenic action. Conventional cytotoxicity indicated a reduction in the proliferation rate of human gingival fibroblasts by delaying them at the G2 phase of the cell cycle, and in the sustained production of reactive oxygen species. The assessment of the feasibility of introducing existing monomers with linear carbon chains and without benzoic ring, or with aromatic rings, which are not derived from BPA, has proven successful in proposing candidates with conversion rates and mechanical properties comparable to established materials.

Date of Award	1 Aug 2019
Original language	English
Awarding Institution	The University of Manchester