Biomimetic Model of Tumor Microenvironment on Microfluidic Platform
Abstract
The “Tumor microenvironment” (TME) is a complex, interacting system of the tumor and its surrounding environment. The TME has drawn more attention recently in attempts to overcome current drug resistance and the recurrence of cancer by understanding the cancer and its microenvironment systematically, beyond past reductionist approaches. However, a lack of experimental tools to dissect the intricate interactions has hampered in‐depth research into the TME. Here, a biomimetic TME model using a microfluidic platform is presented, which enables the interaction between TME constituents to be studied in a comprehensive manner. Paracrine interactions of cocultured tumor cell lines (SK‐OV‐3, MKN‐74, and SW620) with primary fibroblasts show marked morphological changes in the tumor cells, depending on the type of tumor cells, and, importantly, the composition of the extracellular matrix. Furthermore, this model allows direct observation of angiogenesis induced by the tumor–stroma interaction. Finally, reconstituting simultaneous angiogenesis and lymphangiogenesis induced by the tumor‐stromal interaction with TME mimicking extrinsic factors is enabled. It is believed that the in vitro biomimetic model and the experimental concepts described will help to shed light on the complex biology of the TME.
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Conventional 2D cell monolayers and 3D cell culture models are unable to recapitulate the complex biochemical and biophysical factors of the tumor microenvironment in vivo because they lack the systemic nature of tumors, leading to weak predictive ability.
“2D cell monolayers and three-dimensional cell culture models have been widely employed as initial screening models to provide a cost-efficient and simplified method to elucidate the mechanism of cancer biology or identify the efficacy and safety of a drug candidate14–16; however, they are unable to recapitulate complex biochemical and biophysical factors of the tumor microenvironment (TME) in vivo”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [23]
Cites
Siegel, R. L., Miller, K. D., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21254 · Cited by 11,854 · see citing works
Tumor angiogenesis: therapeutic implications
Sherwood, L. M., Parris, E. E., & Folkman, J. (1971) · New England Journal of Medicine · doi:10.1056/nejm197111182852108 · Cited by 10,187 · see citing works
Molecular mechanisms and clinical applications of angiogenesis
Carmeliet, P., & Jain, R. K. (2011) · Nature · doi:10.1038/nature10144 · Cited by 5,467 · see citing works
Kalluri, R., & Zeisberg, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1877 · Cited by 4,538 · see citing works
Tensional homeostasis and the malignant phenotype
Paszek, M. J., Zahir, N., Johnson, K. R., Lakins, J. N., Rozenberg, G. I., Gefen, A., Reinhart-King, C. A., Margulies, S. S., Dembo, M., Boettiger, D., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.08.010 · Cited by 3,941 · see citing works
Transplacental Carcinogenesis by Stilbestrol
Folkman, J. (1971) · New England Journal of Medicine · doi:10.1056/nejm197108122850711 · Cited by 2,640 · see citing works
The tumor microenvironment and its role in promoting tumor growth
Whiteside, T. L. (2008) · Oncogene · doi:10.1038/onc.2008.271 · Cited by 2,376 · see citing works
Tumor angiogenesis: molecular pathways and therapeutic targets
Weis, S. M., & Cheresh, D. A. (2011) · Nature Medicine · doi:10.1038/nm.2537 · Cited by 1,739 · 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
Engineering of functional, perfusable 3D microvascular networks on a chip
Kim, S., Lee, H., Chung, M., & Jeon, N. L. (2013) · Lab on a Chip · doi:10.1039/c3lc41320a · Cited by 872 · see citing works
Self-citationKojima, Y., Acar, A., Eaton, E. N., Mellody, K. T., Scheel, C., Ben‐Porath, I., Önder, T. T., Wang, Z. C., Richardson, A. L., Weinberg, R. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013805107 · Cited by 851 · see citing works
Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators
Kadler, K. E., Hill, A., & Canty‐Laird, E. G. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.06.008 · Cited by 757 · see citing works
Targeting the tumour vasculature: insights from physiological angiogenesis
Chung, A. S., Lee, J., & Ferrara, N. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2868 · Cited by 751 · see citing works
Tumor microvasculature and microenvironment: Targets for anti-angiogenesis and normalization
Fukumura, D., & Jain, R. K. (2007) · Microvascular Research · doi:10.1016/j.mvr.2007.05.003 · Cited by 699 · see citing works
Loessner, D., Stok, K. S., Lutolf, M. P., Hutmacher, D. W., Clements, J. A., & Rizzi, S. C. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.07.064 · Cited by 602 · see citing works
Interstitial flow influences direction of tumor cell migration through competing mechanisms
Polacheck, W. J., Charest, J. L., & Kamm, R. D. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103581108 · Cited by 509 · see citing works
Activation of fibroblasts in cancer stroma
Räsänen, K., & Vaheri, A. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.04.032 · Cited by 499 · see citing works
Newman, A. C., Nakatsu, M. N., Chou, W., Gershon, P. D., & Hughes, C. C. W. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-05-0393 · Cited by 492 · see citing works
Soft fibrin gels promote selection and growth of tumorigenic cells
Liu, J., Tan, Y., Zhang, H., Zhang, Y., Xu, P., Chen, J., Poh, Y., Tang, K., Wang, N., & Huang, B. (2012) · Nature Materials · doi:10.1038/nmat3361 · Cited by 469 · see citing works
Three-dimensional in vitro tumor models for cancer research and drug evaluation
Xu, X., Farach‐Carson, M. C., & Jia, X. (2014) · Biotechnology Advances · doi:10.1016/j.biotechadv.2014.07.009 · Cited by 462 · see citing works
Yeung, T.-L., Leung, C. S., Wong, K., Samimi, G., Thompson, M. S., Liu, J., Zaid, T. M., Ghosh, S., Birrer, M. J., & Mok, S. C. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0023 · Cited by 394 · see citing works
Chen, L., Xiao, Z., Meng, Y., Zhao, Y., Han, J., Su, G., Chen, B., & Dai, J. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.10.056 · Cited by 292 · see citing works
The evolution of the cancer niche during multistage carcinogenesis
Barcellos‐Hoff, M. H., Lyden, D. C., & Wang, T. C. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3536 · Cited by 275 · see citing works
Rao, R. R., Peterson, A. W., Ceccarelli, J., Putnam, A. J., & Stegemann, J. P. (2012) · Angiogenesis · doi:10.1007/s10456-012-9257-1 · Cited by 260 · see citing works
In vitro model of tumor cell extravasation
Jeon, J. S., Zervantonakis, I. K., Chung, S., Kamm, R. D., & Charest, J. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056910 · Cited by 233 · see citing works
Kim, S., Chung, M., Ahn, J., Lee, S., & Jeon, N. L. (2016) · Lab on a Chip · doi:10.1039/c6lc00910g · Cited by 227 · see citing works
Self-citationTumor cell migration in complex microenvironments
Polacheck, W. J., Zervantonakis, I. K., & Kamm, R. D. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1115-1 · Cited by 222 · see citing works
A three-dimensional in vitro model of tumor cell intravasation
Ehsan, S. M., Welch-Reardon, K. M., Waterman, M. L., Hughes, C. C. W., & George, S. C. (2014) · Integrative Biology · doi:10.1039/c3ib40170g · Cited by 196 · see citing works
Three-dimensional biomimetic model to reconstitute sprouting lymphangiogenesis in vitro
Kim, S., Chung, M., & Jeon, N. L. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2015.11.019 · Cited by 157 · see citing works
Self-citationYoung, E. W. K. (2013) · Integrative Biology · doi:10.1039/c3ib40076j · Cited by 144 · see citing works
Ahmed, N., Riley, C. B., Rice, G. E., & Quinn, M. A. (2005) · Clinical & Experimental Metastasis · doi:10.1007/s10585-005-1262-y · Cited by 140 · see citing works
Wang, J. H., Manning, B. J., Wu, Q. D., Blankson, S., Bouchier‐Hayes, D., & Redmond, H. P. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.2.795 · Cited by 138 · see citing works
Correa de Sampaio, P., Auslaender, D., Krubasik, D., Failla, A. V., Skepper, J. N., Murphy, G., & English, W. R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030753 · Cited by 127 · see citing works
Zins, K., Abraham, D., Sioud, M., & Aharinejad, S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2295 · Cited by 127 · see citing works
Cancer stromal targeting (CAST) therapy
Matsumura, Y. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.12.010 · Cited by 112 · see citing works
Gioiella, F., Urciuolo, F., Imparato, G., Brancato, V., & Netti, P. A. (2016) · Advanced Healthcare Materials · doi:10.1002/adhm.201600772 · Cited by 112 · see citing works
A bioengineered array of 3D microvessels for vascular permeability assay
Lee, H., Kim, S., Chung, M., Kim, J. H., & Jeon, N. L. (2013) · Microvascular Research · doi:10.1016/j.mvr.2013.12.001 · Cited by 88 · see citing works
Self-citationMayer, B., Klement, G. L., Kaneko, M., Man, S., Jothy, S., Rak, J. W., & Kerbel, R. S. (2001) · Gastroenterology · doi:10.1053/gast.2001.27989 · Cited by 76 · see citing works
Colorectal cancer-derived microvesicles modulate differentiation of human monocytes to macrophages
Baj‐Krzyworzeka, M., Mytar, B., Szatanek, R., Surmiak, M., Węglarczyk, K., Baran, J., & Siedlar, M. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-0789-9 · Cited by 59 · see citing works
Newman, A. C., Chou, W., Welch, K. M., Fong, A. H., Popson, S. A., Phan, D. T. T., Sandoval, D. R., Nguyen, D., Gershon, P. D., & Hughes, C. C. W. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.300782 · Cited by 51 · see citing works
Biomimetic tumor microenvironment on a microfluidic platform
Ma, H., Xu, H. M., & Qin, J. (2013) · Biomicrofluidics · doi:10.1063/1.4774070 · Cited by 46 · see citing works
Li, X., Ye, F., Chen, H., Lü, W., Wan, X., & Xie, X. (2007) · Cancer Letters · doi:10.1016/j.canlet.2007.01.024 · Cited by 45 · see citing works
Microvasculature: An essential component for organ-on-chip systems
Lee, H., Chung, M., & Jeon, N. L. (2014) · MRS Bulletin · doi:10.1557/mrs.2013.286 · Cited by 39 · see citing works
Self-citationMatrix identity and tractional forces influence indirect cardiac reprogramming
Kong, Y. P., Carrion, B., Singh, R. K., & Putnam, A. J. (2013) · Scientific Reports · doi:10.1038/srep03474 · Cited by 35 · see citing works
DeWitt, N. D. (2005) · Nature · doi:10.1038/438931a · Cited by 17 · see citing works
Channeling chip power: Tissue chips are being put to the test by industry
Willyard, C. (2017) · Nature Medicine · doi:10.1038/nm0217-138 · Cited by 15 · see citing works
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Vascularized cancer on a chip: the effect of perfusion on growth and drug delivery of tumor spheroid
Nashimoto, Y., Okada, R., Hanada, S., Arima, Y., Nishiyama, K., Miura, T., & Yokokawa, R. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2019.119547 · Cited by 332 · see citing works
Recent Advances in Body-on-a-Chip Systems
Sung, J. H., Wang, Y. I., Narasimhan Sriram, N., Jackson, M., Long, C., Hickman, J. J., & Shuler, M. L. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b05293 · Cited by 258 · see citing works
Organ-on-a-chip meets artificial intelligence in drug evaluation
Deng, S., Li, C., Cao, J., Cui, Z., Du, J., Fu, Z. H., Yang, H., & Chen, P. (2023) · Theranostics · doi:10.7150/thno.87266 · Cited by 272 · see citing works
Tumor-on-a-chip: from bioinspired design to biomedical application
Liu, X., Fang, J., Huang, S., Wu, X., Xie, X., Wang, J., Liu, F., Zhang, M., Peng, Z., & Hu, N. (2021) · Microsystems & Nanoengineering · doi:10.1038/s41378-021-00277-8 · Cited by 246 · see citing works
Microfluidics in nanoparticle drug delivery; From synthesis to pre-clinical screening
Ahn, J., Ko, J., Lee, S., Yu, J., Kim, Y., & Jeon, N. L. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.04.001 · Cited by 213 · see citing works
Self-citationKo, J., Ahn, J., Kim, S., Lee, Y., Lee, J., Park, D., & Jeon, N. L. (2019) · Lab on a Chip · doi:10.1039/c9lc00140a · Cited by 208 · see citing works
Self-citationA Tumor‐on‐a‐Chip System with Bioprinted Blood and Lymphatic Vessel Pair
Cao, X., Ashfaq, R., Cheng, F., Maharjan, S., Li, ., Ying, G., Hassan, S., Xiao, H., Yue, K., & Zhang, Y. S. (2019) · Advanced Functional Materials · doi:10.1002/adfm.201807173 · Cited by 199 · see citing works
Organs-on-chips technologies – A guide from disease models to opportunities for drug development
Monteduro, A. G., Rizzato, S., Caragnano, G., Trapani, A., Giannelli, G., & Maruccio, G. (2023) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115271 · Cited by 185 · see citing works
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Proietto, M., Crippa, M., Damiani, C., Pasquale, V., Sacco, E., Vanoni, M., & Gilardi, M. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1164535 · Cited by 180 · see citing works
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Review on the Vascularization of Organoids and Organoids-on-a-Chip
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Piccolo, N. D., Shirure, V. S., Bi, Y., Goedegebuure, S. P., Gholami, S., Hughes, C. C. W., Fields, R. C., & George, S. C. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.05.008 · Cited by 130 · see citing works
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Self-citationMicrofluidics within a well: an injection-molded plastic array 3D culture platform
Lee, Y., Choi, J. W., Yu, J., Park, D., Ha, J., Son, K., Lee, S., Chung, M., Kim, H.-Y., & Jeon, N. L. (2018) · Lab on a Chip · doi:10.1039/c8lc00336j · Cited by 99 · see citing works
Self-citationA 3D Printed Hanging Drop Dripper for Tumor Spheroids Analysis Without Recovery
Zhao, L., Xiu, J., Liu, Y., Zhang, T., Pan, W., Zheng, X. S., & Zhang, X. (2019) · Scientific Reports · doi:10.1038/s41598-019-56241-0 · Cited by 98 · see citing works
Liu, S., Kumari, S., He, H., Mishra, P., Singh, B. N., Singh, D., Liu, S., Srivastava, P., & Li, C. (2023) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115285 · Cited by 99 · see citing works
Tissue-engineered 3D melanoma model with blood and lymphatic capillaries for drug development
Bourland, J., Fradette, J., & Auger, F. A. (2018) · Scientific Reports · doi:10.1038/s41598-018-31502-6 · Cited by 94 · see citing works
3D Bioprinted Vascularized Tumour for Drug Testing
Han, S., Kim, S., Chen, Z., Shin, H. K., Lee, S.-Y., Moon, H. E., Paek, S. H., & Park, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082993 · Cited by 94 · see citing works
Self-citationMicrofluidic-based vascularized microphysiological systems
Lee, S., Ko, J., Park, D., Lee, B., Chung, M., Lee, Y., & Jeon, N. L. (2018) · Lab on a Chip · doi:10.1039/c8lc00285a · Cited by 92 · see citing works
Self-citationIn vitro modeling of solid tumor interactions with perfused blood vessels
Kwak, T. J., & Lee, E. (2020) · Scientific Reports · doi:10.1038/s41598-020-77180-1 · Cited by 91 · see citing works
Du, Y., Wang, Y., Bao, Q., Xu, X., Xu, C., Wang, S., Liu, Q., Liu, F., Zeng, Y., Wang, Y., et al. (2024) · Advanced Materials · doi:10.1002/adma.202412815 · Cited by 94 · see citing works
Tumor-on-a-chip model for advancement of anti-cancer nano drug delivery system
Tian, C., Zheng, S., Liu, X., & Kamei, K. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01552-0 · Cited by 95 · see citing works
Lim, J., Ching, H., Yoon, J., Jeon, N. L., & Kim, Y. (2021) · Nano Convergence · doi:10.1186/s40580-021-00261-y · Cited by 83 · see citing works
Self-citation3D Microfluidic Bone Tumor Microenvironment Comprised of Hydroxyapatite/Fibrin Composite
Ahn, J., Lim, J., Jusoh, N., Lee, J., Park, T., Kim, Y., Kim, J., & Jeon, N. L. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00168 · Cited by 81 · see citing works
Self-citationCell-Based Assays on Microfluidics for Drug Screening
Liu, X., Zheng, W., & Jiang, X. (2019) · ACS Sensors · doi:10.1021/acssensors.9b00479 · Cited by 78 · see citing works
Next-Generation Liver Medicine Using Organoid Models
Akbari, S., Arslan, N., Senturk, S., & Erdal, E. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00345 · Cited by 72 · see citing works
Hwang, D. G., Choi, Y., & Jang, J. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.685507 · Cited by 74 · see citing works
Kim, B. S., Cho, W., Gao, G., Ahn, M., Kim, J., & Cho, D. (2021) · Small Methods · doi:10.1002/smtd.202100072 · Cited by 73 · see citing works
Organ on Chip Technology to Model Cancer Growth and Metastasis
Imparato, G., Urciuolo, F., & Netti, P. A. (2022) · Bioengineering · doi:10.3390/bioengineering9010028 · Cited by 76 · see citing works
Angiogenic biomaterials to promote therapeutic regeneration and investigate disease progression
Ngo, M. T., & Harley, B. A. C. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120207 · Cited by 70 · see citing works
Tumor-on-a-chip platform to interrogate the role of macrophages in tumor progression
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Cooperative Effects of Vascular Angiogenesis and Lymphangiogenesis
Osaki, T., Serrano, J. C., & Kamm, R. D. (2018) · Regenerative Engineering and Translational Medicine · doi:10.1007/s40883-018-0054-2 · Cited by 69 · see citing works
Kumar, V., & Varghese, S. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201801198 · Cited by 68 · see citing works
Engineering tumor vasculature on an injection-molded plastic array 3D culture (IMPACT) platform
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Self-citationNew Advances in the Study of Bone Tumors: A Lesson From the 3D Environment
Cortini, M., Baldini, N., & Avnet, S. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00814 · Cited by 64 · see citing works
Lee, S., Kim, S., Koo, D.-J., Yu, J., Cho, H., Lee, H., Song, J. M., Kim, S., Min, D., & Jeon, N. L. (2020) · ACS Nano · doi:10.1021/acsnano.0c05110 · Cited by 64 · see citing works
Self-citationEngineered Vasculature for Organ-on-a-Chip Systems
Aazmi, A., Zhou, H., Li, Y., Yu, M., Xu, X., Wu, Y., Ma, L., Zhang, B., & Yang, H. (2021) · Engineering · doi:10.1016/j.eng.2021.06.020 · Cited by 65 · see citing works
Kim, D., Hwang, K. S., Seo, E. U., Seo, S., Lee, B. C., Choi, N., Choi, J. H., & Kim, H. N. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202102581 · Cited by 62 · see citing works
Perfusable micro-vascularized 3D tissue array for high-throughput vascular phenotypic screening
Yu, J., Lee, S., Song, J., Lee, B., Kim, S., Choi, H., Kang, H., Hwang, Y., Hong, Y., & Jeon, N. L. (2022) · Nano Convergence · doi:10.1186/s40580-022-00306-w · Cited by 62 · see citing works
Self-citation3D microengineered vascularized tumor spheroids for drug delivery and efficacy testing
Ahn, J., Kim, D., Koo, D.-J., Lim, J., Park, T., Lee, J., Ko, J., Kim, S., Kim, M., Kang, K., et al. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.10.009 · Cited by 64 · see citing works
Self-citationVascularized microfluidic platforms to mimic the tumor microenvironment
Michna, R. J., Gadde, M., Özkan, A., DeWitt, M. R., & Rylander, M. N. (2018) · Biotechnology and Bioengineering · doi:10.1002/bit.26778 · Cited by 60 · see citing works
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Brassard-Jollive, N., Monnot, C., Muller, L., & Germain, S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.594903 · Cited by 58 · see citing works
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Ko, J., Lee, Y., Lee, S., Lee, B., & Jeon, N. L. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201900328 · Cited by 59 · see citing works
Self-citationMazio, C., Casale, C., Imparato, G., Urciuolo, F., & Netti, P. A. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.04.028 · Cited by 53 · see citing works
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Ringquist, R., Ghoshal, D., Jain, R., & Roy, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114003 · Cited by 39 · see citing works
On-Chip Replication of Extremely Early-Stage Tumor Behavior
Li, C., Li, S., Du, K., Li, P., Qiu, B., & Ding, W. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c03740 · Cited by 40 · see citing works
Cattin, S., Ramont, L., & Rüegg, C. (2018) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2018.00097 · Cited by 35 · see citing works
Luque‐González, M. A., Reis, R. L., Kundu, S. C., & Caballero, D. (2020) · Advanced Biosystems · doi:10.1002/adbi.202000045 · Cited by 34 · see citing works
Park, B.-U., Park, S. M., Lee, K., Lee, S. J., Nam, Y. E., Park, H. S., Eom, S., Lim, J. O., Kim, D. S., & Kim, H. K. (2019) · Journal of Tissue Engineering · doi:10.1177/2041731419887833 · Cited by 32 · see citing works
Hayward, K. L., Kouthouridis, S., & Zhang, B. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c01089 · Cited by 31 · see citing works
Engineered fluidic systems to understand lymphatic cancer metastasis
Greenlee, J. D., & King, M. R. (2020) · Biomicrofluidics · doi:10.1063/1.5133970 · Cited by 30 · see citing works
Avnet, S., Lemma, S., Cortini, M., Di Pompo, G., Perut, F., & Baldini, N. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00305 · Cited by 29 · see citing works
Wang, R., Zhang, C., Li, D., & Yao, Y. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1057913 · Cited by 30 · see citing works
Trends in Bone Metastasis Modeling
Laranga, R., Duchi, S., Ibrahim, T., Guerrieri, A. N., Donati, D. M., & Lucarelli, E. (2020) · Cancers · doi:10.3390/cancers12082315 · Cited by 29 · see citing works
Application of Three-dimensional (3D) Tumor Cell Culture Systems and Mechanism of Drug Resistance
Shehzad, A., Ravinayagam, V., AlRumaih, H. S., Aljafary, M. A., Almohazey, D., Almofty, S. A., Al-Rashid, N. A., & Al-Suhaimi, E. A. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191014163923 · Cited by 28 · see citing works
CXCL12 enhances pregnancy outcome via improvement of endometrial receptivity in mice
Koo, H. S., Yoon, M.-J., Hong, S.-H., Ahn, J., Cha, H., Lee, D., Ko, J., Kwon, H., Choi, D. H., Lee, K., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-86956-y · Cited by 27 · see citing works
Self-citationZhao, P., Liu, X., Zhang, X., Wang, L., Su, H., Wang, L., He, N., Zhang, D., Li, Z., Kang, H., et al. (2020) · Lab on a Chip · doi:10.1039/d0lc00493f · Cited by 26 · see citing works
Modeling 3D Human Tumor Lymphatic Vessel Network Using High‐Throughput Platform
Lee, S., Kang, H., Park, D., Yu, J., Koh, S. K., Cho, D., Kim, D., Kang, K., & Jeon, N. L. (2021) · Advanced Biology · doi:10.1002/adbi.202000195 · Cited by 27 · see citing works
Self-citationMicrofluidic Tumor Vasculature Model to Recapitulate an Endothelial Immune Barrier Expressing FasL
Kim, S., Park, J., Kim, J., & Jeon, J. S. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c01542 · Cited by 26 · see citing works
Self-citationChallenges in validation of combination treatment strategies for CRC using patient-derived organoids
Benboubker, V., Ramzy, G. M., Jacobs, S., & Nowak-Sliwinska, P. M. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03173-x · Cited by 28 · see citing works
Fabozzi, A., Sala, F. D., di Gennaro, M., Solimando, N., Pagliuca, M., & Borzacchiello, A. (2021) · Polymer Chemistry · doi:10.1039/d1py01077h · Cited by 25 · see citing works
Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside
Bērziņa, S., Harrison, A., Taly, V., & Xiao, W. (2021) · Cancers · doi:10.3390/cancers13164192 · Cited by 24 · see citing works
Three-dimensional in vitro tissue culture models of brain organoids
Gong, J., Meng, T., Yang, J., Hu, N., Zhao, H., & Tian, T. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113619 · Cited by 24 · see citing works
Vascularized tumor models for the evaluation of drug delivery systems: a paradigm shift
Lopez-Vince, E., Wilhelm, C., & Simón‐Yarza, T. (2024) · Drug Delivery and Translational Research · doi:10.1007/s13346-024-01580-3 · Cited by 21 · see citing works
Ma, Y., Sun, X., Cai, Z., Tu, M., Wang, Y., Ouyang, Q., Yan, X., Jing, G., & Yang, G. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101373 · Cited by 22 · see citing works
Millet, M., Messaoud, R. B., Luthold, C., & Bordeleau, F. (2019) · Micromachines · doi:10.3390/mi10060418 · Cited by 22 · see citing works
Microfluidics for Angiogenesis Research
Costa, L., Reis, R. L., Silva‐Correia, J., & Oliveira, J. M. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-36588-2_7 · Cited by 22 · see citing works
How organ-on-a-chip is advancing cancer research and oncology - a cancer hallmarks’ perspective
Avula, L. R., & Grodzinski, P. A. (2024) · Frontiers in Lab on a Chip Technologies · doi:10.3389/frlct.2024.1487377 · Cited by 21 · see citing works
Zhou, L., Liu, L., Chang, M. A., Ma, C., Chen, W., & Chen, P. (2023) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115064 · Cited by 20 · see citing works
Lim, J., Fang, H., Bupphathong, S., Sung, P.-C., Yeh, C.-E., Huang, W. R., & Lin, C.-H. (2024) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.3c01978 · Cited by 19 · see citing works
Abdollahiyan, P., Oroojalian, F., Baradaran, B., de la Guárdia, M., & Mokhtarzadeh, A. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.06.002 · Cited by 19 · see citing works
In Vitro Models of Blood and Lymphatic Vessels—Connecting Tissues and Immunity
Bogseth, A., Ramirez, A., Vaughan, E., & Maisel, K. (2022) · Advanced Biology · doi:10.1002/adbi.202200041 · Cited by 18 · see citing works
Lee, J., Jung, S., Hong, H. K., Jo, H., Rhee, S., Jeong, Y., Ko, J., Cho, Y. B., & Jeon, N. L. (2024) · Lab on a Chip · doi:10.1039/d3lc01055d · Cited by 18 · see citing works
Self-citationApplication of microscale culture technologies for studying lymphatic vessel biology
Chang, C.-S., Seibel, A. J., & Song, J. W. (2019) · Microcirculation · doi:10.1111/micc.12547 · Cited by 17 · see citing works
Liu, T., Zhou, C., Ji, J., Xu, X., Xing, Z., Shinohara, M., Sakai, Y., Sun, T., Feng, X., Yu, Z., et al. (2023) · Biofabrication · doi:10.1088/1758-5090/ace3f9 · Cited by 18 · see citing works
Microfluidic-based platforms for cell-to-cell communication studies
Zhu, L., Tang, Q., Mao, Z., Chen, H., Wu, L. J., & Qin, Y. (2023) · Biofabrication · doi:10.1088/1758-5090/ad1116 · Cited by 17 · see citing works
Biomimetic cell culture for cell adhesive propagation for tissue engineering strategies
Luo, Q., Shang, K., Zhu, J. F., Wu, Z., Cao, T., Ahmed, A. A. Q., Huang, C., & Xiao, L. J. (2023) · Materials Horizons · doi:10.1039/d3mh00849e · Cited by 17 · see citing works
Liu, Y., Liu, Y., Zheng, X. S., Zhao, L., & Zhang, X. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.201901713 · Cited by 16 · see citing works
Vascularized Lower Respiratory-Physiology-On-A-Chip
Nam, H., Choi, Y., & Jang, J. (2020) · Applied Sciences · doi:10.3390/app10030900 · Cited by 16 · see citing works
Vascular microphysiological systems (MPS): biologically relevant and potent models
Breuil, L., Kitada, A., Yadav, S., Zhou, H., Fujimoto, K., & Yokokawa, R. (2025) · Lab on a Chip · doi:10.1039/d5lc00014a · Cited by 15 · see citing works
Modeling of a fast-response magnetic-sensitive hydrogel for dynamic control of microfluidic flow
Liu, Q., Li, H., & Lam, K. Y. (2018) · Physical Chemistry Chemical Physics · doi:10.1039/c8cp06556j · Cited by 15 · see citing works
Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling
Ahmed, T. (2023) · In vitro models · doi:10.1007/s44164-023-00043-2 · Cited by 14 · see citing works
Mazzaglia, C., Munir, H., Lei, I. M., Gerigk, M., Huang, Y. Y. S., & Shields, J. D. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202303720 · Cited by 14 · see citing works
Ahn, J., Sei, Y. J., Jeon, N. L., & Kim, Y. (2018) · IEEE Transactions on Nanotechnology · doi:10.1109/tnano.2017.2771426 · Cited by 14 · see citing works
Self-citationKoo, H. S., Yoon, M.-J., Hong, S.-H., Ahn, J., Cha, H., Lee, D., Park, C. W., & Kang, Y. (2021) · Reproductive Sciences · doi:10.1007/s43032-021-00496-4 · Cited by 14 · see citing works
Self-citationStromal regulation of tumor-associated lymphatics
Munir, H., Mazzaglia, C., & Shields, J. D. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.08.001 · Cited by 14 · see citing works
Exploring Endothelial Expansion on a Chip
Konopka, J., Kołodziejek, D., Flont, M., Żuchowska, A., Jastrzębska, E., & Brzózka, Z. (2022) · Sensors · doi:10.3390/s22239414 · Cited by 13 · see citing works
Marx, U., Accastelli, E., David, R. M., Erfurth, H., Koenig, L., Lauster, R., Ramme, A. P., Reinke, P., Volk, H., Winter, A., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.728866 · Cited by 13 · see citing works
A Novel Tumor on Chip Mimicking the Breast Cancer Microenvironment for Dynamic Drug Screening
Testa, M., Gaggianesi, M., D’Accardo, C., Porcelli, G., Turdo, A., Marco, C. D., Patella, B., Franco, S. D., Modica, C., Bella, S. D., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031028 · Cited by 11 · see citing works
Han, Y., Sengupta, S., Lee, B. J., Cho, H., Kim, J., Choi, H. G., Dash, U., Kim, J. H., Kim, N. D., Kim, J. H., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01025 · Cited by 11 · see citing works
Doty, D. T., Schüler, J. B., Mott, V. L., Bryan, C. M., Moore, N. F., Ho, J. C., & Borenstein, J. T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186478 · Cited by 10 · see citing works
Shin, D. S., Schroeder, M. E., & Anseth, K. S. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202101592 · Cited by 10 · see citing works
Song, S., Li, B., Carvalho, M. R., Wang, H., Mao, D., Wei, J., Chen, W., Weng, Z.-H., Chen, Y., Deng, C., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108276 · Cited by 10 · see citing works
- Authors
- Chung, M., Ahn, J., Son, K., Kim, S., & Jeon, N. L.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Jeon, Noo Li
- Venue
- Advanced Healthcare Materials
- Publisher
- Wiley
- Published
- 2017-05-24
- Volume
- 6
- Issue
- 15
- ISSN
- 2192-2640 (ISSN-L)
- 2192-2659
- OpenAlex
- W2620210433
- Cited by
- 126
- References
- 46
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 14 · 2023: 10 · 2022: 14 · 2021: 23 · 2020: 23 · 2019: 18 · 2018: 14 · 2017: 1
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Healthcare Materials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science, ICT and Future Planning (NRF‐2015R1A2A1A09005662, 2016R1A4A1010796)
- Seoul National University
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- tumor microenvironment, biomimetic systems, microfluidic platform, tumor-stroma interactions, extracellular matrix, paracrine signaling, co-culture, fibroblasts, cancer cell lines, angiogenesis, lymphangiogenesis, chemoresistance
- MeSH terms
- Equipment Design, Humans, Materials Testing, Neoplasms, Experimental, Equipment Failure Analysis, Tissue Engineering, Biomimetic Materials, Cell Line, Tumor, Lab-On-A-Chip Devices, Tumor Microenvironment, Batch Cell Culture Techniques
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