Organs-on-a-chip: a union of tissue engineering and microfabrication
Open accessAbstract
We review the emergence of the new field of organ-on-a-chip (OOAC) engineering, from the parent fields of tissue engineering and microfluidics. We place into perspective the tools and capabilities brought into the OOAC field by early tissue engineers and microfluidics experts. Liver-on-a-chip and heart-on-a-chip are used as two case studies of systems that heavily relied on tissue engineering techniques and that were amongst the first OOAC models to be implemented, motivated by the need to better assess toxicity to human tissues in preclinical drug development. We review current challenges in OOAC that often stem from the same challenges in the parent fields, such as stable vascularization and drug absorption.
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Self-citationDesign and Fabrication of Biological Wires for Cardiac Fibrosis Disease Modeling
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Integrating organoids and organ-on-a-chip devices
Zhao, Y., Landau, S., Okhovatian, S., Liu, C., Lu, R. X. Z., Lai, B. F. L., Wu, Q., Kieda, J., Cheung, K., Rajasekar, S., et al. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00207-z · Cited by 206 · see citing works
“Similar principles in OoCs exist, except that OoC approaches are focused on a smaller scale 45 (Fig.”
Self-citationMolecular mechanisms in liver repair and regeneration: from physiology to therapeutics
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Engineering Organ-on-a-Chip Systems for Vascular Diseases
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Self-citationRoadblocks confronting widespread dissemination and deployment of Organs on Chips
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“While the foundationaluse of Organson Chipscan beattributedtotheacademic convergence of micro fl uidics, stem cell technology and tissue engineering 44,45 , one of the major current driving forces is the interest of pharmaceutical companies in applying this technology to drug development.”
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“Similarly, OoC devices replicate human organ functions, providing new avenues for research into human physiology by mimicking organ functionalities in a controlled microscale environment [4].”
Advances in cardiac tissue engineering and heart‐on‐a‐chip
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Self-citationFrom organoids to organoids-on-a-chip: Current applications and challenges in biomedical research
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“[7,8,43] Although microfluidic and tissue engineering technologies have been established, organ-on-a-chip technology advanced in parallel with organoids.”
InfluentialAdvances in 3D Organoids and Organ‐on‐a‐Chip Systems for Biomedical Research
Sakthivel, V., Dharshan, S. S., Namasivayam, S. K. R., & Arockiaraj, J. (2026) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbma.70028 · Cited by 47 · see citing works
On-chip recapitulation of the tumor microenvironment: A decade of progress
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Advances in human organs-on-chips and applications for drug screening and personalized medicine
Zhou, C., Li, Z., Lu, K., Liu, Y., Xuan, L., Mao, H., & Wang, X. (2024) · Fundamental Research · doi:10.1016/j.fmre.2023.12.019 · Cited by 40 · see citing works
“Additionally, 3D printing of molds, devices, and even biological tissues offers a solution to the throughput challenge [139] .”
Bodenstein, D. F., Siebiger, G., Zhao, Y., Clasky, A. J., Mukkala, A. N., Beroncal, E. L., Banh, L., Aslostovar, L., Brijbassi, S., Hogan, S. E., et al. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03771-8 · Cited by 39 · see citing works
Self-citationBiomimetic hepatic lobules from three-dimensional imprinted cell sheets
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Self-citationDirect laser writing photonic crystal hydrogel sensors for in-situ sensing in microfluidic device
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Hydrogel-Based Strategies for Liver Tissue Engineering
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Advances in cardiac organoid research: implications for cardiovascular disease treatment
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Developing Liver Microphysiological Systems for Biomedical Applications
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Self-citationSkeletal Muscle Tissue Engineering: From Tissue Regeneration to Biorobotics
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“For a more in-depth analysis, we refer interested readers to previously published reviews [ 93 , 94 , 97 ].”
Actuation for flexible and stretchable microdevices
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Tuneable hydrogel patterns in pillarless microfluidic devices
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Bioengineering vascularization
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Self-citationConstruction of dentin-on-a-chip based on microfluidic technology and tissue engineering
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Trends in organ-on-a-chip for pharmacological analysis
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Microenvironments Matter: Advances in Brain-on-Chip
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“Efforts in improving technical platforms and chip-based assays should be guided by the merged activities in tissue engineering and microfluidics that already took place in developing Organ-on-Chip (OoC) models over the last 25 years [10].”
BackgroundBiomimetic Liver Lobules from Multi‐Compartmental Microfluidics
Huang, D., Wu, Z., Wang, J., Wang, J., & Zhao, Y. (2024) · Advanced Science · doi:10.1002/advs.202406573 · Cited by 17 · see citing works
Self-citationBiomimetic cell culture for cell adhesive propagation for tissue engineering strategies
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Bioinspired Materials for Wearable Diagnostics and Biosensors
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Self-citationMicroscale tissue engineering of liver lobule models: advancements and applications
Wang, Q., Liu, J., Yin, W., Wang, A., Zheng, J., Wang, Y., & Dong, J. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1303053 · Cited by 15 · see citing works
Advances in Microfluidic Bioprinting for Multi-Material Multi-Cellular Tissue Constructs
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The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity
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“AP data are particularly valuable for generating computational models of cell cultures, where the effects of drugs can predict the behaviour of the CMs [148,149].”
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“It is based on the knowledge generated by the fields of tissue engineering and microfluidics, while heavily relying on different microfabrication technologies [1].”
Rodríguez, C. F., Quezada, V., Guzmán-Sastoque, P., Orozco, J. C., Reyes, L. H., Osma, J. F., Muñoz-Camargo, C., & Cruz, J. C. (2025) · Scientific Reports · doi:10.1038/s41598-025-04495-2 · Cited by 10 · see citing works
Stimulus-assisted in situ bioprinting: advancing direct bench-to-bedside delivery
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“Through optical light-scatter biosensing, architectural changes derived from TNF-a -induced in fl ammation were reliably detected in a non-invasive manner, while maintaining a stable culture for over a week (39).”
Advancements in Microfluidic Organ-on-a-chip for Oral Medicine
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“4,8,9 Before building an OoC, it’s important to understand the physiological structure of the target organ or tissue, as well as its unique biochemical and physical environment.”
Lessons Learned from Liver-on-Chip Platform
Razavi, Z. S., Razavi, F. S., Soltani, M., Pazoki–Toroudi, H., Farokhi, S., Azimi, I., & Ahmadi, N. (2025) · Annals of Biomedical Engineering · doi:10.1007/s10439-025-03779-y · Cited by 7 · see citing works
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Self-citationAdvances and Applications of Organ-on-a-Chip and Tissue-on-a-Chip Technology
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“Currently, regenerative therapies for cardiac, respiratory, and hematopoietic are under development with strong potential for translational studies [26].”
Dey, S., Kinoshita, M., Puttick, S. G., Rose, S., Trau, M., Roberts, M. J., & Koo, K. M. (2024) · Advanced Sensor Research · doi:10.1002/adsr.202300193 · Cited by 7 · see citing works
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“Organ-on-a-chip (OoC) technology promises to revolutionize biomedical research and drug development by providing more accurate and ethical human models for testing the efficacy and safety of drugs and treatments [1–3].”
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Self-citationShirzad, M., Kang, J., Bodaghi, M., & Nam, S. Y. (2025) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2025.111143 · Cited by 6 · see citing works
Gut-on-a-Chip-Based Real-Time miRNA-21 Monitoring and Anti-Inflammatory Drug Evaluation
Xu, Z., Ding, J., Meng, Q., Wang, K., Li, H., Meng, F., Han, J., & Wang, L. (2025) · ACS Sensors · doi:10.1021/acssensors.5c00957 · Cited by 5 · see citing works
Vesmaker, K., Venkadakrishnan, J., & Dhar, A. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178356 · Cited by 4 · see citing works
Mechano-Organ-on-Chip for Cancer Research
Wang, L., Cheung, J. C., Zhao, X., Khoo, B. L., & Wong, S. H. D. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27031330 · Cited by 7 · see citing works
“…leverages microfabrication, microfluidics, and engineered biomaterials to create microphysiological systems that recapitulate key organ-level functions, incorporating controlled fluid flow, mechanical forces, multiple tissue interfaces, and three-dimensional architecture with human cells [17–19].”
Angiogenic Imbalance Models of Preeclampsia: From Mechanisms to Clinics
Akbarzadeh, I., Heidari, F., Nwoke, S. O., Liu, C., Jankovic‐Karasoulos, T., & McClements, L. (2026) · Hypertension · doi:10.1161/hypertensionaha.125.26316 · Cited by 4 · see citing works
Vascularized Organoid-on-Chip Platforms: Expanding the Bioengineering Frontiers with Microfluidics
Konwarh, R. (2025) · Biomaterials Connect · doi:10.69709/biomatc.2025.155652 · Cited by 4 · see citing works
Lab-on-chip technology for clinical and medical application
Jeyaraman, M., Jeyaraman, N., Ramasubramanian, S., Iyengar, K. P., & Jain, V. K. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-24790-3.00018-1 · Cited by 4 · see citing works
Artificial Intelligence Applications in Healthcare
Durrah, O., Aldhmour, F. M., El‐Maghraby, L., & Chakir, A. (2024) · Synthesis lectures on engineering, science, and technology · doi:10.1007/978-3-031-50300-9_10 · Cited by 4 · see citing works
Bioengineered intestinal models: structural precision drives functional and microbial fidelity
Gao, Z., Du, H., Yu, S., Li, Q., Li, Y., Yin, J., Yang, H., Wang, Y., Zhou, H., & Shen, L. (2025) · Bio-Design and Manufacturing · doi:10.1631/bdm.2500353 · Cited by 3 · see citing works
Organ-on-a-Chip and Lab-on-a-Chip Technologies in Cardiac Tissue Engineering
Marazzi, D., Trovalusci, F., Nardo, P. D., & Carotenuto, F. (2025) · Biomimetics · doi:10.3390/biomimetics11010018 · Cited by 3 · see citing works
Learning about liver regeneration from liver-on-a-chip
Ortega‐Ribera, M. (2024) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2024.100533 · Cited by 3 · see citing works
Advancements in Organ‐on‐a‐Chip Systems: Materials, Characterization, and Applications
Gunasekaran, B. M., Srinivasan, S., Ezhilan, M., Rajagopal, V., & Nesakumar, N. (2024) · ChemistrySelect · doi:10.1002/slct.202403611 · Cited by 3 · see citing works
Current Researches in Modular Biofabrication: Tissue Building Blocks and Bioreactors
Zakhireh, S., Mesgari-Shadi, A., Barar, J., Omidi, Y., Beygi‐Khosrowshahi, Y., & Adibkia, K. (2024) · Korean Journal of Chemical Engineering · doi:10.1007/s11814-024-00059-8 · Cited by 3 · see citing works
From 3D culture to clinical decision-making: Systematic innovations in breast cancer organoids
Hu, M., Zhou, C., Li, M., & Zhao, J. (2025) · Biomaterials Advances · doi:10.1016/j.bioadv.2025.214528 · Cited by 2 · see citing works
Recapitulating Endochondral Ossification for Bone Repair: From Development to Engineering Strategy
Su, Y., He, Z., Chen, Q., Chen, L., Wei, C., Zhou, Z., Lin, J., Li, H., & Xing, D. (2026) · Advanced Healthcare Materials · doi:10.1002/adhm.71155 · Cited by 2 · see citing works
From concept to context-of-use: A framework for Organ-on-Chip development
Araújo‐Gomes, N., Middelkamp, H. H. T., Loessberg-Zahl, J., Raaij, J. V. D. E., van der Meer, A. D., & Middendorp, S. (2026) · NAM journal. · doi:10.1016/j.namjnl.2026.100097 · Cited by 2 · see citing works
Immune-stromal interactions at the crossroads of tissue injury, repair, and tumor progression
Ning, D., Tavakol, D. N., Graney, P. L., Lee, E., Hung, C. T., & Vunjak‐Novakovic, G. (2026) · Med · doi:10.1016/j.medj.2026.101222 · Cited by 2 · see citing works
Sun, A. Y., Lin, C. H., Tatka, J. A., Drake, K., Daily, S., Castellanos, M., Nelson, A., & Olanrewaju, A. O. (2025) · Progress in Additive Manufacturing · doi:10.1007/s40964-025-01081-w · Cited by 2 · see citing works
“Unlike biohybrid materials used in tissue engineering, for which the polymeric materials serve primarily as scaffolds for the cells [6, 7], this emerging class of materials leverages engineered microbes as micro-factories to produce the material or modulate the functions of the material.”
In Vitro Models for Drug Delivery Systems
Kour, S. S., Khandelwal, S., Roshni, & Yadav, V. (2025) · Methods in pharmacology and toxicology · doi:10.1007/978-1-0716-4554-3_23 · Cited by 2 · see citing works
Aijaz, M., Ahmad, S., & Alam, S. (2025) · Journal of Clinical Medicine of Kazakhstan · doi:10.23950/jcmk/16880 · Cited by 2 · see citing works
Human Toxicity of Nano‐ and Microplastics
Cruz‐Salas, A. A., Velasco-Pérez, M., Bobadilla, A. L. T., Vázquez‐Morillas, A., & Valdemar, R. M. E. (2024) · doi:10.1002/9781394238163.ch15 · Cited by 2 · see citing works
Joint‐on‐a‐Chip: The Future of Preclinical Modelling of Joint Diseases
Pye, J. S., Zhang, Y., Lin, X., Yousefi, M., Wen, C., & Li, J. J. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202504487 · Cited by 1 · see citing works
“…culture media through the corresponding tissue channels, where the temporal delivery of biomolecules, such as growth factors, can enhance tissue morphogenesis and maturity or modulate tissue responses, for instance, with relevance to specific diseases or treatment modalities [22–24].”
Organ-on-a-Chip Devices to Simulate the Dentin-Pulp Complex: A Qualitative Systematic Review
Baeza-Fernández, J., & Bucchi, C. (2026) · Annals of Biomedical Engineering · doi:10.1007/s10439-026-04058-0 · Cited by 1 · see citing works
“Two studies used soft lithography [18, 22], which enables the creation of high-resolution micro-structures but has certain limitations, such as requiring a cleanroom environment, being time-consuming, and incurring high costs [4, 11, 24].”
Human hair regeneration using organoids and hair-on-chip technologies
Ahmed, I. A., & Shafiee, A. (2026) · Lab on a Chip · doi:10.1039/d6lc00095a · Cited by 1 · see citing works
Ying, S., Xu, H., Xu, Y., & Mi, X. (2026) · Molecules · doi:10.3390/molecules31091520 · Cited by 1 · see citing works
“Infliximab is a monoclonal antibody that specifically neutralizes TNF-α [39–41].”
Sun, D., Katare, R., Sethu, P., Cheng, P., & Fan, Y. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1371074
Body on a Chip Development Based on Nano/Microfabrication
Hirai, Y. (2023) · Journal of the Japan Society for Precision Engineering · doi:10.2493/jjspe.89.690
Watkins, A. R., Alarcon, E. I., Suuronen, E. J., & Ruel, M. (2025) · Journal of the American College of Surgeons · doi:10.1097/xcs.0000000000001430
Genetically modified cell membrane proteins in tissue engineering and regenerative medicine
Bao, Y., Hu, Y., Hao, M., Zhang, Q., Yang, G., & Jiang, Z. (2025) · Biofabrication · doi:10.1088/1758-5090/add625
“These models are derived from human pluripotent or adult stem cells, enabling researchers to better understand the functions of natural organs and therapeutic effects, while more accurately simulating human physiology in vitro [267, 268].”
Charelli, L. E., Ferreira, J. P. D., Sousa-Batista, A. J., & Balbino, T. A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-13403-6.00014-3
Organ-on-chip models for reconstructive tissue engineering: An evolutionary plastic surgery advance
Talha, M., & Khalid, M. (2025) · The International Journal of Artificial Organs · doi:10.1177/03913988251355075
Editorial for the Special Issue on the Application of Microfluidic Technology in Bioengineering
Wang, S., & Shen, Y. (2025) · Micromachines · doi:10.3390/mi16091022
Yang, J., Ren, L., Chen, Y., Zhou, Q., Hu, H., Bian, R., Qiu, P., & Lou, D. (2025) · Materials Today Communications · doi:10.1016/j.mtcomm.2025.114033
Engineering Organs-on-Chips and Organoids from the Perspective of Compartmentalization
Zeng, Y., Gu, Z., Chen, H., & Deng, X. (2025) · Engineering · doi:10.1016/j.eng.2025.12.011
Flow assessment and analysis of oxygen transport in an organ-on-chip platform
Carvalho, V., Rodrigues, N., Rodrigues, R., Teixeira, S., & Lima, R. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-24066-9.00021-0
Artificial gametes: A nanotechnology-driven future
Natarajan, V., Dalal, A., Tippani, R., Billah, A. A. M., Shaikh, S. S., Chinni, S. V., & Mohandoss, K. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-41561-6.00002-9
Organ-on-Chip Technology for Women’s Health Engineering
Carrillo, C. I. B., & Zambuto, S. G. (2026) · Springer eBooks · doi:10.1007/978-3-032-10745-9_22
Wang, G., Ding, H., & Gu, Z. (2026) · Med-X · doi:10.1007/s44258-026-00089-3
“By integrating micrometer-scale fluidic channels that mimic vascular networks with three-dimensional (3D) bio-mimetic scaffolds supporting tissue-specific cell co-cultures [2], this technology enables precise control over cellular microenvironments [3].”
Microfluidic chips for biomimetic models
Damiati, S., Damiati, L. A., & Damiati, L. A. (2026) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2026.06.002
Tissue engineering for cosmetics applications
Mínguez, I. M. L., & Dashnyam, K. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-41499-2.00021-5
Han, X., Chen, Q., Li, K., Wu, J., Wang, A., Wang, Y., Zhao, H., & Liu, W. (2026) · Microsystems & Nanoengineering · doi:10.1038/s41378-026-01401-2
“Organs-on-a-chip (OoC) technology bridges the in vitro to in vivo gap by emulating human tissue interfaces, vascular perfusion, and mechanical cues within micro-engineered systems 15,16 .”
Introduction to Tissue Engineering
Zhang, W. (2026) · Springer eBooks · doi:10.1007/978-3-032-32096-4_7
Kang, J., Jin, H., Kim, K. H., Shin, D., Shin, D., Moon, H., & Kim, K.-T. (2026) · Environmental Science & Technology · doi:10.1021/acs.est.6c03280
Three-Dimensional Bioprinting in Reconstructive Plastic Surgery: A Comprehensive Review
Hirani, R., Iraj, S., Trandafirescu, M., Boyd, C. J., & Etienne, M. (2026) · Cells · doi:10.3390/cells15171595
“…organ-on-chip technology, enabling vascularized, multicellular microphysiological models that share vascularization as their central unresolved challenge; in the near term, such patient-specific tissue-on-chip models offer a more tractable translational application than implantable organs [99].”
Ahn, J.-C., Kim, M., Kim, J.-H., Kang, S., Lee, D.-I., Liu, H., Shin, S., Na, K., Jun, Y., Hong, O., et al. (2026) · Advanced Materials · doi:10.1002/adma.74851
Human cardiovascular organoids: Biomedical applications and ethical challenges
Sen, K., Majumder, S., Stanišić, D., & Majumder, A. (2026) · American Heart Journal Plus Cardiology Research and Practice · doi:10.1016/j.ahjo.2026.100882
Quantitative in vitro bioassays for scaffold evaluation
Jose, M. S., & Sumathi, S. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33455-9.00017-1
Sengupta, S., Das, S., Ghosh, T., Mukhopadhay, A., & Basu, B. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33455-9.00009-2
Kamei, K. (2026) · Communications Biology · doi:10.1038/s42003-026-10887-5
“Liver-on-a-chip platforms: extrinsic control without developmental trajectories Liver-on-a-chip platforms excel at imposing extrinsic cues, including perfusion, shear stress, controlled geometry, and compartmentalized co-culture 15,16,82 – 84 .”
Wang, Y., Okhovatian, S., Zhao, Y., Wu, Q., Bodenstein, D. F., & Radisic, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-16110-0.00031-5
Self-citation
- Authors
- Zhao, Y., Wang, E. Y., Lai, F. B. L., Cheung, K., & Radisic, M.
- Affiliations
- University Health Network (CA)
- Koch Institute for Integrative Cancer Research At MIT (US)
- University of Toronto (CA)
- Corresponding author
- Radisic, Milica
- Venue
- Trends in Biotechnology
- Publisher
- Elsevier BV
- Published
- 2023-03
- Volume
- 41
- Issue
- 3
- Pages
- 410-424
- ISSN
- 0167-7799 (ISSN-L)
- PMC
- PMC9985977
- OpenAlex
- W4318712566
- Cited by
- 93
- References
- 124
- Citations by year
- 2026: 24 · 2025: 34 · 2024: 27 · 2023: 8
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 351 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Trends in biotechnology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, other-oa)
- Funders
- Canadian Institutes of Health Research (FDN-167274)
- Natural Sciences and Engineering Research Council of Canada (RGPIN 326982-10)
- Canada Foundation for Innovation
- National Institutes of Health (2R01 HL076485)
- Canada Research Chairs
- Ontario Research Foundation (36442)
- Heart and Stroke Foundation of Canada (G-16-00012711, G-18-0022356)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- organ-on-a-chip, tissue engineering, microfluidics, liver-on-a-chip, heart-on-a-chip, toxicity testing, preclinical drug development, vascularization, drug absorption, microfabrication
- MeSH terms
- Humans, Liver, Tissue Engineering, Microfluidics, Microtechnology, Lab-On-A-Chip Devices
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