The future of skin toxicology testing–three-dimensional bioprinting meets microfluidics
Open accessAbstract
Over the years, the field of toxicology testing has evolved tremendously from the use of animal models to the adaptation of in vitro testing models. In this perspective article, we aim to bridge the gap between the regulatory authorities who performed the testing and approval of new chemicals and the scientists who designed and fabricated these in vitro testing models. An in-depth discussion of existing toxicology testing guidelines for skin tissue models (definition, testing models, principle, and limitations) is first presented to have a good understanding of the stringent requirements that are necessary during the testing process. Next, the ideal requirements of toxicology testing platform (in terms of fabrication, testing, and screening process) are then discussed. We envisioned that the integration of three-dimensional bioprinting within miniaturized microfluidics platform would bring about a paradigm shift in the field of toxicology testing; providing standardization in the fabrication process, accurate, and rapid deposition of test chemicals, real-time monitoring, and high throughput screening for more efficient skin toxicology testing.
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A study published in the Journal of Toxicology in Vitro (2022) demonstrated that a 3D human skin model accurately predicted skin compatibility of various sunscreen formulations, reducing the need for animal testing and providing more reliable safety assessments.
“For instance, a study published in the Journal of Toxicology in Vitro (2022) demonstrated the effectiveness of a 3D human skin model in assessing the safety of various sunscreen formulations. The model accurately predicted skin compatibility, reducing the need for animal testing and providing more reliable safety assessments (137).”
From The dark side of beauty: an in-depth analysis of the health hazards and toxicological impact of synthetic cosmetics and personal care products (2024) · cites this paper as [137]
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Cites
Microfluidic Large-Scale Integration
Thorsen, T., Maerkl, S. J., & Quake, S. R. (2002) · Science · doi:10.1126/science.1076996 · Cited by 2,223 · see citing works
From 3D cell culture to organs-on-chips
Huh, D., Hamilton, G. A., & Ingber, D. E. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.09.005 · Cited by 1,834 · see citing works
Three-dimensional cell culture: the missing link in drug discovery
Breslin, S., & O’Driscoll, L. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2012.10.003 · Cited by 1,332 · see citing works
Progress and opportunities for tissue-engineered skin
MacNeil, S. (2007) · Nature · doi:10.1038/nature05664 · Cited by 1,114 · see citing works
Bioink properties before, during and after 3D bioprinting
Hölzl, K., Lin, S., Tytgat, L., Vlierberghe, S. V., Gu, L., & Ovsianikov, A. (2016) · Biofabrication · doi:10.1088/1758-5090/8/3/032002 · Cited by 1,087 · see citing works
Bioinks for 3D bioprinting: an overview
Gungor-Ozkerim, P. S., Inci, I., Zhang, Y., Khademhosseini, A., & Dokmeci, M. (2018) · Biomaterials Science · doi:10.1039/c7bm00765e · Cited by 1,057 · see citing works
A definition of bioinks and their distinction from biomaterial inks
Gröll, J., Burdick, J. A., Cho, D.-W., Derby, B., Gelinsky, M., Heilshorn, S. C., Jüngst, T., Malda, J., Mironov, V. A., Nakayama, K., et al. (2018) · Biofabrication · doi:10.1088/1758-5090/aaec52 · Cited by 808 · see citing works
Design and Fabrication of Human Skin by Three-Dimensional Bioprinting
Lee, V., Singh, G., Trasatti, J. P., Bjornsson, C. S., Xu, X., Tran, T. N., Yoo, S., Dai, G., & Karande, P. (2013) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2013.0335 · Cited by 728 · see citing works
Toxicology for the twenty-first century
Härtung, T. (2009) · Nature · doi:10.1038/460208a · Cited by 665 · see citing works
Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds
Skardal, A., Mack, D. L., Kapetanovic, E., Atala, A., Jackson, J. D., Yoo, J. J., & Söker, S. (2012) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0088 · Cited by 663 · see citing works
Organs-on-a-Chip: A Fast Track for Engineered Human Tissues in Drug Development
Ronaldson-Bouchard, K., & Vunjak-Novakovic, G. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.02.011 · Cited by 657 · see citing works
Michael, S., Sorg, H., Peck, C., Koch, L., Deiwick, A., Chichkov, B. N., Vogt, P. M., & Reimers, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057741 · Cited by 625 · see citing works
Skin tissue generation by laser cell printing
Koch, L., Deiwick, A., Schlie, S., Michael, S., Gruene, M., Coger, V., Zychlinski, D., Schambach, A., Reimers, K., Vogt, P. M., et al. (2012) · Biotechnology and Bioengineering · doi:10.1002/bit.24455 · Cited by 611 · see citing works
Lee, W., Debasitis, J., Lee, V. K., Lee, J.-H., Fischer, K., Edminster, K. R., Park, J., & Yoo, S.-S. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2008.12.009 · Cited by 576 · see citing works
Engineering alginate as bioink for bioprinting
Jia, J., Richards, D., Pollard, S., Tan, Y. J., Rodriguez, J., Visconti, R. P., Trusk, T. C., Yost, M. J., Yao, H., Markwald, R. R., et al. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.06.034 · Cited by 551 · see citing works
Albanna, M., Binder, K. W., Murphy, S. V., Kim, J. H., Qasem, S. A., Zhao, W., Tan, J., El-Amin, I. B., Dice, D. D., Marco, J., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-38366-w · Cited by 519 · see citing works
Integration of Cell Culture and Microfabrication Technology
Park, T., & Shuler, M. (2003) · Biotechnology progress (Print) · doi:10.1021/bp020143k · Cited by 495 · see citing works
3D bioprinting of functional human skin: production and in vivo analysis
Cubo, N., García, M., del Cañizo, J. F., Velasco, D., & Jorcano, J. L. (2016) · Biofabrication · doi:10.1088/1758-5090/9/1/015006 · Cited by 458 · see citing works
Life is 3D: Boosting Spheroid Function for Tissue Engineering
Laschke, M. W., & Menger, M. D. (2016) · Trends in biotechnology · doi:10.1016/j.tibtech.2016.08.004 · Cited by 442 · see citing works
Human Skin 3D Bioprinting Using Scaffold‐Free Approach
Pourchet, L. J., Thepot, A., Albouy, M., Courtial, E. J., Boher, A., Blum, L. J., & Marquette, C. A. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201601101 · Cited by 352 · see citing works
Engineering an in vitro air-blood barrier by 3D bioprinting
Horváth, L., Umehara, Y., Jud, C., Blank, F., Petri‐Fink, A., & Rothen‐Rutishauser, B. (2015) · Scientific Reports · doi:10.1038/srep07974 · Cited by 349 · see citing works
The use of skin models in drug development
Mathes, S. H., Ruffner, H., & Graf‐Hausner, U. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.12.006 · Cited by 321 · see citing works
Lilienblum, W., Dekant, W., Foth, H., Gebel, T., Hengstler, J. G., Kahl, R., Kramer, P.-J., Schweinfurth, H., & Wollin, K. (2008) · Archives of Toxicology · doi:10.1007/s00204-008-0279-9 · Cited by 315 · see citing works
Sun, T. L., Jackson, S. J., Haycock, J. W., & MacNeil, S. (2006) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2005.12.021 · Cited by 309 · see citing works
Polyelectrolyte gelatin-chitosan hydrogel optimized for 3D bioprinting in skin tissue engineering
Ng, W. L., Yeong, W. Y., & Naing, M. W. (2016) · International Journal of Bioprinting · doi:10.18063/ijb.2016.01.009 · Cited by 294 · see citing works
Self-citationKim, B. S., Gao, G., Kim, J. Y., & Cho, D. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201801019 · Cited by 292 · see citing works
Print Me An Organ! Why We Are Not There Yet
Ng, W. L., Chua, C. K., & Shen, Y. (2019) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2019.101145 · Cited by 292 · see citing works
Self-citationLee, W., Lee, V., Polio, S. R., Keegan, P., Lee, J., Fischer, K., Park, J., & Yoo, S. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22613 · Cited by 289 · see citing works
Mosadegh, B., Kuo, C., Tung, Y., et al. (2010) · Nature Physics · doi:10.1038/nphys1637 · Cited by 288 · see citing works
Direct 3D cell-printing of human skin with functional transwell system
Kim, B. S., Lee, J., Gao, G., & Cho, D. (2017) · Biofabrication · doi:10.1088/1758-5090/aa71c8 · Cited by 286 · see citing works
Microfluidics for cell-based high throughput screening platforms—A review
Du, G., Fang, Q., & den Toonder, J. M. J. (2016) · Analytica Chimica Acta · doi:10.1016/j.aca.2015.11.023 · Cited by 276 · see citing works
Pumpless microfluidic platform for drug testing on human skin equivalents
Abaci, H. E., Gledhill, K., Guo, Z., Christiano, A. M., & Shuler, M. L. (2014) · Lab on a Chip · doi:10.1039/c4lc00999a · Cited by 267 · see citing works
Organ-Derived Decellularized Extracellular Matrix: A Game Changer for Bioink Manufacturing?
Choudhury, D., Tun, H. W., Wang, T., & Naing, M. W. (2018) · Trends in biotechnology · doi:10.1016/j.tibtech.2018.03.003 · Cited by 265 · see citing works
Full-thickness human skin-on-chip with enhanced epidermal morphogenesis and barrier function
Sriram, G., Alberti, M., Dancik, Y., Wu, B., Wu, R., Feng, Z., Ramasamy, S., Bigliardi, P. L., Bigliardi‐Qi, M., & Wang, Z. (2017) · Materials Today · doi:10.1016/j.mattod.2017.11.002 · Cited by 258 · see citing works
Grover, W. H., Ivester, R. H. C., Jensen, E. C., et al. (2006) · Lab on a Chip · doi:10.1039/b518362f · Cited by 254 · see citing works
Skin Bioprinting: Impending Reality or Fantasy?
Ng, W. L., Wang, S., Yeong, W. Y., & Naing, M. W. (2016) · Trends in biotechnology · doi:10.1016/j.tibtech.2016.04.006 · Cited by 251 · see citing works
Self-citationProof-of-concept: 3D bioprinting of pigmented human skin constructs
Ng, W. L., Qi, J. T. Z., Yeong, W. Y., & Naing, M. W. (2018) · Biofabrication · doi:10.1088/1758-5090/aa9e1e · Cited by 244 · see citing works
Self-citation3D bioprinting of skin: a state-of-the-art review on modelling, materials, and processes
Vijayavenkataraman, S., Lu, W. F., & Fuh, J. (2016) · Biofabrication · doi:10.1088/1758-5090/8/3/032001 · Cited by 232 · see citing works
Microvalve-based bioprinting – process, bio-inks and applications
Ng, W. L., Lee, J. M., Yeong, W. Y., & Naing, M. W. (2017) · Biomaterials Science · doi:10.1039/c6bm00861e · Cited by 231 · see citing works
Self-citationBioprinting of biomimetic skin containing melanocytes
Min, D., Lee, W., Bae, I., Lee, T. R., Croce, P., & Yoo, S. (2017) · Experimental Dermatology · doi:10.1111/exd.13376 · Cited by 191 · see citing works
The arrival of commercial bioprinters – Towards 3D bioprinting revolution!
Choudhury, D., Anand, S., & Naing, M. W. (2024) · International Journal of Bioprinting · doi:10.18063/ijb.v4i2.139 · Cited by 189 · see citing works
Mazzocchi, A. R., Söker, S., & Skardal, A. (2019) · Applied Physics Reviews · doi:10.1063/1.5056188 · Cited by 174 · see citing works
Microfluidic bioprinting for organ-on-a-chip models
Yu, F., & Choudhury, D. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.03.025 · Cited by 161 · see citing works
The Phenion® Full-Thickness Skin Model for Percutaneous Absorption Testing
Ackermann, K., Borgia, S. L., Korting, H. C., et al. (2009) · Skin Pharmacology and Physiology · doi:10.1159/000265681 · Cited by 151 · see citing works
Zhuang, P., Ng, W. L., An, J., Chua, C. K., & Tan, L. P. (2019) · PLoS ONE · doi:10.1371/journal.pone.0216776 · Cited by 142 · see citing works
Self-citationResolution and shape in bioprinting: Strategizing towards complex tissue and organ printing
Lee, J. M., Ng, W. L., & Yeong, W. Y. (2019) · Applied Physics Reviews · doi:10.1063/1.5053909 · Cited by 138 · see citing works
Self-citationKoch, L., Deiwick, A., Franke, A., Schwanke, K., Haverich, A., Zweigerdt, R., & Chichkov, B. N. (2018) · Biofabrication · doi:10.1088/1758-5090/aab981 · Cited by 132 · see citing works
Simulations of 3D bioprinting: predicting bioprintability of nanofibrillar inks
Göhl, J., Markstedt, K., Mark, A., Håkansson, K. M. O., Gatenholm, P., & Edelvik, F. (2018) · Biofabrication · doi:10.1088/1758-5090/aac872 · Cited by 132 · see citing works
Ng, W. L., Yeong, W. Y., & Naing, M. W. (2017) · Materials · doi:10.3390/ma10020190 · Cited by 127 · see citing works
Self-citationDerr, K., Zou, J., Luo, K., Song, M. J., Sittampalam, G. S., Zhou, C., Michael, S., Ferrer, M., & Derr, P. (2019) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2018.0318 · Cited by 120 · see citing works
van den Broek, L. J., Bergers, L. L., Reijnders, C. M. A., & Gibbs, S. (2017) · Stem Cell Reviews and Reports · doi:10.1007/s12015-017-9737-1 · Cited by 116 · see citing works
Healing of Chronic Wounds: An Update of Recent Developments and Future Possibilities
Kathawala, M. H., Ng, W. L., Liu, D., Naing, M. W., Yeong, W. Y., Spiller, K. L., Dyke, M. E. V., & Ng, K. W. (2019) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2019.0019 · Cited by 114 · see citing works
Self-citationNg, W. L., Goh, M. H., Yeong, W. Y., & Naing, M. W. (2018) · Biomaterials Science · doi:10.1039/c7bm01015j · Cited by 111 · see citing works
Self-citationBarata, D., van Blitterswijk, C. V., & Habibović, P. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.09.009 · Cited by 107 · see citing works
A Toxicology for the 21st Century—Mapping the Road Ahead
Härtung, T. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp059 · Cited by 105 · see citing works
Development of Polyelectrolyte Chitosan-gelatin Hydrogels for Skin Bioprinting
Ng, W. L., Yeong, W. Y., & Naing, M. W. (2016) · Procedia CIRP · doi:10.1016/j.procir.2015.09.002 · Cited by 103 · see citing works
Self-citationDrug Discovery Goes Three-Dimensional: Goodbye to Flat High-Throughput Screening?
Eglen, R. M., & Randle, D. H. (2015) · Assay and Drug Development Technologies · doi:10.1089/adt.2015.647 · Cited by 78 · see citing works
Multi-chamber microfluidic platform for high-precision skin permeation testing
Alberti, M., Dancik, Y., Sriram, G., Wu, B., Teo, Y. L., Feng, Z., Bigliardi‐Qi, M., Wu, R., Wang, Z. P., & Bigliardi, P. L. (2017) · Lab on a Chip · doi:10.1039/c6lc01574c · Cited by 73 · see citing works
Characterizing the effects of cell settling on bioprinter output
Pepper, M. E., Seshadri, V., Burg, T. C., et al. (2012) · Biofabrication · doi:10.1088/1758-5082/4/1/011001 · Cited by 59 · see citing works
Burden, N., Sewell, F. R., & Chapman, K. L. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002156 · Cited by 53 · see citing works
An Alternative Direct Compound Dispensing Method Using the HP D300 Digital Dispenser
Jones, R. E., Zheng, W., McKew, J. C., et al. (2013) · SLAS TECHNOLOGY · doi:10.1177/2211068213491094 · Cited by 32 · see citing works
Bouhifd, M., Bories, G., Casado, J., et al. (2012) · Food and Chemical Toxicology · doi:10.1016/j.fct.2012.03.046 · Cited by 30 · see citing works
Human Skin Equivalents Demonstrate Need for Neuro‐Immuno‐Cutaneous System
Yucha, S. E. V., Tamamoto, K. A., Nguyen, H., Cairns, D. M., & Kaplan, D. L. (2018) · Advanced Biosystems · doi:10.1002/adbi.201800283 · Cited by 28 · see citing works
Test No. 439: In Vitro Skin Irritation - Reconstructed Human Epidermis Test Method
OECD (2013) · OECD eBooks · doi:10.1787/9789264203884-en · Cited by 28 · see citing works
Potential of Bioprinted Films for Skin Tissue Engineering
Ng, W. L., Yeong, W. Y., & Naing, M. W. (2014) · doi:10.3850/978-981-09-0446-3_065 · Cited by 27 · see citing works
Self-citationMicrovalve bioprinting of cellular droplets with high resolution and consistency
Ng, W. L., Yeong, W. Y., & Naing, M. W. (2016) · DR-NTU (Nanyang Technological University) · Cited by 15 · see citing works
Self-citationNg, W. L., Wang, S., Yeong, W. Y., et al. (2016) · Trends in biotechnology · doi:10.1016/j.tibtech.2016.08.009 · Cited by 9 · see citing works
Self-citationTest No. 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis (Rhe) Test Method
OECD (2014) · OECD eBooks · doi:10.1787/9789264224193-en · Cited by 4 · see citing works
Rapid tooling and manufacturing
(2013) · CRC Press eBooks · doi:10.1201/b15961-59 · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [27]Chua CK Yeong WY Leong KF 2005Rapid Prototyping in Tissue Engineering:A State-of-the-Art Report Proceeding 2nd International Conference on Advanced Research in Virtual and Rapid Prototyping 19 27
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Alnuqaydan, A. M. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1439027 · Cited by 84 · see citing works
“The model accurately predicted skin compatibility, reducing the need for animal testing and providing more reliable safety assessments (137).”
In vitro 3D skin culture and its sustainability in toxicology: a narrative review
Masri, S., Fauzi, M. B., Rajab, N. F., Lee, W.-H., Zainal Abidin, D. A., & Siew, E. L. (2024) · Artificial Cells, Nanomedicine, and Biotechnology · doi:10.1080/21691401.2024.2407617 · Cited by 15 · see citing works
- Authors
- Ng, W. L., & Yeong, W. Y.
- Affiliations
- Nanyang Technological University (SG)
- Corresponding author
- Yeong, Wai Yee
- Venue
- International Journal of Bioprinting
- Publisher
- AccScience Publishing
- Published
- 2019-09-20
- Volume
- 5
- Issue
- 1
- Pages
- 237
- ISSN
- 2424-7723 (ISSN-L)
- 2424-8002
- PMC
- PMC7310273
- OpenAlex
- W2974118947
- Cited by
- 48
- References
- 69
- Citations by year
- 2025: 6 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 8 · 2020: 5 · 2019: 1 · 2018: 1
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- International Journal of Bioprinting (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion, cc-by-nc)
- Funders
- Hewlett-Packard Development Company
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- 3D bioprinting, microfluidics, in vitro skin model, chemical safety assessment, high-throughput screening, real-time monitoring
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