Toxicological assessment of additively manufactured methacrylates for medical devices in dentistry

Alifui-Segbaya, F., Bowman, J., White, A.R., Varma, S., Lieschke, G.J., George, R.
Acta biomaterialia   78: 64-77 (Journal)
Registered Authors
Lieschke, Graham J., Varma, Sony
3D printing, Biocompatibility, additive manufacturing, double bond conversion, methacrylates, zebrafish embryo model
MeSH Terms
  • Animals
  • Biological Assay
  • Dentistry*
  • Dentures
  • Embryo, Nonmammalian/drug effects
  • Endpoint Determination
  • Equipment and Supplies*
  • Larva/drug effects
  • Methacrylates/toxicity*
  • Toxicity Tests*
  • Zebrafish/embryology
30099197 Full text @ Acta Biomater
The paucity of information on the biological risks of photopolymers in additive manufacturing or three-dimensional printing (3DP) is a major challenge for the uptake of the technology in the construction of medical devices in dentistry. In this paper, the biocompatibility of additively manufactured methacrylates are evaluated using the innovative zebrafish (Danio rerio) embryo model. Data obtained confirmed gradations of toxicity primarily influenced by ethanol treatment, exposure scenarios, and extraction vehicles. In direct exposure tests, zebrafish (AB/Tü) embryos cultured on materials with ultrapure water showed accelerated toxicological effects compared to counterparts in transparent E3 medium. Similarly, toxic extracts induced mostly acute responses rather than cumulative chronic as observed in direct exposure. FTIR spectra was used to quantify the double bond conversion of the materials and those with >60 % BisEMA displayed relatively low degree of conversion; however, they were safe in zebrafish bioassays after ethanol treatment in contrast to untreated methacrylates. The study affirms that biocompatibility was influenced primarily by the physico-chemical characteristics, which subsequently influenced their residual monomer content before and after ethanol treatment. Given the precautionary implications of the study, we propose a 3-tiered approach i.e. using approved materials, apposite manufacturing parameters and post-processing techniques that together guarantee optimal results for all medical devices.
This study is timely and relevant since there is limited published literature that precisely describes the toxicological properties of additively manufactured methacrylates despite their increased popularity 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 study using different protocols provides basis for its consideration and adoption at a crucial time when there is a lack of consensus regarding the most suited biological assessment methods for medical devices.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes