{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T17:39:27Z","timestamp":1771954767662,"version":"3.50.1"},"reference-count":113,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["2022.06174.PTDC"],"award-info":[{"award-number":["2022.06174.PTDC"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UID\/QUI\/00313\/2020"],"award-info":[{"award-number":["UID\/QUI\/00313\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["PT0051.B.04.C"],"award-info":[{"award-number":["PT0051.B.04.C"]}]},{"name":"Coimbra Chemistry Centre","award":["2022.06174.PTDC"],"award-info":[{"award-number":["2022.06174.PTDC"]}]},{"name":"Coimbra Chemistry Centre","award":["UID\/QUI\/00313\/2020"],"award-info":[{"award-number":["UID\/QUI\/00313\/2020"]}]},{"name":"Coimbra Chemistry Centre","award":["PT0051.B.04.C"],"award-info":[{"award-number":["PT0051.B.04.C"]}]},{"name":"Santander Universidades","award":["2022.06174.PTDC"],"award-info":[{"award-number":["2022.06174.PTDC"]}]},{"name":"Santander Universidades","award":["UID\/QUI\/00313\/2020"],"award-info":[{"award-number":["UID\/QUI\/00313\/2020"]}]},{"name":"Santander Universidades","award":["PT0051.B.04.C"],"award-info":[{"award-number":["PT0051.B.04.C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>This review outlines the evolutionary journey from traditional two-dimensional (2D) cell culture to the revolutionary field of organ-on-a-chip technology. Organ-on-a-chip technology integrates microfluidic systems to mimic the complex physiological environments of human organs, surpassing the limitations of conventional 2D cultures. This evolution has opened new possibilities for understanding cell\u2013cell interactions, cellular responses, drug screening, and disease modeling. However, the design and manufacture of microchips significantly influence their functionality, reliability, and applicability to different biomedical applications. Therefore, it is important to carefully consider design parameters, including the number of channels (single, double, or multi-channels), the channel shape, and the biological context. Simultaneously, the selection of appropriate materials compatible with the cells and fabrication methods optimize the chips\u2019 capabilities for specific applications, mitigating some disadvantages associated with these systems. Furthermore, the success of organ-on-a-chip platforms greatly depends on the careful selection and utilization of cell resources. Advances in stem cell technology and tissue engineering have contributed to the availability of diverse cell sources, facilitating the development of more accurate and reliable organ-on-a-chip models. In conclusion, a holistic perspective of in vitro cellular modeling is provided, highlighting the integration of microfluidic technology and meticulous chip design, which play a pivotal role in replicating organ-specific microenvironments. At the same time, the sensible use of cell resources ensures the fidelity and applicability of these innovative platforms in several biomedical applications.<\/jats:p>","DOI":"10.3390\/pharmaceutics16050615","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T07:04:14Z","timestamp":1714633454000},"page":"615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Organ-on-a-Chip: Ubi sumus? Fundamentals and Design Aspects"],"prefix":"10.3390","volume":"16","author":[{"given":"Ana Sofia","family":"Morais","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-4517","authenticated-orcid":false,"given":"Maria","family":"Mendes","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Chemistry Centre, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9644-6282","authenticated-orcid":false,"given":"Marta Agostinho","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Chemistry Centre, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9718-8035","authenticated-orcid":false,"given":"Jo\u00e3o J.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Chemistry Centre, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6725-6460","authenticated-orcid":false,"given":"Alberto Canelas","family":"Pais","sequence":"additional","affiliation":[{"name":"Coimbra Chemistry Centre, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"given":"Silvia M.","family":"Mih\u0103il\u0103","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3508 TB Utrecht, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3424-548X","authenticated-orcid":false,"given":"Carla","family":"Vitorino","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Chemistry Centre, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jensen, C., and Teng, Y. 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