Toxicological Assessment of Photopolymers in Additive Manufacturing Using the Innovative Zebrafish Embryo Model

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George, Roy

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Walsh, Laurence

Love, Robert

Fidan, Ismail

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2018-07
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Abstract

The capacity of additive manufacturing technologies to initiate speedy polymerization of solvent-free resins accounts for their utility in the construction of medical devices. Nonetheless, biocompatibility is an issue of concern owing to the paucity of information on the biological risks of the materials and, inter alia, the unique parameters of the additive processes, which can influence the clinical properties of medical devices. With standards for preclinical evaluation lagging far behind emerging technologies, the onus is on academia and the materials science community to ascertain the biocompatibility of new materials if patient safety is to be guaranteed. In this doctoral project, additively manufactured (meth)acrylates for medical devices were subjected to biological evaluation using the innovative zebrafish embryo model, which is providing a high potential for toxicity profiling and has high genetic similarity to humans. Toxicological data indicate that the gradations of lethal, sublethal and teratogenic effects elicited in different exposure scenarios were influenced primarily by physicochemical characteristics of the materials, before and after ethanol treatment. Although characterization of methacrylates for unreacted carbon=carbon double bonds using Fourier transform infrared spectroscopy showed limited correlations between conversion rate and biological performance, ethanol-treated methacrylates induced a relatively low toxicity in zebrafish bioassays possibly due to decreased chemical constituents as observed by headspace gas chromatography-mass spectrometry. To strengthen research on photopolymers in additive manufacturing, quantitative analysis of the observed chemical compounds and their throughput in zebrafish bioassays are recommended for further study, taking into consideration that resin formulations are constantly evolving to meet the requirements for medical devices. While it is generally accepted that the zebrafish excels as a model system for developmental toxicity, a further examination of its utility in this novel project using different protocols provides basis for its consideration and adoption at a crucial when there is a lack of consensus regarding the most suited biological assessment methods for medical devices. Furthermore, the presence of potentially toxic acrylic esters other than residual methyl methacrylate underscores the need for standards revision to reflect the current trends in biomaterials and technological advancements.

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Thesis (PhD Doctorate)

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Doctor of Philosophy (PhD)

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School of Dentistry&Oral Hlth

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The author owns the copyright in this thesis, unless stated otherwise.

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Subject

Dentistry

Materials engineering

Analytical chemistry

Biochemistry and cell biology

Biomedical engineering

Toxological assessment

Photopolymers

Additive manufacturing

Zebrafish embryo model

Solvent-free resins

Medical devices

Toxicity profiling

Biomaterials

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