Human‐on‐Leaf‐Chip: A Biomimetic Vascular System Integrated with Chamber‐Specific Organs
Open accessAbstract
The vascular network is a central component of the organ‐on‐a‐chip system to build a 3D physiological microenvironment with controlled physical and biochemical variables. Inspired by ubiquitous biological systems such as leaf venation and circulatory systems, a fabrication strategy is devised to develop a biomimetic vascular system integrated with freely designed chambers, which function as niches for chamber‐specific vascularized organs. As a proof of concept, a human‐on‐leaf‐chip system with biomimetic multiscale vasculature systems connecting the self‐assembled 3D vasculatures in chambers is fabricated, mimicking the in vivo complex architectures of the human cardiovascular system connecting vascularized organs. Besides, two types of vascularized organs are built independently within the two halves of the system to verify its feasibility for conducting comparative experiments for organ‐specific metastasis studies in a single chip. Successful culturing of human hepatoma G2 cells (HepG2s) and mesenchymal stem cells (MSCs) with human umbilical vein endothelial cells (HUVECs) shows good vasculature formation, and organ‐specific metastasis is simulated through perfusion of pancreatic cancer cells and shows distinct cancer encapsulation by MSCs, which is absent in HepG2s. Given good culture efficacy, study design flexibility, and ease of modification, these results show that the bioinspired human‐on‐leaf‐chip possesses great potential in comparative and metastasis studies while retaining organ‐to‐organ crosstalk.
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A vascularized MSC microenvironment provided a suitable platform for pancreatic cancer cell growth.
“This vascularized MSC microenvironment provided a suitable platform for pancreatic cancer cell growth.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [217]
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Cites
The Physiological Principle of Minimum Work
Murray, C. D. (1926) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.12.3.207 · Cited by 2,105 · see citing works
3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs
Kolesky, D. B., Truby, R. L., Gladman, A. S., Busbee, T. A., Homan, K. A., & Lewis, J. A. (2014) · Advanced Materials · doi:10.1002/adma.201305506 · Cited by 2,102 · see citing works
Metastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062 · see citing works
In vitro microvessels for the study of angiogenesis and thrombosis
Zheng, Y., Chen, J., Craven, M., Choi, N. W., Totorica, S., Diaz-Santana, A., Kermani, P., Hempstead, B., Fischbach-Teschl, C., López, J. A., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201240109 · Cited by 894 · see citing works
Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function
Zervantonakis, I. K., Hughes-Alford, S. K., Charest, J. L., Condeelis, J. S., Gertler, F. B., & Kamm, R. D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210182109 · Cited by 872 · see citing works
Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment
Huang, G., Li, F., Zhao, X., Ma, Y., Li, Y., Lin, M., Jin, G., Lu, T. J., Genin, G. M., & Xu, F. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00094 · Cited by 825 · see citing works
Self-citationHuman 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation
Jeon, J. S., Bersini, S., Gilardi, M., Dubini, G., Charest, J. L., Moretti, M., & Kamm, R. D. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417115112 · Cited by 723 · see citing works
Zhang, B., Montgomery, M., Chamberlain, M. D., Ogawa, S., Korolj, A., Pahnke, A., Wells, L. A., Massé, S., Kim, J., Reis, L., et al. (2016) · Nature Materials · doi:10.1038/nmat4570 · Cited by 593 · see citing works
Surviving at a Distance: Organ-Specific Metastasis
Obenauf, A. C., & Massagué, J. (2015) · Trends in cancer · doi:10.1016/j.trecan.2015.07.009 · Cited by 569 · see citing works
Creating perfused functional vascular channels using 3D bio-printing technology
Lee, V. K., Kim, D. Y., Ngo, H., Lee, Y., Seo, L., Yoo, S.-S., Vincent, P. A., & Dai, G. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.05.083 · Cited by 494 · see citing works
Water transport in plants obeys Murray's law
McCulloh, K. A., Sperry, J. S., & Adler, F. R. (2003) · Nature · doi:10.1038/nature01444 · Cited by 466 · see citing works
VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma
Beckermann, B. M., Kallifatidis, G., Groth, A., Frommhold, D., Apel, A., Mattern, J., Salnikov, A. V., Moldenhauer, G., Wagner, W., Diehlmann, A., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604508 · Cited by 406 · see citing works
Chen, M. B., Whisler, J. A., Fröse, J., Yu, C., Shin, Y., & Kamm, R. D. (2017) · Nature Protocols · doi:10.1038/nprot.2017.018 · Cited by 385 · see citing works
Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds
Gershlak, J. R., Hernandez, S., Fontana, G., Perreault, L. R., Hansen, K. J., Larson, S. A., Binder, B. Y. K., Dolivo, D. M., Yang, T., Dominko, T., et al. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.02.011 · Cited by 375 · see citing works
Damage and Fluctuations Induce Loops in Optimal Transport Networks
Katifori, E., Szöllősi, G. J., & Magnasco, M. O. (2010) · Physical Review Letters · doi:10.1103/physrevlett.104.048704 · Cited by 361 · see citing works
Microfluidic techniques for development of 3D vascularized tissue
Hasan, A., Paul, A., Vrana, N. E., Zhao, X., Memic, A., Hwang, Y.-S., Dokmeci, M. R., & Khademhosseini, A. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.04.091 · Cited by 282 · see citing works
Self-citationTubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels
Bischel, L. L., Young, E. W. K., Mader, B. R., & Beebe, D. J. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.11.005 · Cited by 266 · see citing works
Fluid shear stress activates YAP1 to promote cancer cell motility
Lee, H. J., Diaz, M. F., Price, K. M., Ozuna, J. A., Zhang, S., Sevick-Muraca, E. M., Hagan, J. P., & Wenzel, P. L. (2017) · Nature Communications · doi:10.1038/ncomms14122 · Cited by 258 · see citing works
Colorectal tumor-on-a-chip system: a 3D tool for precision onco-nanomedicine
Carvalho, M. R., Barata, D., Teixeira, L. M., Giselbrecht, S., Reis, R. L., Oliveira, J. M., Truckenmüller, R., & Habibovic, P. (2019) · Science Advances · doi:10.1126/sciadv.aaw1317 · Cited by 230 · see citing works
Organ-on-chip models of cancer metastasis for future personalized medicine: From chip to the patient
Caballero, D., Kaushik, S., Correlo, V. M., Oliveira, J. M., Reis, R. L., & Kundu, S. C. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.10.005 · Cited by 221 · see citing works
Qiu, Y., Ahn, B., Sakurai, Y., Hansen, C. E., Tran, R., Mimche, P. N., Mannino, R. G., Ciciliano, J. C., Lamb, T. J., Joiner, C. H., et al. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0224-z · Cited by 188 · see citing works
Leaf palmate venation and vascular redundancy confer tolerance of hydraulic disruption
Sack, L., Dietrich, E. M., Streeter, C. M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709333105 · Cited by 164 · see citing works
Flow-driven assembly of VWF fibres and webs in in vitro microvessels
Zheng, Y. Y., Chen, J., & López, J. A. (2015) · Nature Communications · doi:10.1038/ncomms8858 · Cited by 150 · see citing works
Adaptation and Optimization of Biological Transport Networks
Hu, D., & Cai, D. (2013) · Physical Review Letters · doi:10.1103/physrevlett.111.138701 · Cited by 147 · see citing works
Urosevic, J., García‐Albéniz, X., Planet, E., Real, S., Céspedes, M. V., Guiu, M., Fernández, E., Bellmunt, A., Gawrzak, S., Pavlović, M., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb2977 · Cited by 143 · see citing works
Structure, Scaling, and Phase Transition in the Optimal Transport Network
Bohn, S., & Magnasco, M. O. (2007) · Physical Review Letters · doi:10.1103/physrevlett.98.088702 · Cited by 137 · see citing works
Direct-write assembly of biomimetic microvascular networks for efficient fluid transport
Wu, W., Hansen, C. J., Aragón, A. M., Geubelle, P. H., White, S. R., & Lewis, J. A. (2009) · Soft Matter · doi:10.1039/b918436h · Cited by 121 · see citing works
Optimal design of microfluidic networks using biologically inspired principles
Barber, R. W., & Emerson, D. R. (2007) · Microfluidics and Nanofluidics · doi:10.1007/s10404-007-0163-6 · Cited by 116 · see citing works
Fabrication of nature-inspired microfluidic network for perfusable tissue constructs
He, J., Mao, M., Liu, Y., Shao, J., Jin, Z., & Li, D. (2013) · Advanced Healthcare Materials · doi:10.1002/adhm.201200404 · Cited by 76 · see citing works
Self-citationArtificial lymphatic drainage systems for vascularized microfluidic scaffolds
Wong, K. H. K., Truslow, J. G., Khankhel, A. H., Chan, K. L. S., & Tien, J. (2012) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34524 · Cited by 74 · see citing works
Principles of Biomimetic Vascular Network Design Applied to a Tissue-Engineered Liver Scaffold
Hoganson, D. M., Pryor, H. I., Spool, I. D., Burns, O. H., Gilmore, J. R., & Vacanti, J. P. (2009) · Tissue Engineering Part A · doi:10.1089/ten.tea.2009.0118 · Cited by 61 · see citing works
Saïas, L., Autebert, J., Malaquin, L., & Viovy, J. (2011) · Lab on a Chip · doi:10.1039/c0lc00304b · Cited by 59 · see citing works
Plant leaves as templates for soft lithography
Wu, W., Guijt, R. M., Silina, Y. E., Koch, M., & Manz, A. (2016) · RSC Advances · doi:10.1039/c5ra25890a · Cited by 55 · see citing works
Saito, K., Sakaguchi, M., Maruyama, S., et al. (2018) · Journal of Cancer · doi:10.7150/jca.24415 · Cited by 55 · see citing works
Yildirimer, L., Zhang, Q., Kuang, S., Cheung, J. C., Chu, K. A., He, Y., Yang, M., & Zhao, X. (2019) · Biofabrication · doi:10.1088/1758-5090/ab17aa · Cited by 52 · see citing works
Self-citationCharacterization of Leaf-Inspired Microfluidic Chips for Pumpless Fluid Transport
He, J., Mao, M., Li, D., Liu, Y., & Jin, Z. (2014) · Journal of Bionic Engineering · doi:10.1016/s1672-6529(14)60025-1 · Cited by 31 · see citing works
Self-citationLeaf-templated, microwell-integrated microfluidic chips for high-throughput cell experiments
Mao, M., He, J., Lu, Y., Li, X., Li, T., Zhou, W., & Li, D. (2018) · Biofabrication · doi:10.1088/1758-5090/aaa900 · Cited by 29 · see citing works
Self-citationLi, J., Wei, J., Liu, Y., Liu, B., Liu, T., Jiang, Y., Ding, L., & Liu, C. (2017) · Lab on a Chip · doi:10.1039/c7lc00343a · Cited by 24 · see citing works
Miali, M. E., Colasuonno, M., Surdo, S., Palomba, R., Pereira, R. C., Rondanina, E., Diaspro, A., Pascazio, G., & Decuzzi, P. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b09453 · Cited by 17 · see citing works
Flagged first, then by citations
Research works printed but not linked: 10
- Yildirimer, L.; Zhang, Q.; Kuang, S.; Cheung, C.-W. J.; Chu, K. A.; He, Y.; Yang, M.; Zhao, X., Biofabrication 2019, 11 (3), 032003.
- Huang, G.; Li, F.; Zhao, X.; Ma, Y.; Li, Y.; Lin, M.; Jin, G.; Lu, T. J.; Genin, G. M.; Xu, F., Chemical reviews 2017, 117 (20), 12764-12850.
- Hasan, A.; Paul, A.; Vrana, N. E.; Zhao, X.; Memic, A.; Hwang, Y.-S.; Dokmeci, M. R.; Khademhosseini, A., Biomaterials 2014, 35 (26), 7308-7325.
- Kolesky, D. B.; Truby, R. L.; Gladman, A. S.; Busbee, T. A.; Homan, K. A.; Lewis, J. A., Adv. Mater. 2014, 26 (19), 3124.
- Zhang, B.; Montgomery, M.; Chamberlain, M. D.; Ogawa, S.; Korolj, A.; Pahnke, A.; Wells, L. A.; Massé, S.; Kim, J.; Reis, L., Nature Materials 2016, 15 (6), 669.
- McCulloh, K. A.; Sperry, J. S.; Adler, F. R., Nature 2003, 421 (6926), 939-42.
- He, J.; Mao, M.; Liu, Y.; Shao, J.; Jin, Z.; Li, D., Advanced Healthcare Materials 2013, 2 (8), 1108-1113.
- Mao, M.; Jiankang, H.; Yongjie, L.; Xiao, L.; Tianjiao, L.; Wenxing, Z.; Dichen, L., Biofabrication 2018, 10 (2), 025008.
- Gershlak, J. R.; Hernandez, S.; Fontana, G.; Perreault, L. R.; Hansen, K. J.; Larson, S. A.; Binder, B. Y.; Dolivo, D. M.; Yang, T.; Dominko, T., Biomaterials 2017, 125, 13-22.
- He, J.; Mao, M.; Li, D.; Liu, Y.; Jin, Z., 仿生工程学报(英文版) 2014, 11 (1), 109-114.
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Mao, M., Qu, X., Zhang, Y., Gu, B., Li, C., Liu, R., Li, X., Zhu, H., He, J., & Li, D. (2023) · Nature Communications · doi:10.1038/s41467-023-37716-1 · Cited by 42 · see citing works
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- Authors
- Mao, M., Bei, H. P., Lam, C. H., Chen, P., Wang, S., Chen, Y., He, J., & Zhao, X.
- Affiliations
- Hong Kong Polytechnic University (HK)
- Xi'an Jiaotong University (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Guangdong University of Technology (CN)
- Corresponding author
- He, Jiankang
- Zhao, Xin
- Venue
- Small
- Publisher
- Wiley
- Published
- 2020-04-24
- Volume
- 16
- Issue
- 22
- Pages
- e2000546-e2000546
- ISSN
- 1613-6810 (ISSN-L)
- 1613-6829
- OpenAlex
- W3020462440
- Cited by
- 71
- References
- 39
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 11 · 2023: 20 · 2022: 9 · 2021: 13 · 2020: 6
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Small (publishedVersion)
- PubMed (publishedVersion)
- PolyU Institutional Research Archive (Hong Kong Polytechnic University) (submittedVersion)
- Funders
- General Research Fund of Shanghai Normal University (15202119)
- Hong Kong Polytechnic University
- National Natural Science Foundation of China
- Fundamental Research Funds for the Central Universities
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- organ-on-a-chip, leaf venation, organ-specific metastasis, human umbilical vein endothelial cells, mesenchymal stem cells, HepG2 cells, pancreatic cancer, organ perfusion
- MeSH terms
- Humans, Neoplasms, Plant Leaves, Biomimetics, Lab-On-A-Chip Devices, Tumor Microenvironment, Mesenchymal Stem Cells, Human Umbilical Vein Endothelial Cells
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