{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:51:15Z","timestamp":1790621475712,"version":"4.1.0"},"reference-count":151,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Organoid and organ-on-chip technologies are rapidly evolving platforms for viral research that integrate stem cell biology, tissue engineering, and microfluidics to recapitulate key structural, mechanical, biochemical, and cellular features of human and animal physiology. By incorporating multicellular organoids into perfused microfluidic systems, these models can provide complex, dynamic, and physiologically relevant micro-environments for investigating virus\u2013host interactions that are difficult to capture in conventional two-dimensional cultures and static organoids. Controlled flow, shear stress, extracellular matrix organization, tissue\u2013tissue interfaces, and multicellular signaling enable mechanistic investigation of viral infectivity, dissemination, tissue injury and immune activation. Integration of real-time imaging and biosensors further permits longitudinal monitoring of viral replication, host responses, and tissue integrity, expanding the potential of these platforms for antiviral drug discovery. Recent organoid-on-chip studies using brain, skin, vaginal, respiratory, and intestinal models have demonstrated how tissue architecture, mechanical forces, glycocalyx dynamics, and immune\u2013stromal interactions influence viral tropism and pathogenesis. In this review, we provide a mechanistic and translational overview of organoid and organ-on-chip technologies for studying viral infections, with particular emphasis on models of herpes simplex virus (HSV)-mediated disease. We further examine advances in immune integration, multi-organ systems, biosensing, and computational approaches that are expanding the complexity and predictive potential of these models. Importantly, patient-derived organoids and organ-on-chip platforms can capture interindividual differences in viral susceptibility, host responses, and therapeutic efficacy, providing pharmaceutical research with more precise, patient-relevant data to support drug prioritization and precision antiviral medicine. Finally, we discuss key barriers to broader adoption, including organoid maturation, biological and technical variability, reproducibility, scalability, biosafety, cost, standardization, and regulatory validation. Collectively, these advances position organoid and organ-on-chip technologies as powerful human-relevant models that bridge reductionist in vitro systems and human disease, while continued optimization, standardization, and validation will be essential to realize their full potential for mechanistically informed antiviral discovery, therapeutic development, and precision medicine.<\/jats:p>","DOI":"10.3390\/cells15171514","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:03:41Z","timestamp":1787558621000},"page":"1514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Organoids to Organ-on-Chip: Advancing Human-Relevant Models for Viral Pathogenesis and Antiviral Drug Discovery"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8798-6815","authenticated-orcid":false,"given":"Vaibhav","family":"Tiwari","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Choe","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryan","family":"Vora","sequence":"additional","affiliation":[{"name":"Carl Sandburg High School, Orland Park, IL 60462, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1901-0682","authenticated-orcid":false,"given":"Ishita","family":"Kataki","sequence":"additional","affiliation":[{"name":"Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara A. L.","family":"Roujouleh","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Allenspach","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-6933","authenticated-orcid":false,"given":"Michelle","family":"Swanson-Mungerson","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V.","family":"Volin","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinju","family":"Sundaresan","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1038\/s41564-023-01434-7","article-title":"Understanding virus-host interactions in tissues","volume":"8","author":"Speranza","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hare, D., Collins, S., Cuddington, B., and Mossman, K. (2016). The Importance of Physiologically Relevant Cell Lines for Studying Virus-Host Interactions. Viruses, 8.","DOI":"10.3390\/v8110297"},{"key":"ref_3","first-page":"910","article-title":"2D and 3D cell cultures-a comparison of different types of cancer cell cultures","volume":"14","author":"Kapalczynska","year":"2018","journal-title":"Arch. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.1128\/JVI.03235-12","article-title":"Susceptibility of human iris stromal cells to herpes simplex virus 1 entry","volume":"87","author":"Baldwin","year":"2013","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5185","DOI":"10.1128\/JVI.00109-15","article-title":"A role for 3-O-sulfated heparan sulfate in promoting human cytomegalovirus infection in human iris cells","volume":"89","author":"Baldwin","year":"2015","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chang, K., Majmudar, H., Tandon, R., Volin, M.V., and Tiwari, V. (2022). Induction of Filopodia During Cytomegalovirus Entry Into Human Iris Stromal Cells. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.834927"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.antiviral.2018.11.007","article-title":"A synthetic glycosaminoglycan mimetic blocks HSV-1 infection in human iris stromal cells","volume":"161","author":"Majmudar","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8970","DOI":"10.1128\/JVI.00296-06","article-title":"Role for 3-O-sulfated heparan sulfate as the receptor for herpes simplex virus type 1 entry into primary human corneal fibroblasts","volume":"80","author":"Tiwari","year":"2006","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1083\/jcb.200509155","article-title":"A novel role for phagocytosis-like uptake in herpes simplex virus entry","volume":"174","author":"Clement","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Richter, M., Piwocka, O., Musielak, M., Piotrowski, I., Suchorska, W.M., and Trzeciak, T. (2021). From Donor to the Lab: A Fascinating Journey of Primary Cell Lines. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.711381"},{"key":"ref_11","first-page":"576","article-title":"3D engineered tissue models for studying human-specific infectious viral diseases","volume":"21","author":"Hwang","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1126\/science.aaw7894","article-title":"Organoids-on-a-chip","volume":"364","author":"Park","year":"2019","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"788","DOI":"10.7150\/thno.90492","article-title":"Human organoids-on-chips for biomedical research and applications","volume":"14","author":"Wang","year":"2024","journal-title":"Theranostics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.semcdb.2022.10.001","article-title":"Microfluidic organoids-on-a-chip: The future of human models","volume":"144","author":"Saorin","year":"2023","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e0113225","DOI":"10.1128\/jvi.01132-25","article-title":"Organoids: Physiologically relevant ex vivo models for viral disease research","volume":"99","author":"Wang","year":"2025","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Liu, W., Tang, D., Xu, X.X., Liu, Y.J., and Jiu, Y. (2021). How Physical Factors Coordinate Virus Infection: A Perspective from Mechanobiology. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.764516"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Villenave, R., Wales, S.Q., Hamkins-Indik, T., Papafragkou, E., Weaver, J.C., Ferrante, T.C., Bahinski, A., Elkins, C.A., Kulka, M., and Ingber, D.E. (2017). Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169412"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nmeth.3697","article-title":"Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro","volume":"13","author":"Benam","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9819154","DOI":"10.34133\/2022\/9819154","article-title":"Biomimetic Alveolus-on-a-Chip for SARS-CoV-2 Infection Recapitulation","volume":"2022","author":"Cao","year":"2022","journal-title":"Research"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"011502","DOI":"10.1063\/5.0126541","article-title":"Gut-on-a-chip models for dissecting the gut microbiology and physiology","volume":"7","author":"Valiei","year":"2023","journal-title":"APL Bioeng."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bedos, L., Wickham, H., Gabriel, V., Zdyrski, C., Allbaugh, R.A., Sahoo, D.K., Sebbag, L., Mochel, J.P., and Allenspach, K. (2022). Culture and characterization of canine and feline corneal epithelial organoids: A new tool for the study and treatment of corneal diseases. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.1050467"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"eaeb4864","DOI":"10.1126\/sciadv.aeb4864","article-title":"A microphysiologic human cervical model recapitulates microbial, immune, and pathogenic properties of sexually transmitted infections","volume":"12","author":"Nelson","year":"2026","journal-title":"Sci. Adv."},{"key":"ref_23","first-page":"e66486","article-title":"Modeling Healthy and Dysbiotic Vaginal Microenvironments in a Human Vagina-on-a-Chip","volume":"204","author":"Gulati","year":"2024","journal-title":"J. Vis. Exp."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s40168-022-01400-1","article-title":"Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip","volume":"10","author":"Mahajan","year":"2022","journal-title":"Microbiome"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sundstrom, J., Vanderleeden, E., Barton, N.J., Redick, S.D., Dawes, P., Murray, L.F., Olson, M.N., Tran, K., Chigas, S.M., and Orszulak, A.R. (2024). Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Organoid-Specific Transcripts Associated with Alzheimer\u2019s Disease and Autoimmune Diseases. Cells, 13.","DOI":"10.20944\/preprints202407.1267.v1"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Brun, P., Qesari, M., Marconi, P.C., Kotsafti, A., Porzionato, A., Macchi, V., Schwendener, R.A., Scarpa, M., Giron, M.C., and Palu, G. (2018). Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment. Front. Cell Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00074"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, T., Peng, D., Yao, M., Li, M., Wang, Y., Li, S., Zhang, D., Yang, B., Qiu, H.J., and Li, L.F. (2025). Immune organoids: Emerging platforms for modeling and analyzing human adaptive immunity. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1632117"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116214","DOI":"10.1016\/j.celrep.2025.116214","article-title":"Organoids as models of immune-organ interaction","volume":"44","author":"Harter","year":"2025","journal-title":"Cell Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/s41563-024-02037-1","article-title":"Human immune organoids to decode B cell response in healthy donors and patients with lymphoma","volume":"24","author":"Zhong","year":"2025","journal-title":"Nat. Mater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/s41551-025-01491-9","article-title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response","volume":"10","author":"Ringquist","year":"2025","journal-title":"Nat. Biomed. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s43556-025-00364-6","article-title":"Single-cell sequencing and organoids: Applications in organ development and disease","volume":"6","author":"Li","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"119367","DOI":"10.1016\/j.biomaterials.2019.119367","article-title":"A virus-induced kidney disease model based on organ-on-a-chip: Pathogenesis exploration of virus-related renal dysfunctions","volume":"219","author":"Wang","year":"2019","journal-title":"Biomaterials"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105319","DOI":"10.1016\/j.micinf.2024.105319","article-title":"Organoids and organ-on-chip technology for investigating host-microorganism interactions","volume":"26","author":"Walocha","year":"2024","journal-title":"Microbes Infect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/ibd\/izac212","article-title":"Molecular and Functional Characterization of Human Intestinal Organoids and Monolayers for Modeling Epithelial Barrier","volume":"29","author":"Jelinsky","year":"2023","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e735","DOI":"10.1002\/mco2.735","article-title":"Organoids: Development and applications in disease models, drug discovery, precision medicine, and regenerative medicine","volume":"5","author":"Yao","year":"2024","journal-title":"MedComm"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Abdal Dayem, A., Kwak, Y., Jeun, H., and Cho, S.G. (2025). Recent Insights into Organoid-Derived Extracellular Vesicles and Their Biomedical Applications. J. Pers. Med., 15.","DOI":"10.3390\/jpm15100492"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nrm.2017.87","article-title":"Mechanobiology of YAP and TAZ in physiology and disease","volume":"18","author":"Panciera","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"tkaf029","DOI":"10.1093\/burnst\/tkaf029","article-title":"Organoids\/organs-on-chips towards biomimetic human artificial skin","volume":"13","author":"Huang","year":"2025","journal-title":"Burns Trauma"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"031501","DOI":"10.1063\/5.0275439","article-title":"Mechanobiological engineering strategies for organoid culture","volume":"9","author":"Taghizadeh","year":"2025","journal-title":"APL Bioeng."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Papamichail, L., Koch, L.S., Veerman, D., Broersen, K., and 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. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1515340"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"156065","DOI":"10.1016\/j.metabol.2024.156065","article-title":"Engineering organoids-on-chips for drug testing and evaluation","volume":"162","author":"Wang","year":"2025","journal-title":"Metabolism"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1039\/C7LC00155J","article-title":"Organs-on-chips with integrated electrodes for trans-epithelial electrical resistance (TEER) measurements of human epithelial barrier function","volume":"17","author":"Henry","year":"2017","journal-title":"Lab Chip"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ghane, N., Jafari, R., and Valipour Motlagh, N. (2026). Standardizing TEER Measurements in Blood-Brain Barrier-on-Chip Systems: A Systematic Review of Electrode Designs and Configurations. Biomimetics, 11.","DOI":"10.3390\/biomimetics11020119"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41392-025-02329-1","article-title":"Organ cross-talk: Molecular mechanisms, biological functions, and therapeutic interventions for diseases","volume":"11","author":"Che","year":"2026","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1038\/s41592-024-02549-3","article-title":"Organoids get an upgrade","volume":"21","author":"Mukhopadhyay","year":"2024","journal-title":"Nat. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"191","DOI":"10.14573\/altex.2303261","article-title":"Organoid intelligence (OI)-The ultimate functionality of a brain microphysiological system","volume":"40","author":"Smirnova","year":"2023","journal-title":"ALTEX"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/j.1440-1843.2009.01554.x","article-title":"Respiratory infections: A current and future threat","volume":"14","author":"Waterer","year":"2009","journal-title":"Respirology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101435","DOI":"10.1016\/j.coviro.2024.101435","article-title":"Advancing zoonotic respiratory virus research through the use of organoids","volume":"68\u201369","author":"Flagg","year":"2024","journal-title":"Curr. Opin. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s43556-025-00343-x","article-title":"Organoids in respiratory virus research: Advances and perspectives","volume":"6","author":"Li","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/CMR.00103-20","article-title":"Viral Respiratory Pathogens and Lung Injury","volume":"34","author":"Clementi","year":"2021","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e0194422","DOI":"10.1128\/mbio.01944-22","article-title":"Human Nasal Organoids Model SARS-CoV-2 Upper Respiratory Infection and Recapitulate the Differential Infectivity of Emerging Variants","volume":"13","author":"Chiu","year":"2022","journal-title":"mBio"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e0351121","DOI":"10.1128\/mbio.03511-21","article-title":"The Human Nose Organoid Respiratory Virus Model: An Ex Vivo Human Challenge Model To Study Respiratory Syncytial Virus (RSV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pathogenesis and Evaluate Therapeutics","volume":"13","author":"Rajan","year":"2021","journal-title":"mBio"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6822","DOI":"10.1073\/pnas.1806308115","article-title":"Differentiated human airway organoids to assess infectivity of emerging influenza virus","volume":"115","author":"Zhou","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"106329","DOI":"10.1016\/j.ejps.2022.106329","article-title":"Biomimetic lung-on-a-chip to model virus infection and drug evaluation","volume":"180","author":"Tan","year":"2023","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41551-021-00718-9","article-title":"A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics","volume":"5","author":"Si","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Fisher, C.R., Mba Medie, F., Luu, R.J., Gaibler, R.B., Mulhern, T.J., Miller, C.R., Zhang, C.J., Rubio, L.D., Marr, E.E., and Vijayakumar, V. (2023). A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening. Cells, 12.","DOI":"10.3390\/cells12222639"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chiu, M.C., Zhang, S., Li, C., Liu, X., Yu, Y., Huang, J., Wan, Z., Zhu, X., and Zhou, J. (2023). Apical-Out Human Airway Organoids Modeling SARS-CoV-2 Infection. Viruses, 15.","DOI":"10.3390\/v15051166"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e202402837","DOI":"10.26508\/lsa.202402837","article-title":"Human iPS cell-derived respiratory organoids as a model for respiratory syncytial virus infection","volume":"8","author":"Hashimoto","year":"2025","journal-title":"Life Sci. Alliance"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10772","DOI":"10.1038\/s41467-024-55076-2","article-title":"Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction","volume":"15","author":"Li","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/s41556-021-00721-x","article-title":"Studying SARS-CoV-2 infectivity and therapeutic responses with complex organoids","volume":"23","author":"Chen","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12931-025-03138-4","article-title":"Lung organoids in COPD: Recent advances and future prospects","volume":"26","author":"Huo","year":"2025","journal-title":"Respir. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e100300","DOI":"10.15252\/embj.2018100300","article-title":"Long-term expanding human airway organoids for disease modeling","volume":"38","author":"Sachs","year":"2019","journal-title":"EMBO J."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Steinway, S.N., Saleh, J., Koo, B.K., Delacour, D., and Kim, D.H. (2020). Human Microphysiological Models of Intestinal Tissue and Gut Microbiome. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00725"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1097\/MPG.0000000000002669","article-title":"Acute Gastroenteritis in Children of the World: What Needs to Be Done?","volume":"70","author":"Guarino","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Crawford, S.E., Ramani, S., Blutt, S.E., and Estes, M.K. (2021). Organoids to Dissect Gastrointestinal Virus-Host Interactions: What Have We Learned?. Viruses, 13.","DOI":"10.3390\/v13060999"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e0082024","DOI":"10.1128\/msphere.00820-24","article-title":"Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactions","volume":"10","year":"2025","journal-title":"mSphere"},{"key":"ref_67","first-page":"229\u2013247","article-title":"Human Intestinal Enteroids: New Models to Study Gastrointestinal Virus Infections","volume":"1576","author":"Zou","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1038\/s41598-018-21201-7","article-title":"Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids","volume":"8","author":"Kasendra","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/s41467-020-16491-3","article-title":"Human norovirus targets enteroendocrine epithelial cells in the small intestine","volume":"11","author":"Green","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hagbom, M., Novak, D., Ekstrom, M., Khalid, Y., Andersson, M., Lindh, M., Nordgren, J., and Svensson, L. (2017). Ondansetron treatment reduces rotavirus symptoms-A randomized double-blinded placebo-controlled trial. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186824"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Smith, J.G., Silvestry, M., Lindert, S., Lu, W., Nemerow, G.R., and Stewart, P.L. (2010). Insight into the mechanisms of adenovirus capsid disassembly from studies of defensin neutralization. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000959"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107863","DOI":"10.1016\/j.celrep.2020.107863","article-title":"Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells","volume":"32","author":"Stanifer","year":"2020","journal-title":"Cell Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Depla, J.A., Mulder, L.A., de Sa, R.V., Wartel, M., Sridhar, A., Evers, M.M., Wolthers, K.C., and Pajkrt, D. (2022). Human Brain Organoids as Models for Central Nervous System Viral Infection. Viruses, 14.","DOI":"10.3390\/v14030634"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature12517","article-title":"Cerebral organoids model human brain development and microcephaly","volume":"501","author":"Lancaster","year":"2013","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.stem.2008.09.002","article-title":"Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals","volume":"3","author":"Eiraku","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nbt0509-485a","article-title":"Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling","volume":"27","author":"Chambers","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Su, X., Yue, P., Kong, J., Xu, X., Zhang, Y., Cao, W., Fan, Y., Liu, M., Chen, J., and Liu, A. (2021). Human Brain Organoids as an In Vitro Model System of Viral Infectious Diseases. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.792316"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.stemcr.2021.02.007","article-title":"Neurotropic Effects of SARS-CoV-2 Modeled by the Human Brain Organoids","volume":"16","author":"Ramani","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e0107025","DOI":"10.1128\/jvi.01070-25","article-title":"Human organoids for Risk Group 4 virus research: A new frontier in investigating Nipah virus infection of the central nervous system","volume":"99","author":"Worwa","year":"2025","journal-title":"J. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1242\/dev.140707","article-title":"Using brain organoids to understand Zika virus-induced microcephaly","volume":"144","author":"Qian","year":"2017","journal-title":"Development"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41419-018-0763-y","article-title":"Differential antiviral immunity to Japanese encephalitis virus in developing cortical organoids","volume":"9","author":"Zhang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.stem.2016.02.016","article-title":"Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth","volume":"18","author":"Tang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1016\/j.celrep.2016.08.038","article-title":"Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia","volume":"16","author":"Onorati","year":"2016","journal-title":"Cell Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.aaf6116","article-title":"Zika virus impairs growth in human neurospheres and brain organoids","volume":"352","author":"Garcez","year":"2016","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nature18296","article-title":"The Brazilian Zika virus strain causes birth defects in experimental models","volume":"534","author":"Cugola","year":"2016","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.cell.2016.04.032","article-title":"Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure","volume":"165","author":"Qian","year":"2016","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.stem.2016.12.005","article-title":"Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids","volume":"20","author":"Gabriel","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.stem.2017.07.014","article-title":"Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins","volume":"21","author":"Yoon","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_89","first-page":"10","article-title":"Modeling Herpes Simplex Virus 1 Infections in Human Central Nervous System Neuronal Cells Using Two- and Three-Dimensional Cultures Derived from Induced Pluripotent Stem Cells","volume":"93","author":"Bloom","year":"2019","journal-title":"J. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1016\/j.stem.2021.03.004","article-title":"Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly","volume":"28","author":"Krenn","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"eaay8828","DOI":"10.1126\/sciadv.aay8828","article-title":"A 3D human brain-like tissue model of herpes-induced Alzheimer\u2019s disease","volume":"6","author":"Cairns","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Qiao, H., Guo, M., Shang, J., Zhao, W., Wang, Z., Liu, N., Li, B., Zhou, Y., Wu, Y., and Chen, P. (2020). Herpes simplex virus type 1 infection leads to neurodevelopmental disorder-associated neuropathological changes. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008899"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s13365-023-01133-3","article-title":"iPSC-derived three-dimensional brain organoid models and neurotropic viral infections","volume":"29","author":"Swingler","year":"2023","journal-title":"J. NeuroVirology"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Qiao, H., Zhao, W., Guo, M., Zhu, L., Chen, T., Wang, J., Xu, X., Zhang, Z., Wu, Y., and Chen, P. (2022). Cerebral Organoids for Modeling of HSV-1-Induced-Amyloid beta Associated Neuropathology and Phenotypic Rescue. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115981"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/s41592-019-0586-5","article-title":"Engineering of human brain organoids with a functional vascular-like system","volume":"16","author":"Cakir","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/s41564-023-01405-y","article-title":"Modelling viral encephalitis caused by herpes simplex virus 1 infection in cerebral organoids","volume":"8","author":"Wyler","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"RP87696","DOI":"10.7554\/eLife.87696","article-title":"Rubella virus tropism and single-cell responses in human primary tissue and microglia-containing organoids","volume":"12","author":"Popova","year":"2023","journal-title":"elife"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"103401","DOI":"10.1016\/j.tice.2026.103401","article-title":"Advances in cellular and structural engineering of brain organoids for disease modeling: A Comprehensive Review","volume":"101","author":"Kim","year":"2026","journal-title":"Tissue Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.drudis.2016.06.020","article-title":"Physiologically relevant human tissue models for infectious diseases","volume":"21","author":"Mills","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"R1147","DOI":"10.1016\/j.cub.2017.09.019","article-title":"The liver","volume":"27","author":"Trefts","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"102646","DOI":"10.1016\/j.xcrm.2026.102646","article-title":"Human liver-derived organoids recapitulate Oropouche virus infection and manifestation, enabling antiviral drug discovery","volume":"7","author":"Li","year":"2026","journal-title":"Cell Rep. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1111\/liv.14468","article-title":"The global epidemiology of hepatitis E virus infection: A systematic review and meta-analysis","volume":"40","author":"Li","year":"2020","journal-title":"Liver Int."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1136\/gutjnl-2025-336105","article-title":"iPSC-induced multilineage liver organoids, small intestinal organoids and brain organoids sustain pangenotype hepatitis E virus propagation","volume":"75","author":"Liu","year":"2026","journal-title":"Gut"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"235","DOI":"10.5582\/bst.2026.01043","article-title":"Modeling of the hepatitis B virus life cycle and the efficacy of antivirals in human iPSC-derived hepatic organoids","volume":"20","author":"Liu","year":"2026","journal-title":"Biosci. Trends"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/HEP.0000000000000683","article-title":"A multicellular liver organoid model for investigating hepatitis C virus infection and nonalcoholic fatty liver disease progression","volume":"80","author":"Lee","year":"2024","journal-title":"Hepatology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"8069","DOI":"10.1038\/s41467-025-63323-3","article-title":"Recapitulating dengue virus infection with human pluripotent stem cell-derived liver organoids for antiviral screening","volume":"16","author":"Li","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"110615","DOI":"10.1016\/j.virol.2025.110615","article-title":"Decoding the role of the intestinal epithelium in hepatitis E virus infection using a human organoid prototype of \u201cgut-liver\u201d axis","volume":"610","author":"Liu","year":"2025","journal-title":"Virology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1038\/s41467-024-48910-0","article-title":"Mucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips","volume":"15","author":"Izadifar","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1053\/jfms.2001.0110","article-title":"Ocular manifestations of feline herpesvirus","volume":"3","author":"Andrew","year":"2001","journal-title":"J. Feline Med. Surg."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jtos.2024.11.007","article-title":"Matrix glycosaminoglycans and proteoglycans in human cornea organoids and similarities with fetal corneal stages","volume":"35","author":"Ashworth","year":"2025","journal-title":"Ocul. Surf."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.csbj.2023.01.005","article-title":"Archaic connectivity between the sulfated heparan sulfate and the herpesviruses-An evolutionary potential for cross-species interactions","volume":"21","author":"Elste","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Tiwari, V., Elste, J., Wang, C., and Zhang, F. (2026). Marine Derived Natural Products: Emerging Therapeutics Against Herpes Simplex Virus Infection. Biomolecules, 16.","DOI":"10.3390\/biom16010100"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"124141","DOI":"10.1016\/j.carbpol.2025.124141","article-title":"Marine-derived sulfated glycans display a potent virostatic mechanism to block herpes simplex virus type-1 (HSV-1) entry and spread","volume":"368","author":"Elste","year":"2025","journal-title":"Carbohydr. Polym."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/eye.2017.277","article-title":"Matrix regeneration agents improve wound healing in non-stressed human corneal epithelial cells","volume":"32","author":"Robciuc","year":"2018","journal-title":"Eye"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1242\/jcs.023820","article-title":"The extracellular matrix at a glance","volume":"123","author":"Frantz","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"jcs263574","DOI":"10.1242\/jcs.263574","article-title":"Regulation of cell migration by extracellular matrix mechanics at a glance","volume":"138","author":"Allan","year":"2025","journal-title":"J. Cell Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"102384","DOI":"10.1016\/j.stemcr.2024.11.014","article-title":"Heparan sulfate regulates the fate decisions of human pluripotent stem cells","volume":"20","author":"Syangtan","year":"2025","journal-title":"Stem Cell Rep."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Kaltenbach, D.D., Jaishankar, D., Hao, M., Beer, J.C., Volin, M.V., Desai, U.R., and Tiwari, V. (2018). Sulfotransferase and Heparanase: Remodeling Engines in Promoting Virus Infection and Disease Development. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01315"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"119508","DOI":"10.1016\/j.lfs.2021.119508","article-title":"Antiviral strategies should focus on stimulating the biosynthesis of heparan sulfates, not their inhibition","volume":"277","author":"Cheudjeu","year":"2021","journal-title":"Life Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/978-3-030-34521-1_32","article-title":"Heparanase, Heparan Sulfate and Viral Infection","volume":"1221","author":"Agelidis","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_121","first-page":"144","article-title":"Dynamic hydrogel mechanics in organoid engineering: From matrix design to translational paradigms","volume":"55","author":"Zhang","year":"2026","journal-title":"Bioact. Mater."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/gb-2008-9-5-224","article-title":"Glypicans","volume":"9","author":"Filmus","year":"2008","journal-title":"Genome Biol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Masola, V., Bellin, G., Gambaro, G., and Onisto, M. (2018). Heparanase: A Multitasking Protein Involved in Extracellular Matrix (ECM) Remodeling and Intracellular Events. Cells, 7.","DOI":"10.20944\/preprints201810.0198.v1"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Holm, C., Nguyen, S.N., and Mensah, S.A. (2025). Shear Stress-Dependent Modulation of Endothelin B Receptor: The Role of Endothelial Glycocalyx Heparan Sulfate. Cells, 14.","DOI":"10.3390\/cells14141088"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"A0142","DOI":"10.5702\/massspectrometry.A0142","article-title":"Recent Developments and Application of Mass Spectrometry Imaging in N-Glycosylation Studies: An Overview","volume":"13","author":"Kumar","year":"2024","journal-title":"Mass Spectrom."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1128\/JVI.01718-08","article-title":"Herpesvirus interactions with the host cytoskeleton","volume":"83","author":"Lyman","year":"2009","journal-title":"J. Virol."},{"key":"ref_127","first-page":"67","article-title":"The role of the cytoskeleton during viral infection","volume":"285","author":"Dohner","year":"2005","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Lacin, M.E., and Yildirim, M. (2024). Applications of multiphoton microscopy in imaging cerebral and retinal organoids. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1360482"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.matbio.2025.11.008","article-title":"Human mammary 3D spheroid models uncover the role of filopodia in breaching the basement membrane to facilitate invasion","volume":"143","author":"Corinus","year":"2026","journal-title":"Matrix Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/BCJ20200710","article-title":"Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids","volume":"478","author":"Pinto","year":"2021","journal-title":"Biochem. J."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1089\/ten.teb.2021.0186","article-title":"Extracellular Microenvironmental Control for Organoid Assembly","volume":"28","author":"Sullivan","year":"2022","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(00)04638-9","article-title":"Herpes simplex virus infections","volume":"357","author":"Whitley","year":"2001","journal-title":"Lancet"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Canova, P.N., Charron, A.J., and Leib, D.A. (2024). Models of Herpes Simplex Virus Latency. Viruses, 16.","DOI":"10.3390\/v16050747"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1186\/s13287-021-02651-9","article-title":"Multiocular organoids from human induced pluripotent stem cells displayed retinal, corneal, and retinal pigment epithelium lineages","volume":"12","author":"Veiga","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_135","first-page":"2338","article-title":"Generating minicorneal organoids from human induced pluripotent stem cells","volume":"144","author":"Susaimanickam","year":"2017","journal-title":"Development"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"112247","DOI":"10.1016\/j.isci.2025.112247","article-title":"Erratum: A human cornea-on-a-chip for the study of epithelial wound healing by extracellular vesicles","volume":"28","author":"Yu","year":"2025","journal-title":"iScience"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/s41591-019-0531-2","article-title":"Multiscale reverse engineering of the human ocular surface","volume":"25","author":"Seo","year":"2019","journal-title":"Nat. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jtos.2020.11.004","article-title":"Organoids and organ chips in ophthalmology","volume":"19","author":"Manafi","year":"2021","journal-title":"Ocul. Surf."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41467-022-33114-1","article-title":"Modeling human HSV infection via a vascularized immune-competent skin-on-chip platform","volume":"13","author":"Sun","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1080\/17425255.2021.1908996","article-title":"Multi-organ-on-a-chip for pharmacokinetics and toxicokinetic study of drugs","volume":"17","author":"Sung","year":"2021","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"200","DOI":"10.2174\/1574886313666180619120406","article-title":"Off-Label Use of Drugs and Adverse Drug Reactions in Pediatric Units: A Prospective, Multicenter Study","volume":"13","author":"Pratico","year":"2018","journal-title":"Curr. Drug Saf."},{"key":"ref_142","first-page":"382","article-title":"Off-label antineoplastic drugs. An effectiveness and safety study","volume":"41","year":"2017","journal-title":"Farm. Hosp."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Skardal, A. (2024). Grand challenges in organoid and organ-on-a-chip technologies. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1366280"},{"key":"ref_144","first-page":"e62857","article-title":"Adapting Gastrointestinal Organoids for Pathogen Infection and Single Cell Sequencing under Biosafety Level 3 (BSL-3) Conditions","volume":"175","author":"Stanifer","year":"2021","journal-title":"J. Vis. Exp."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"102316","DOI":"10.1016\/j.mtbio.2025.102316","article-title":"Simple and high-containment lung-on-chip model for studying respiratory viral infections using human primary lung cells","volume":"35","author":"Barata","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"30582","DOI":"10.1038\/s41598-025-15846-4","article-title":"Integration of biomimetic organoid-on-chip and 2D models advances the mechanistic Understanding of STEAP3-mediated regulation in intestinal viral infection","volume":"15","author":"Chen","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"20417314241232502","DOI":"10.1177\/20417314241232502","article-title":"Advanced lung organoids for respiratory system and pulmonary disease modeling","volume":"15","author":"Joo","year":"2024","journal-title":"J. Tissue Eng."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"vlaf075","DOI":"10.1093\/immhor\/vlaf075","article-title":"Screening for next generation vaccines in human immune organoids","volume":"9","author":"Chen","year":"2025","journal-title":"ImmunoHorizons"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Bonaiti, E., Muraro, M.G., Robert, P.A., Jakscha, J., Dirnhofer, S., Martin, I., and Berger, C.T. (2024). Tonsil explants as a human in vitro model to study vaccine responses. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1425455"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"5118","DOI":"10.1038\/s41467-024-48864-3","article-title":"Roadblocks confronting widespread dissemination and deployment of Organs on Chips","volume":"15","author":"Alver","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s44385-025-00054-6","article-title":"From organoid culture to manufacturing: Technologies for reproducible and scalable organoid production","volume":"3","author":"Kim","year":"2026","journal-title":"npj Biomed. Innov."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/17\/1514\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:14:28Z","timestamp":1787818468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/17\/1514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":151,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cells15171514"],"URL":"https:\/\/doi.org\/10.3390\/cells15171514","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]}}}