Integrative Biomedical Research
Integrative Biomedical Research (Journal of Angiotherapy) | Online ISSN 3068-6326
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Volume 10 Number 1 2026
REVIEWS (Open Access)
Organoid-on-Chip Platforms as Predictive Models of Human Disease: Promise and Pitfalls
Usha Subbiah1*, Harini Venkata Subbiah1,
Integrative Biomedical Research 10 (1) 1-8 https://doi.org/10.25163/biomedical.10110881
Submitted: 03 November 2025 Revised: 01 January 2026 Accepted: 08 January 2026 Published: 10 January 2026
Abstract
Drug development still runs into what many in the field have come to call the preclinical valley of death — the uncomfortable reality that close to 90% of candidates clearing animal and two-dimensional (2D) testing nevertheless fail once they reach human trials. Static three-dimensional (3D) organoids narrowed, but did not close, this gap, remaining bounded by passive-diffusion limits, immature phenotypes, and considerable batch-to-batch variability. We performed a structured narrative synthesis of peer-reviewed literature, retrieved information following a reproducible search-and-screening protocol, to characterize the biological principles, microengineering strategies, disease-modeling applications, and artificial intelligence (AI) integration of organoid-on-chip (OoC) platforms. Convective perfusion, physiologically tuned fluid shear stress, cyclic strain, and tunable viscoelastic hydrogels emerged as central, organ-specific drivers of structural and functional maturation across brain, kidney, liver, gut, cardiac, and tumor chips. AI and machine-learning pipelines — from convolutional neural networks for segmentation to deep reinforcement learning for closed-loop homeostasis — now support scalable, increasingly reproducible operation, and patient-derived organoid trials are beginning to inform regulatory and clinical decisions. Organoid-on-chip platforms constitute a biologically grounded, increasingly AI-augmented alternative to conventional preclinical models. Full clinical and industrial integration, however, will depend on resolving vascularization deficits, polydimethylsiloxane (PDMS) drug adsorption, standardization gaps, and cost barriers. Keywords: organoid-on-chip; microphysiological systems; organ-on-chip; disease modeling; artificial intelligence; drug screening; precision medicine
References
Acar, A. (2025). Patient-derived tumor organoids (PDTOs) as functional representatives of individual patients in personalized oncology. Frontiers in Medicine, 12, 1733668. https://doi.org/10.3389/fmed.2025.1733668
Aceves, J. O., Grady, W. M., et al. (2022). 3D proximal tubule-on-chip model derived from kidney organoids with improved drug uptake. Scientific Reports, 12, 14997. https://doi.org/10.1038/s41598-022-14997-z
Al-Kabani, A., Huda, B., Haddad, J., Yousuf, M., Bhurka, F., Ajaz, F., Patnaik, R., Jannati, S., & Banerjee, Y. (2025). Exploring experimental models of colorectal cancer: A critical appraisal from 2D cell systems to organoids, humanized mouse avatars, organ-on-chip, CRISPR engineering, and AI-driven platforms—challenges and opportunities for translational precision oncology. Cancers, 17(9), 2163. https://doi.org/10.3390/cancers17092163
Balkhair, O., & Albalushi, H. (2025). Artificial intelligence in organoid-based disease modeling: A new frontier in precision medicine. Biomimetics, 10(12), 845. https://doi.org/10.3390/biomimetics10120845
Bas-Cristóbal Menéndez, A., Du, Z., van den Bosch, T. P. P., Othman, A., Gaio, N., Silvestri, C., & van der Meer, A. D. (2022). Creating a kidney organoid-vasculature interaction model using a novel organ-on-chip system. Scientific Reports, 12, 20699. https://doi.org/10.1038/s41598-022-24945-5
Bauer, S., Wennberg Huldt, C., Kanebratt, K. P., et al. (2017). Functional coupling of human pancreatic islets and liver spheroids on-a-chip. Scientific Reports, 7, 14620. https://doi.org/10.1038/s41598-017-14620-x
Carvalho, M. R., Yan, L.-P., Li, B., Zhang, C.-H., He, Y.-L., Reis, R. L., & Oliveira, J. M. (2023). Organoids-on-a-chip: Different concepts of union between microfluidic devices and organoids—Advances and translation into the clinics. Biofabrication, 15(4), 042004. https://doi.org/10.1088/1758-5090/acf8fb
Castiglione, H., Vigneron, P.-A., Baquerre, C., Yates, F., Rontard, J., & Honegger, T. (2022). Human brain organoids-on-chip: Advances, challenges, and perspectives for preclinical applications. Pharmaceutics, 14(11), 2301. https://doi.org/10.3390/pharmaceutics14112301
Chauhdari, T., Zaidi, S. A., Su, J., & Ding, Y. (2025). Organoids meet microfluidics: Recent advancements, challenges, and future of organoids-on-chip. In Vitro Models, 4, 71–88. https://doi.org/10.1007/s44164-025-00086-7
Fanizza, F., Campanile, M., Forloni, G., Giordano, C., & Albani, D. (2022). Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders. Journal of Tissue Engineering, 13, 1–20. https://doi.org/10.1177/20417314221095339
Geng, Q., Xu, Y., Hu, Y., Wang, L., Wang, Y., Fan, Z., & Kong, D. (2024). Progress in the application of organoids-on-a-chip in diseases. Organogenesis, 20, 2386727. https://doi.org/10.1080/15476278.2024.2386727
Goldrick, G., Guri, I., Herrera-Oropeza, H., O'Brien-Gore, C., Roy, R., Wojtynska, M., & Spagnoli, F. M. (2023). Multicellular systems, organoids, assembloids, and organ-on-chip platforms: Emerging models to study cell-cell interactions in tissue development and disease. Frontiers in Cell and Developmental Biology, 11, 1083175. https://doi.org/10.3389/fcell.2023.1083175
Gunti, S., Hoke, A. T. K., Vu, K., & London, N. R., Jr. (2021). Organoid and spheroid tumor models: Techniques and applications. Cancers, 13, 874. https://doi.org/10.3390/cancers13040874
Homan, K. A., Gupta, N., Kroll, K. T., Kolesky, D. B., Skylar-Scott, M., Miyoshi, T., Mau, D., Valerius, M. T., Ferrante, T., Bonventre, J. V., & Lewis, J. A. (2019). Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nature Methods, 16, 255–262. https://doi.org/10.1038/s41592-019-0325-y
Hu, W., & Lazar, M. A. (2022). Modelling metabolic diseases and drug response using stem cells and organoids. Nature Reviews Endocrinology, 18(12), 744–759. https://doi.org/10.1038/s41574-022-00733-z
Kanabekova, P., Kadyrova, A., & Kulsharova, G. (2022). Microfluidic organ-on-a-chip devices for liver disease modeling in vitro. Micromachines, 13, 428. https://doi.org/10.3390/mi13030428
Karra, N., Fernandes, J., James, J., Swindle, E. J., & Morgan, H. (2023). The effect of membrane properties on cell growth in an 'airway barrier on a chip'. Organs-on-a-Chip, 5, 100025. https://doi.org/10.1016/j.ooc.2022.100025
Lee, H. N., Choi, Y. Y., Kim, J. W., Lee, Y. S., Choi, J. W., Kang, T., & Jeong, G. S. (2021). Effect of biochemical and biomechanical factors on vascularization of kidney organoid-on-a-chip. Nano Convergence, 8, 35. https://doi.org/10.1186/s40580-021-00285-4
Leung, D., Kaur, J., Richardson, G., & Jardé, T. (2025). Reconstituting the solid tumor microenvironment with vascular perfusion on-chip: Advanced modeling for immunotherapy. Critical Reviews in Oncology/Hematology, 205, 104523. https://doi.org/10.1016/j.critrevonc.2025.104523
Li, Y.-J., & Zhong, Y.-Y. (2026). Organoid and organ-on-a-chip (OoC) as transformative in vitro platforms for biomedical research: Recapitulation of native mechanical microenvironments. Nano Research, 19(7), 94908549. https://doi.org/10.26599/NR.2026.94908549
Liu, K., Chen, X., Fan, Z., Ren, F., Liu, J., & Hu, B. (2025). From organoids to organoids-on-a-chip: Current applications and challenges in biomedical research. Chinese Medical Journal, 138(7), 792–807. https://doi.org/10.1097/CM9.0000000000003535
Liu, S., Kumari, S., He, H. Y., & Zhang, Y. S. (2023). Biosensors integrated 3D organoid/organ-on-a-chip system: A real-time biomechanical, biophysical, and biochemical monitoring approach. Biosensors and Bioelectronics, 231, 115285. https://doi.org/10.1016/j.bios.2023.115285
Luce, E., & Duclos-Vallee, J.-C. (2025). Stem cells and organoids: A paradigm shift in preclinical models toward personalized medicine. Pharmaceuticals, 18(7), 992. https://doi.org/10.3390/ph18070992
Mirlohi, M. S., Hamdi, E., Karimi, M. H., Salami, S., Aref, A. R., Kohan, H. G., Ghayoor, A., Seyfoori, A., & Akbari, M. (2026). Tumor organoids-on-a-chip and the role of AI in predictive oncology and personalized cancer medicine. Biofabrication, 18(2), 022005. https://doi.org/10.1088/1758-5090/ad4c08
Morrison, A. I., Sjoerds, M. J., Vonk, L. A., Gibbs, S., & Koning, J. J. (2024). In vitro immunity: An overview of immunocompetent organ-on-chip models. Frontiers in Immunology, 15, 1373186. https://doi.org/10.3389/fimmu.2024.1373186
Mugaanyi, J., Huang, J., Fang, J., Musinguzi, A., Lu, C., & Chen, Z. (2025). Developments and applications of liver-on-a-chip technology—Current status and future prospects. Biomedicines, 13, 1272. https://doi.org/10.3390/biomedicines13061272
Musah, S., Mammoto, A., Ferrante, T. C., Jeanty, S. S. F., Hirano-Kobayashi, M., Mammoto, T., Roberts, K., Chung, S., Novak, R., Ingram, M., & Ingber, D. E. (2017). Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nature Biomedical Engineering, 1, 0069. https://doi.org/10.1038/s41551-017-0069
Papamichail, L., Koch, L. S., Veerman, D., Broersen, K., & van der Meer, A. D. (2025). Organoids-on-a-chip: Microfluidic technology enables culture of organoids with enhanced tissue function and potential for disease modeling. Frontiers in Bioengineering and Biotechnology, 13, 1515340. https://doi.org/10.3389/fbioe.2025.1515340
Patra, R., et al. (2026). Integrating human intestinal organoids into FDA's New Approach Methodologies for drug safety assessment. Advanced Science, 20(3), 2522276. https://doi.org/10.1002/advs.202522276
Powell, R. T., Dhruv, H., et al. (2022). Non-invasive viability screening of 3D colorectal cancer organoids using AutoML brightfield deep learning profiles. Lab on a Chip, 22, 4118–4132. https://doi.org/10.1039/D2LC00393G
Saini, R., Thakur, B., Basaba, B. K., & Satapathy, M. K. (2026). Artificial intelligence–enabled organoid platforms for precision medicine: Integrating multi-omics, digital twins, and microphysiological systems. Organoids, 5, 20. https://doi.org/10.3390/organoids5010020
Spitz, S., Bolognin, S., Brandauer, K., et al. (2022). Development of a multi-sensor integrated midbrain organoid-on-a-chip platform for studying Parkinson's disease. bioRxiv. https://doi.org/10.1101/2022.08.19.504522
Sun, D., Gao, W., Hu, H., & Zhou, S. (2022). Why 90% of clinical drug development fails and how to improve it? Acta Pharmaceutica Sinica B, 12(7), 3049–3062. https://doi.org/10.1016/j.apsb.2022.02.002
Wang, H., Ning, X., Zhao, F., Zhao, H., & Li, D. (2024). Human organoids-on-chips for biomedical research and applications. Theranostics, 14(3), 788–818. https://doi.org/10.7150/thno.90492
Wang, P., Santoso, B., He, S., Tuan, R. S., & Li, Z. A. (2026). AI-integrated organoids and organoids-on-chips: A unifying framework for model-as-evidence pathways and automated computational design. International Journal of AI for Materials and Design. https://doi.org/10.36922/IJAMD026150008
Wang, Y., Wang, L., Zhu, Y., & Qin, J. (2018). Human brain organoid-on-a-chip to model prenatal nicotine exposure. Lab on a Chip, 18, 851–860. https://doi.org/10.1039/c7lc01084b
Yang, J., Jiang, Y., Li, M., Wu, K., Wei, S., Zhao, Y., Shen, J., Du, F., Chen, Y., Deng, S., Xiao, Z., Du, Y., Wu, X., & Yuan, W. (2025). Progress in the application of organoid and organ-on-a-chip (OOAC) models in medical and traditional Chinese medicine research: From cellular heterogeneity to multi-organ system prediction. Chinese Medicine, 20, 22. https://doi.org/10.1186/s13020-025-01071-8
Yao, Q., Cheng, S., Pan, Q., Yu, J., Cao, G., Li, L., & Cao, H. (2024). Organoids: Development and applications in disease models, drug discovery, precision medicine, and regenerative medicine. MedComm, 5(10), e735. https://doi.org/10.1002/mco2.735
Zhang, H., Huang, N., Bian, S., & Sawan, M. (2025). Brain organoids-on-chip for neural diseases modeling: History, challenges and trends. Journal of Pharmaceutical Analysis, 15(3), 101323. https://doi.org/10.1016/j.jpha.2025.101323
Zhao, X., Gao, J., Liu, Y., Shi, T., Zhang, L., Zhang, X., & Chen, J. (2025). Application cases and clinical relevance of tumor organoid models in immunotherapy drug screening and immune-tumor interface modeling. Frontiers in Immunology, 16, 1723995. https://doi.org/10.3389/fimmu.2025.1723995
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