{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:24:28Z","timestamp":1787574268122,"version":"build-2736575974"},"reference-count":182,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>\n                    Two\u2013dimensional (2D) cell cultures have been used as\n                    <jats:italic>in vitro<\/jats:italic>\n                    models in biomedical research as fundamental tools for investigating biological processes. However, their limited capacity to recapitulate the complexity of human tissues has driven the search for more physiologically relevant\n                    <jats:italic>in vitro<\/jats:italic>\n                    systems. In parallel, limitations in the predictive capacity, costs, and ethical concerns associated with animal models have reinforced the importance of the 3Rs principles (Replacement, Reduction, and Refinement), introduced in 1959, and more recently contributed to the emergence of New Approach Methodologies (NAMs). In this context, three\u2013dimensional (3D) cell culture models, such as spheroids, organoids, and bioprinted models have been developed. This literature review focuses on studies that directly compare spheroids, organoids, and 3D\u2013printed models with their 2D culture counterparts, highlighting their potential and limitations as human\u2013relevant NAMs.\n                  <\/jats:p>","DOI":"10.3389\/fbioe.2026.1862040","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:27Z","timestamp":1787572047000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond monolayers: a comparative analysis of 2D cell cultures and 3D in vitro models as new approach methodologies"],"prefix":"10.3389","volume":"14","author":[{"given":"Italo Rodrigo","family":"Calori","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Basic Science and Translational Research, The University of Texas Medical Branch at Galveston","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula Pereira","family":"Guimaraes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Basic Science and Translational Research, The University of Texas Medical Branch at Galveston","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananth Kumar","family":"Kammala","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Basic Science and Translational Research, The University of Texas Medical Branch at Galveston","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren S.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Basic Science and Translational Research, The University of Texas Medical Branch at Galveston","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramkumar","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Basic Science and Translational Research, The University of Texas Medical Branch at Galveston","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3690","DOI":"10.1039\/c4lc00479e","article-title":"Rapid and high-throughput formation of 3D embryoid bodies in hydrogels using the dielectrophoresis technique","volume":"14","author":"Ahadian","year":"2014","journal-title":"Lab Chip"},{"key":"B2","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s11814-022-1327-5","article-title":"Microfabrication methods for 3D spheroids formation and their application in biomedical engineering","volume":"40","author":"Ahn","year":"2023","journal-title":"Korean J. 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