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Shear stress and mass transfer have always been the vital operating parameters for the bioreactor in creating a suitable microenvironment for cell growth and antibody production. However, researchers have not actively focused on the rheology of CHO cell suspensions and its impact on these parameters in bioreactors. The factors influencing the rheology of suspensions were first investigated in this study. The findings demonstrated that the shear\u2010thinning behavior of the suspension was primarily affected by the cell volume fraction (<jats:italic>\u03a6<\/jats:italic>). As <jats:italic>\u03a6<\/jats:italic> increases, the shear\u2010thinning behavior gradually weakened, and the viscosity increased. The Sisko model was used to characterize rheology, while computational fluid dynamics simulations evaluated its impact on bioreactor performance. The simulation results revealed that the rheology of the suspensions caused a multiple increase in shear stress and a 10%\u201340% decrease in the volumetric mass transfer coefficient (kLa) in the bioreactor. Therefore, the effects of rheology cannot be ignored while designing operating parameters. This study established empirical correlations among Pg\/V, Vg, <jats:italic>\u03a6<\/jats:italic>, and kLa, thus delivering guidance for selecting appropriate operating parameters in high\u2010density and ultra\u2010high\u2010density cell cultivation processes. The findings provide a scientific foundation for optimizing CHO cell cultivation processes and quantifying suitable microenvironment parameters for cell growth and production. They also offer novel ideas and strategies for scaling up and optimizing the structural parameters of bioreactors.<\/jats:p>","DOI":"10.1002\/biot.70003","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T11:35:52Z","timestamp":1742297752000},"source":"Crossref","is-referenced-by-count":4,"title":["Rheology of CHO Cell Suspensions and Its Effects on High\u2010Density Cultivation Process and Bioreactor Design"],"prefix":"10.1002","volume":"20","author":[{"given":"Botao","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyuan","family":"Ran","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijian","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gance","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8077-3617","authenticated-orcid":false,"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9310-1553","authenticated-orcid":false,"given":"Qian","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Song","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mec.2024.e00232"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/pr12040806"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-024-01060-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.3264"},{"key":"e_1_2_8_6_1","unstructured":"B.Madsen J.Cobia andN.Jones \u201cContinuous Process Performance Enhancements for 50 to 500 L Single\u2010Use Bioreactors: A Technical Comparison of Performance Characterization Cell Culture and Scale\u2010Up Modeling \u201d inConference on Single\u2010Use Technologies II: Bridging Polymer Science to Biotechnology Applications(2019) 96."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.22356"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26723"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2004.10.006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cherd.2023.04.066"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2020.107870"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3233\/BIR-1979-16303"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm401335g"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm501481y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnnfm.2020.104298"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1017\/jfm.2019.393"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00397-015-0882-7"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1SM01299A"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.110.078305"},{"key":"e_1_2_8_20_1","first-page":"45","volume-title":"Biomedical and Health Research\u2010Commission of the European Communities Then IOS Press","author":"Cokelet G. 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