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Sci Rep. 2018 Sep 14;8(1):13818. doi: 10.1038/s41598-018-32313-5.

Transgenic zebrafish model for quantification and visualization of tissue toxicity caused by alloying elements in newly developed biodegradable metal.

Author information

1
Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK.
2
Center for Biomaterials, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
3
NuclixBio, Seoul, 08380, Republic of Korea.
4
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA.
5
Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea.
6
Laboratory for Biomaterials and Bioengineering, CRC-I, Department Min-Met-Materials Engineering & CHU de Québec Research Center, Laval University, Quebec City, Canada.
7
Center for Biomaterials, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea. chany@kist.re.kr.
8
Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea. chany@kist.re.kr.
9
Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK. james.edwards@ndorms.ox.ac.uk.

Abstract

The cytotoxicity of alloying elements in newly developed biodegradable metals can be assessed through relatively low-cost and rapid in vitro studies using different cell types. However, such approaches have limitations; as such, additional investigations in small mammalian models are required that recapitulate the physiological environment. In this study, we established a zebrafish (Danio rerio) model for cytotoxicity evaluations that combines the physiological aspects of an animal model with the speed and simplicity of a cell-based assay. The model was used to assess the cytotoxicity of five common alloying elements in biodegradable implant materials. Conventional in vitro testing using heart, liver, and endothelial cell lines performed in parallel with zebrafish studies revealed statistically significant differences in toxicity (up to 100-fold), along with distinct changes in the morphology of the heart, liver, and blood vessels that were undetectable in cell cultures. These results indicate that our zebrafish model is a useful alternative to mammalian systems for accurately and rapidly evaluating the in vivo toxicity of newly developed metallic materials.

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