Assessment of the biocompatibility of three-dimensional-printed polymers using multispecies toxicity tests

Zhu, Feng; Friedrich, Timo; Nugegoda, Dayanthi; Kaslin, Jan; Wlodkowic, Donald

doi:10.1063/1.4939031

Cited by 54 publications

(55 citation statements)

References 18 publications

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“…WaterShed becomes yellow under prolonged exposure to ambient light 10 . Moreover, a recent systematic investigation has shown that many of the popular 3D-printing resins (including Visijet Crystal or WaterShed) release toxic leachates that inhibit growth of cells from different vertebrate and invertebrate indicator organisms 19 . Zebrafish embryos cultured on these resins showed developmental defects 20 .…”

Section: Introductionmentioning

confidence: 99%

3D-printing of transparent bio-microfluidic devices in PEG-DA

et al. 2016

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The vast majority of microfluidic systems are molded in poly(dimethylsiloxane) (PDMS) by soft lithography due to the favorable properties of PDMS: biocompatible, elastomeric, transparent, gas-permeable, inexpensive, and copyright-free. However, PDMS molding involves tedious manual labor, which makes PDMS devices prone to assembly failures and difficult to disseminate to research and clinical settings. Furthermore, the fabrication procedures limit the 3D complexity of the devices to layered designs. Stereolithography (SL), a form of 3D-printing, has recently attracted attention as a way to customize the fabrication of biomedical devices due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. However, existing SL resins are not biocompatible and patterning transparent resins at high resolution remains difficult. Here we report procedures for the preparation and patterning of a transparent resin based on low-MW poly(ethylene glycol) diacrylate (MW 250) (PEG-DA-250). The 3D-printed devices are highly transparent and cells can be cultured on PEG-DA-250 prints for several days. This biocompatible SL resin and printing process solves some of the main drawbacks of 3D-printed microfluidic devices: biocompatibility and transparency. In addition, it should also enable the production of non-microfluidic biomedical devices.

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Section: Introductionmentioning

confidence: 99%

3D-printing of transparent bio-microfluidic devices in PEG-DA

et al. 2016

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“…Although 'Rx' Visijet Crystal recorded almost 100% survival rates in Test 1 and Test 2, tests were concluded on day 2 due to the severity of sublethal and teratogenic effects observed in embryos. Previous studies 8,10) have also reported Visijet materials to be unsafe in zebrafish assays. Although it is not unusual for zebrafish under 120 hpf to spend most of their time lying inactively on the bottom of the tanks until the inflation of their swim bladder 24) , those exposed to AM materials showed increased lethargy or behavioural perturbations, which often precede mortality.…”

Section: Discussionmentioning

confidence: 99%

“…The quality of the AM-produced devices may consequently vary when identical parts are built using different 3D printers or even when the same 3D printer, parameters, process steps, and materials are used 2) . An issue of concern is recent studies highlighting their potential toxicity [8][9][10][11] . By being toxic, there is a relative ability of the materials to cause injury to biological tissues, ranging from improper biochemical function, organ damage, and cell destruction, to death 12) .…”

Section: Introductionmentioning

confidence: 99%

Biocompatibility of Photopolymers in 3D Printing

Alifui‐Segbaya

Varma

Lieschke

et al. 2017

3D Printing and Additive Manufacturing

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The biocompatibility of photopolymers in additive manufacturing (AM) often referred to as 3D printing (3DP) is an issue of concern due to, among other things, the unique parameters of the manufacturing process, which can influence the physical, chemical, and biological properties of AM-produced devices. The quality of AM-produced devices may consequently vary when identical parts are built using different 3D printers or even when the same 3D printer, parameters, process steps, and materials are used. In this novel study, representative materials built with stereolithography and material jetting processes were subjected to biological evaluation using the Organization for Economic Cooperation and Development (OECD) fish embryo test designed to determine acute toxicity of chemicals on embryonic stages of fish. The study demonstrates that the AM materials are toxic in zebrafish assays; however, the adverse effects of toxicity in some materials were reduced significantly after treatment with ethanol. Within the limitations of the study, it is evident that material composition and cleaning method are significant parameters by which the biological risks of photopolymers in 3DP can be assessed. Furthermore, the zebrafish biocompatibility assay is a reliable assessment tool for quantifying the toxicity of leachates in AM materials.

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“…Aqueous extracts from all SL polymers induced 100% mortality of Daphnia sp. neonates after 24 hours, and all SL and MJM polymers proved to be significantly toxic to zebrafish embryos 112 (Figure 9D). Zebrafish embryos cultured in 3D-printed structures made of Visijet Crystal or Watershed showed developmental defects 112,113 , whereas those grown in leachate extracts of ABS and PLA did not have any behavioral abnormalities 112 .…”

Section: Transition From Soft Lithography To 3d-printingmentioning

confidence: 99%

“…A couple of recent studies presented a comprehensive toxicity profiling of the leachates of some commercially available resins and polymers that are commonly used in 3D printing – ABS (FDM), PLA (FDM), VisiJet Crystal (MJM), Visijet SL Clear (MJM), Watershed 11122 XC (SL), Dreve Fototec 7150 Clear (SL), Form 1 Clear (SL) 112,113 . Zhu et al observed significant growth inhibition in freshwater microalgae when they were cultured for 48-96 hours in water-soluble leachate extracted from all 3D-printed structures 112 . Aqueous extracts from all SL polymers induced 100% mortality of Daphnia sp.…”

Section: Transition From Soft Lithography To 3d-printingmentioning

confidence: 99%

The upcoming 3D-printing revolution in microfluidics

et al. 2016

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In the last two decades, the vast majority of microfluidic systems have been built in poly(dimethylsiloxane) (PDMS) by soft lithography, a technique based on PDMS micromolding. A long list of key PDMS properties have contributed to the success of soft lithography: PDMS is biocompatible, elastomeric, transparent, gas-permeable, water-impermeable, fairly inexpensive, copyright-free, and rapidly prototyped with high precision using simple procedures. However, the fabrication process typically involves substantial human labor, which tends to make PDMS devices difficult to disseminate outside of research labs, and the layered molding limits the 3D complexity of the devices that can be produced. 3D-printing has recently attracted attention as a way to fabricate microfluidic systems due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. Resins with properties approaching those of PDMS are being developed. Here we review past and recent efforts in 3D-printing of microfluidic systems. We compare the salient features of PDMS molding with those of 3D-printing and we give an overview of the critical barriers that have prevented the adoption of 3D-printing by microfluidic developers, namely resolution, throughput, and resin biocompatibility. We also evaluate the various forces that are persuading researchers to abandon PDMS molding in favor of 3D-printing in growing numbers.

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Assessment of the biocompatibility of three-dimensional-printed polymers using multispecies toxicity tests

Cited by 54 publications

References 18 publications

3D-printing of transparent bio-microfluidic devices in PEG-DA

3D-printing of transparent bio-microfluidic devices in PEG-DA

Biocompatibility of Photopolymers in 3D Printing

The upcoming 3D-printing revolution in microfluidics

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