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The future of skin toxicology testing – 3D bioprinting meets microfluidics

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Wei Long Ng, Wai Yee Yeong

Abstract


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 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.

Keywords


3D Bioprinting; 3D Printing; Additive manufacturing; Microfluidics; Skin bioprinting

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References


T. Hartung, Toxicology for the twenty-first century, Nature 460(7252) (2009) 208-212.

MarketsandMarkets, Global In Vitro Toxicology Testing Market by Product, Type (ADME), Toxicity Endpoints & Tests (Carcinogenicity, Dermal Toxicity), Technology (Genomics, Transcriptomics), Method (Cellular Assays), Industry (Pharmaceutical) - Forecast to 2021, 2016.

W. Lilienblum, W. Dekant, H. Foth, T. Gebel, J. Hengstler, R. Kahl, P.-J. Kramer, H. Schweinfurth, K.-M. Wollin, Alternative methods to safety studies in experimental animals: role in the risk assessment of chemicals under the new European Chemicals Legislation (REACH), Arch. Toxicol. 82(4) (2008) 211-236.

N. Burden, F. Sewell, K. Chapman, Testing chemical safety: what is needed to ensure the widespread application of non-animal approaches?, PLoS Biol. 13(5) (2015) e1002156.

T. Hartung, A toxicology for the 21st century—mapping the road ahead, Toxicol. Sci. 109(1) (2009) 18-23.

S. Vijayavenkataraman, W. Lu, J. Fuh, 3D bioprinting of skin: a state-of-the-art review on modelling, materials, and processes, Biofabrication 8(3) (2016) 032001.

L.J. van den Broek, L.I. Bergers, C.M. Reijnders, S. Gibbs, Progress and future prospectives in skin-on-chip development with emphasis on the use of different cell types and technical challenges, Stem Cell Reviews and Reports 13(3) (2017) 418-429.

G. Du, Q. Fang, J.M. den Toonder, Microfluidics for cell-based high throughput screening platforms—A review, Anal. Chim. Acta 903 (2016) 36-50.

D. Barata, C. van Blitterswijk, P. Habibovic, High-throughput screening approaches and combinatorial development of biomaterials using microfluidics, Acta Biomater. 34 (2016) 1-20.

S. MacNeil, Progress and opportunities for tissue-engineered skin, Nature 445(7130) (2007) 874-880.

S.H. Mathes, H. Ruffner, U. Graf-Hausner, The use of skin models in drug development, Adv. Drug Del. Rev. 69 (2014) 81-102.

W.L. Ng, M.H. Goh, W.Y. Yeong, M.W. Naing, Applying Macromolecular Crowding to 3D Bioprinting: Fabrication of 3D Hierarchical Porous Collagen-based Hydrogel Constructs, Biomater. Sci. 6(3) (2018) 562-574.

W.L. Ng, S. Wang, W.Y. Yeong, M.W. Naing, Skin Bioprinting: Impending Reality or Fantasy? , Trends Biotechnol. 34 (9) (2016) 689 - 699.

OECD, Skin Absorption: In Vitro Method, 2004.

OECD, In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method, 2014.

OECD, In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method, 2013.

OECD, In Vitro Skin Sensitization: ARE-Nrf2 Luciferase Test Method, 2015.

T. Sun, S. Jackson, J.W. Haycock, S. MacNeil, Culture of skin cells in 3D rather than 2D improves their ability to survive exposure to cytotoxic agents, J. Biotechnol. 122(3) (2006) 372-381.

K. Ackermann, S.L. Borgia, H.C. Korting, K. Mewes, M. Schäfer-Korting, The Phenion® full-thickness skin model for percutaneous absorption testing, Skin pharmacology and physiology 23(2) (2010) 105-112.

L. Horváth, Y. Umehara, C. Jud, F. Blank, A. Petri-Fink, B. Rothen-Rutishauser, Engineering an in vitro air-blood barrier by 3D bioprinting, Sci. Rep. 5 (2015) 7974.

J.M. Lee, W.L. Ng, W.Y. Yeong, Resolution and shape in bioprinting: Strategizing towards complex tissue and organ printing, Appl. Phys. Rev 6(1) (2019) 011307.

T. Boland, A. Ovsianikov, B.N. Chickov, A. Doraiswamy, R.J. Narayan, W.Y. Yeong, K.F. Leong, C.K. Chua, Rapid prototyping of artificial tissues and medical devices, Advanced Materials & Processes 165(4) (2007) 51-53.

W.-Y. Yeong, C.-K. Chua, K.-F. Leong, M. Chandrasekaran, M.-W. Lee, Development of scaffolds for tissue engineering using a 3D inkjet, Virtual Modelling and Rapid Manufacturing: Advanced Research in Virtual and Rapid Prototyping Proc. 2nd Int. Conf. on Advanced Research in Virtual and Rapid Prototyping, 28 Sep-1 Oct 2005, Leiria, Portugal, CRC Press, 2005, p. 115.

C.-K. Chua, W.-Y. Yeong, K.-F. Leong, Rapid prototyping in tissue engineering: a state-of-the-art report, Proc. 2nd Int. Conf. on Advanced Research in Virtual and Rapid Prototyping, 2005, pp. 19-27.

J. Groll, J.A. Burdick, D.-W. Cho, B. Derby, M. Gelinsky, S.C. Heilshorn, T. Juengst, J. Malda, V.A. Mironov, K. Nakayama, A definition of bioinks and their distinction from biomaterial inks, Biofabrication 11(1) (2018) 013001.

L.J. Pourchet, A. Thepot, M. Albouy, E.J. Courtial, A. Boher, L.J. Blum, C.A. Marquette, Human skin 3D bioprinting using scaffold‐free approach, Adv Healthc Mater. 6(4) (2017) 1601101.

N. Cubo, M. Garcia, J.F. del Cañizo, D. Velasco, J.L. Jorcano, 3D bioprinting of functional human skin: production and in vivo analysis, Biofabrication 9(1) (2016) 015006.

W.L. Ng, W.Y. Yeong, M.W. Naing, Polyelectrolyte gelatin-chitosan hydrogel optimized for 3D bioprinting in skin tissue engineering, Int J Bioprint 2 (1) (2016) 53-62.

W.L. Ng, W.Y. Yeong, M.W. Naing, Development of Polyelectrolyte Chitosan-gelatin Hydrogels for Skin Bioprinting, Procedia CIRP 49 (2016) 105-112.

L. Koch, A. Deiwick, S. Schlie, S. Michael, M. Gruene, V. Coger, D. Zychlinski, A. Schambach, K. Reimers, P.M. Vogt, Skin tissue generation by laser cell printing, Biotechnol. Bioeng. 109(7) (2012) 1855-1863.

S. Michael, H. Sorg, C.-T. Peck, L. Koch, A. Deiwick, B. Chichkov, P.M. Vogt, K. Reimers, Tissue Engineered Skin Substitutes Created by Laser-Assisted Bioprinting Form Skin-Like Structures in the Dorsal Skin Fold Chamber in Mice, PloS one 8(3) (2013) e57741.

L. Koch, A. Deiwick, A. Franke, K. Schwanke, A. Haverich, R. Zweigerdt, B. Chichkov, Laser bioprinting of human induced pluripotent stem cells—the effect of printing and biomaterials on cell survival, pluripotency, and differentiation, Biofabrication 10(3) (2018) 035005.

W.L. Ng, J.M. Lee, W.Y. Yeong, M. Win Naing, Microvalve-based bioprinting – process, bio-inks and applications, Biomater. Sci. 5(4) (2017) 632-647.

V. Lee, G. Singh, J.P. Trasatti, C. Bjornsson, X. Xu, T.N. Tran, S.-S. Yoo, G. Dai, P. Karande, Design and Fabrication of Human Skin by Three-Dimensional Bioprinting, Tissue Eng Part C: Methods 20(6) (2013) 473-484.

W.L. Ng, W.Y. Yeong, M.W. Naing, Microvalve bioprinting of cellular droplets with high resolution and consistency, Proceedings of the International Conference on Progress in Additive Manufacturing (2016) 397-402.

B.S. Kim, J.-S. Lee, G. Gao, D.-W. Cho, Direct 3D cell-printing of human skin with functional transwell system, Biofabrication 9(2) (2017) 025034.

K. Derr, J. Zou, K. Luo, M.J. Song, G.S. Sittampalam, C. Zhou, S. Michael, M. Ferrer, P. Derr, Fully Three-Dimensional Bioprinted Skin Equivalent Constructs with Validated Morphology and Barrier Function, Tissue Eng Part C: Methods 25(6) (2019) 334-343.

W. Lee, J.C. Debasitis, V.K. Lee, J.-H. Lee, K. Fischer, K. Edminster, J.-K. Park, S.-S. Yoo, Multi-layered culture of human skin fibroblasts and keratinocytes through three-dimensional freeform fabrication, Biomaterials 30(8) (2009) 1587-1595.

W. Lee, V. Lee, S. Polio, P. Keegan, J.H. Lee, K. Fischer, J.K. Park, S.S. Yoo, On-demand three-dimensional freeform fabrication of multi-layered hydrogel scaffold with fluidic channels, Biotechnol. Bioeng. 105(6) (2010) 1178-86.

A. Skardal, D. Mack, E. Kapetanovic, A. Atala, J.D. Jackson, J. Yoo, S. Soker, Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds, Stem cells translational medicine 1(11) (2012) 792-802.

M. Albanna, K.W. Binder, S.V. Murphy, J. Kim, S.A. Qasem, W. Zhao, J. Tan, I.B. El-Amin, D.D. Dice, J. Marco, In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds, Sci. Rep. 9(1) (2019) 1856.

W.L. Ng, Z.Q. Tan, W.Y. Yeong, M.W. Naing, Proof-of-concept: 3D bioprinting of pigmented human skin constructs, Biofabrication 10(2) (2018) 025005.

D. Min, W. Lee, I.H. Bae, T.R. Lee, P. Croce, S.S. Yoo, Bioprinting of biomimetic skin containing melanocytes, Experimental dermatology 27(5) (2018) 453-459.

S.E. Vidal Yucha, K.A. Tamamoto, H. Nguyen, D.M. Cairns, D.L. Kaplan, Human Skin Equivalents Demonstrate Need for Neuro‐Immuno‐Cutaneous System, Advanced Biosystems 3(1) (2019) 1800283.

B.S. Kim, G. Gao, J.Y. Kim, D.W. Cho, 3D Cell Printing of Perfusable Vascularized Human Skin Equivalent Composed of Epidermis, Dermis, and Hypodermis for Better Structural Recapitulation of Native Skin, Adv Healthc Mater. 8(7) (2019) 1801019.

M.E. Pepper, V. Seshadri, T.C. Burg, K.J. Burg, R.E. Groff, Characterizing the effects of cell settling on bioprinter output, Biofabrication 4(1) (2012) 011001.

J. Jia, D.J. Richards, S. Pollard, Y. Tan, J. Rodriguez, R.P. Visconti, T.C. Trusk, M.J. Yost, H. Yao, R.R. Markwald, Engineering alginate as bioink for bioprinting, Acta Biomater. 10(10) (2014) 4323-4331.

P. Zhuang, W.L. Ng, J. An, C.K. Chua, L.P. Tan, Layer-by-layer ultraviolet assisted extrusion-based (UAE) bioprinting of hydrogel constructs with high aspect ratio for soft tissue engineering applications, PLoS One 14(6) (2019) e0216776.

W.L. Ng, W.Y. Yeong, M.W. Naing, Polyvinylpyrrolidone-Based Bio-Ink Improves Cell Viability and Homogeneity during Drop-On-Demand Printing, Materials 10(2) (2017) 190.

M. Bouhifd, G. Bories, J. Casado, S. Coecke, H. Norlén, N. Parissis, R.M. Rodrigues, M.P. Whelan, Automation of an in vitro cytotoxicity assay used to estimate starting doses in acute oral systemic toxicity tests, Food Chem. Toxicol. 50(6) (2012) 2084-2096.

R.E. Jones, W. Zheng, J.C. McKew, C.Z. Chen, An alternative direct compound dispensing method using the HP D300 digital dispenser, Journal of laboratory automation 18(5) (2013) 367-374.

K. Ronaldson-Bouchard, G. Vunjak-Novakovic, Organs-on-a-chip: a fast track for engineered human tissues in drug development, Cell Stem Cell 22(3) (2018) 310-324.

F. Yu, D. Choudhury, Microfluidic bioprinting for organ-on-a-chip models, Drug Discovery Today 24 (6) (2019) 1248 - 1257.

T.H. Park, M.L. Shuler, Integration of cell culture and microfabrication technology, Biotechnol. Progr. 19(2) (2003) 243-253.

T. Thorsen, S.J. Maerkl, S.R. Quake, Microfluidic large-scale integration, Science 298(5593) (2002) 580-584.

W.H. Grover, R.H. Ivester, E.C. Jensen, R.A. Mathies, Development and multiplexed control of latching pneumatic valves using microfluidic logical structures, Lab Chip 6(5) (2006) 623-631.

B. Mosadegh, C.-H. Kuo, Y.-C. Tung, Y.-s. Torisawa, T. Bersano-Begey, H. Tavana, S. Takayama, Integrated elastomeric components for autonomous regulation of sequential and oscillatory flow switching in microfluidic devices, Nature physics 6(6) (2010) 433.

H.E. Abaci, K. Gledhill, Z. Guo, A.M. Christiano, M.L. Shuler, Pumpless microfluidic platform for drug testing on human skin equivalents, Lab Chip 15(3) (2015) 882-888.

G. Sriram, M. Alberti, Y. Dancik, B. Wu, R. Wu, Z. Feng, S. Ramasamy, P.L. Bigliardi, M. Bigliardi-Qi, Z. Wang, Full-thickness human skin-on-chip with enhanced epidermal morphogenesis and barrier function, Mater. Today 21(4) (2018) 326-340.

M. Alberti, Y. Dancik, G. Sriram, B. Wu, Y. Teo, Z. Feng, M. Bigliardi-Qi, R. Wu, Z. Wang, P. Bigliardi, Multi-chamber microfluidic platform for high-precision skin permeation testing, Lab Chip 17(9) (2017) 1625-1634.

D. Huh, G.A. Hamilton, D.E. Ingber, From 3D cell culture to organs-on-chips, Trends Cell Biol. 21(12) (2011) 745-754.

S. Breslin, L. O’Driscoll, Three-dimensional cell culture: the missing link in drug discovery, Drug Discovery Today 18(5-6) (2013) 240-249.

M.W. Laschke, M.D. Menger, Life is 3D: Boosting Spheroid Function for Tissue Engineering., Trends Biotechnol. 35 (2017) 133-144.

D. Choudhury, S. Anand, M.W. Naing, The arrival of commercial bioprinters–Towards 3D bioprinting revolution, Int J Bioprint 4(2) (2018) 139.

J. Göhl, K. Markstedt, A. Mark, K.M. Håkansson, P. Gatenholm, F. Edelvik, Simulations of 3D bioprinting: predicting bioprintability of nanofibrillar inks, Biofabrication 10 (3) (2018) 034105.

K. Hölzl, S. Lin, L. Tytgat, S. Van Vlierberghe, L. Gu, A. Ovsianikov, Bioink properties before, during and after 3D bioprinting, Biofabrication 8(3) (2016) 032002.

D. Choudhury, H.W. Tun, T. Wang, M.W. Naing, Organ-derived decellularized extracellular matrix: a game changer for bioink manufacturing?, Trends Biotechnol. 36(8) (2018) 787-805.

P.S. Gungor-Ozkerim, I. Inci, Y.S. Zhang, A. Khademhosseini, M.R. Dokmeci, Bioinks for 3D bioprinting: an overview, Biomater. Sci. 6 (5) (2018) 915-946.

R.M. Eglen, D.H. Randle, Drug discovery goes three-dimensional: goodbye to flat high-throughput screening?, Assay Drug Dev. Technol. 13(5) (2015) 262-265.

A. Mazzocchi, S. Soker, A. Skardal, 3D bioprinting for high-throughput screening: Drug screening, disease modeling, and precision medicine applications, Appl. Phys. Rev 6(1) (2019) 011302.




DOI: http://dx.doi.org/10.18063/ijb.v5i2.1.237

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