{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:49:12Z","timestamp":1790092152059,"version":"4.0.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"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>The eukaryotic cell-based biomedicine landscape is undergoing a paradigm shift, driven by the transition from static culture to highly controlled microbioreactor environments. This mini-review assembles high-value applications, including autologous cell therapies, recombinant protein production, induced pluripotent stem cell expansion, and organoid engineering. Technologically, we highlight how the integration of microfluidics into Chimeric antigen receptor T-cell manufacturing achieves numerical optimization of cell count and phenotypic distribution through automated, closed-loop workflows. Regarding bioproduction, perfusion-based microbioreactors demonstrate a six-fold increase in productivity over traditional T-flasks, utilizing at-line monitoring and advanced cell-retention configurations to minimize shear-induced damage. Beyond production, these systems are active regulators of oxygenation and tissue morphogenesis in the context of human induced pluripotent stem cells while enabling controlled 3D tissue organization. In this connection, microfluidic platforms influence extracellular matrix remodeling and developmental signaling by modulating convective flow and mechanotransduction pathways. Furthermore, automation enhances reproducibility in feeding schedules and differentiation timing. Critical to this endeavor, the ability to generate precise spatiotemporal morphogen gradients enables reproducible lineage commitment and the maturation of complex tissues through synchronized mechanical and electrical stimuli for hosting organoid growth. The microbioreactor\u2019s superior mass transfer and low shear stress produced organoids 140% larger than static controls. While automation significantly reduces reagent consumption and inter-batch variability, challenges in scalability and material selection remain. Finally, parameters that push the microscale control boundaries are presented. Collectively, these advancements streamline therapeutic pipelines, support the replacement of animal-based testing, and align with Sustainable Development Goal 3 by accelerating the move toward personalized medicine and ethical drug screening.<\/jats:p>","DOI":"10.3389\/fbioe.2026.1854988","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:34:04Z","timestamp":1783920844000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Microbioreactor design for eukaryotic cell-based biomedical applications"],"prefix":"10.3389","volume":"14","author":[{"given":"Gustavo","family":"Rosero","sequence":"first","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Ingenier\u00eda e Industrias, Ingenier\u00eda Civil, Mec\u00e1nica Computacional e Inteligencia Artificial Aplicada (MCIAA)","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"P\u00e9rez-Sosa","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica (CENBIO), Universidad UTE, Facultad de Ciencias de La Salud Eugenio Espejo","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio Patricio","family":"Pe\u00f1aherrera","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00edas Aplicadas y Desarrollo Industrial, Universidad Internacional Del Ecuador UIDE","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Belen","family":"Pe\u00f1aherrera-Pazmi\u00f1o","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica (CENBIO), Universidad UTE, Facultad de Ciencias de La Salud Eugenio Espejo","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/978-1-0716-1246-0_5","article-title":"Use of transparent liquid marble: microbioreactor to culture cardiospheres","volume":"2273","author":"Aalders","year":"2021","journal-title":"Methods Mol. 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