Development of 3D Bio printed Tissue Models for Testing Drug Efficacy in Liver Diseases
DOI:
https://doi.org/10.63682/jns.v14i7.5595Keywords:
Extracellular matrix, Cytochrome P450, Tissue Engineering, Personalized Medicine, Drug efficacy and Hepatotoxicity, Liver tissue models, BioprintingAbstract
The liver diseases of public health importance include hepatitis, cirrhosis, and liver cancer and there is a need to develop drugs for these diseases and evaluate them. The current models such as the 2D cell cultures and animal models do not mimic the functionality of human liver tissue, hence high drug failure rates and safety concerns. This paper will therefore aim to discuss the innovations of 3D bio-printed liver tissue models as new technologies in drug effects, safety, and metabolism. The goal here is to do away with the demerits of conventional testing and get more data on human liver performance. Liver tissue organ-on-a-chip models were developed using hepatocytes, endothelial cells, and stellate cells in a biomatrix through 3D bioprinting. The tissues generated through bioprinting were tested for their mechanical strength, electrical conductivity, and for their ability to metabolize drugs. The liver models developed through 3D bioprinting were described to possess structural and functional properties of normal liver tissue. Other cellular functions including albumin synthesis and cytochrome P450 enzyme activity also improved when compared with the 2D culture system. The models showed an enhanced ability to forecast hepatotoxicity and drug metabolism; thus, the applicability of these models in drug discovery and development was confirmed. Three-dimensional bioprinted liver tissue models are more physiological than two-dimensional cell cultures and hence more effective in drug testing. They provide a better understanding of how drugs operate and how deadly they are and might help in changing the concept of animal models and in the development of the idea of personalized medicine. More studies should be directed towards the difficulties linked with vascularization and the stability of the model for it to be used to its maximum potential.
Downloads
Metrics
References
Aavani, F., Biazar, E., Kheilnezhad, B., & Amjad, F. (2022). 3D bio-printing for skin tissue regeneration: Hopes and hurdles. Current Stem Cell Research & Therapy, 17(5), 415-439.
Addissouky, T. A., Sayed, I. E. T. E., Ali, M. M., Wang, Y., Baz, A. E., Khalil, A. A., & Elarabany, N. (2024). Latest advances in hepatocellular carcinoma management and prevention through advanced technologies. Egyptian Liver Journal, 14(1), 2.
Agarwal, T., Banerjee, D., Konwarh, R., Esworthy, T., Kumari, J., Onesto, V., ... & Ozbolat, I. T. (2021). Recent advances in bioprinting technologies for engineering hepatic tissue. Materials Science and Engineering: C, 123, 112013.
Asrani, S. K., Devarbhavi, H., Eaton, J., & Kamath, P. S. (2019). Burden of liver diseases in the world. Journal of hepatology, 70(1), 151-171.
Boon, R., Kumar, M., Tricot, T., Elia, I., Ordovas, L., Jacobs, F., ... & Verfaillie, C. M. (2020). Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines. Nature communications, 11(1), 1393.
Camp, J. G., Sekine, K., Gerber, T., Loeffler-Wirth, H., Binder, H., Gac, M., ... & Treutlein, B. (2017). Multilineage communication regulates human liver bud development from pluripotency. Nature, 546(7659), 533-538.
Colley, H. E., Hearnden, V., Jones, A. V., Weinreb, P. H., Violette, S. M., Macneil, S., ... & Murdoch, C. (2011). Development of tissue-engineered models of oral dysplasia and early invasive oral squamous cell carcinoma. British journal of cancer, 105(10), 1582-1592.
Daly, A. C., Riley, L., Segura, T., & Burdick, J. A. (2020). Hydrogel microparticles for biomedical applications. Nature Reviews Materials, 5(1), 20-43.
Dash, A., Inman, W., Hoffmaster, K., Sevidal, S., Kelly, J., Obach, R. S., ... & Tannenbaum, S. R. (2009). Liver tissue engineering in the evaluation of drug safety. Expert opinion on drug metabolism & toxicology, 5(10), 1159-1174.
Fatimi, A., Okoro, O. V., Podstawczyk, D., Siminska-Stanny, J., & Shavandi, A. (2022). Natural hydrogel-based bio-inks for 3D bioprinting in tissue engineering: a review. Gels, 8(3), 179.
Gu, B. K., Choi, D. J., Park, S. J., Kim, Y. J., & Kim, C. H. (2018). 3D bioprinting technologies for tissue engineering applications. Cutting-edge enabling technologies for regenerative medicine, 15-28.
Järvinen, E., Hammer, H. S., Pötz, O., Ingelman‐Sundberg, M., & Stage, T. B. (2023). 3D spheroid primary human hepatocytes for prediction of cytochrome P450 and drug transporter induction. Clinical Pharmacology & Therapeutics, 113(6), 1284-1294.
Joshi, A., Choudhury, S., Gugulothu, S. B., Visweswariah, S. S., & Chatterjee, K. (2022). Strategies to promote vascularization in 3D printed tissue scaffolds: trends and challenges. Biomacromolecules, 23(7), 2730-2751.
Kaliyaperumal, K., Grove, J. I., Delahay, R. M., Griffiths, W. J., Duckworth, A., & Aithal, G. P. (2018). Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications. Journal of hepatology, 69(4), 948-957.
Kasturi, M., Mathur, V., Gadre, M., Srinivasan, V., & Vasanthan, K. S. (2024). Three dimensional bioprinting for hepatic tissue engineering: from in vitro models to clinical applications. Tissue Engineering and Regenerative Medicine, 21(1), 21-52.
Lee, H., Han, W., Kim, H., Ha, D. H., Jang, J., Kim, B. S., & Cho, D. W. (2017). Development of liver decellularized extracellular matrix bioink for three-dimensional cell printing-based liver tissue engineering. Biomacromolecules, 18(4), 1229-1237.
Li, W., Liu, Z., Tang, F., Jiang, H., Zhou, Z., Hao, X., & Zhang, J. M. (2023). Application of 3D bioprinting in liver diseases. Micromachines, 14(8), 1648.
Lin, C. L., & Kao, J. H. (2018). the prevention of hepatitis B‐related hepatocellular carcinoma. Alimentary Pharmacology & Therapeutics, 48(1), 5-14.
Lu, S., Zhang, J., Lin, S., Zheng, D., Shen, Y., Qin, J., ... & Wang, S. (2021). Recent advances in the development of in vitro liver models for hepatotoxicity testing. Bio-Design and Manufacturing, 4, 717-734.
Ma, X., Qu, X., Zhu, W., Li, Y. S., Yuan, S., Zhang, H., ... & Chen, S. (2016). Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proceedings of the National Academy of Sciences, 113(8), 2206-2211.
Madurska, M. J., Poyade, M., Eason, D., Rea, P., & Watson, A. J. (2017). Development of a patient-specific 3D-printed liver model for preoperative planning. Surgical innovation, 24(2), 145-150.
Mandrycky, C., Wang, Z., Kim, K., & Kim, D. H. (2016). 3D bioprinting for engineering complex tissues. Biotechnology advances, 34(4), 422-434.
Mazzocchi, A., Soker, S., & Skardal, A. (2019). 3D bioprinting for high-throughput screening: Drug screening, disease modeling, and precision medicine applications. Applied Physics Reviews, 6(1).
Murphy, S. V., & Atala, A. (2014). 3D bioprinting of tissues and organs. Nature biotechnology, 32(8), 773-785.
Nie, J., Gao, Q., Fu, J., & He, Y. (2020). Grafting of 3D bioprinting to in vitro drug screening: a review. Advanced healthcare materials, 9(7), 1901773.
Pekor, C., Gerlach, J. C., Nettleship, I., & Schmelzer, E. (2015). Induction of hepatic and endothelial differentiation by perfusion in a three-dimensional cell culture model of human fetal liver. Tissue Engineering Part C: Methods, 21(7), 705-715.
Ramesh, S., Harrysson, O. L., Rao, P. K., Tamayol, A., Cormier, D. R., Zhang, Y., & Rivero, I. V. (2021). Extrusion bioprinting: Recent progress, challenges, and future opportunities. Bioprinting, 21, e00116.
Ramiah, P., Du Toit, L. C., Choonara, Y. E., Kondiah, P. P., & Pillay, V. (2020). Hydrogel-based bioinks for 3D bioprinting in tissue regeneration. Frontiers in Materials, 7, 76.
Schuppan, D., & Afdhal, N. H. (2008). Liver cirrhosis. The Lancet, 371(9615), 838-851.
Serras, A. S., Rodrigues, J. S., Cipriano, M., Rodrigues, A. V., Oliveira, N. G., & Miranda, J. P. (2021). A critical perspective on 3D liver models for drug metabolism and toxicology studies. Frontiers in cell and developmental biology, 9, 626805.
Skardal, A., Murphy, S. V., Devarasetty, M., Mead, I., Kang, H. W., Seol, Y. J., ... & Atala, A. (2017). Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Scientific reports, 7(1), 8837.
van Grunsven, L. A. (2017). 3D in vitro models of liver fibrosis. Advanced drug delivery reviews, 121, 133-146.
Van Norman, G. A. (2020). Limitations of animal studies for predicting toxicity in clinical trials: Part 2: Potential alternatives to the use of animals in preclinical trials. Basic to Translational Science, 5(4), 387-397.
Vijayavenkataraman, S., Yan, W. C., Lu, W. F., Wang, C. H., & Fuh, J. Y. H. (2018). 3D bioprinting of tissues and organs for regenerative medicine. Advanced drug delivery reviews, 132, 296-332.
Wang, D., Maharjan, S., Kuang, X., Wang, Z., Mille, L. S., Tao, M., ... & Zhang, Y. S. (2022). Microfluidic bioprinting of tough hydrogel-based vascular conduits for functional blood vessels. Science Advances, 8(43), eabq6900.
Xiang, Y., Miller, K., Guan, J., Kiratitanaporn, W., Tang, M., & Chen, S. (2022). 3D bioprinting of complex tissues in vitro: state-of-the-art and future perspectives. Archives of toxicology, 96(3), 691-710.
Zhang, L. G., Leong, K., & Fisher, J. P. (Eds.). (2022). 3D bioprinting and nanotechnology in tissue engineering and regenerative medicine. academic press.
Zhong, C., & Xu, H. (2023). Advances in the construction of in vitro liver tissue models using 3D bioprinting technology. Hepatobiliary Surgery and Nutrition, 12(5), 806.
Zhu, W., Ma, X., Gou, M., Mei, D., Zhang, K., & Chen, S. (2016). 3D printing of functional biomaterials for tissue engineering. Current opinion in biotechnology, 40, 103-112.
Downloads
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.