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The development of a cell\u2010expansion process with adherent cells is challenging as scale\u2010up requires the expansion of the cell culture surface. Microcarrier (MC)\u2010based cultures are still predominate. However, the development of MC processes from scratch possesses particular challenges due to their complexity. A novel approach for the reduction of development times and costs of cell propagation processes is the combination of mathematical process models with statistical optimization methods, called model\u2010assisted Design of Experiments (mDoE). In this study, an mDoE workflow was evaluated successfully for the design of a MC\u2010based expansion process of adherent L929 cells at a very early stage of development with limited prior knowledge. At the start, the analytical methods and the screening of appropriate MCs were evaluated. Then, cause\u2010effect relationships (e.g., cell growth related to medium conditions) were worked out, and a mathematical process model was set\u2010up and adapted to experimental data for modeling purposes. The model was subsequently used in mDoE to identify optimized process conditions, which were proven experimentally. An eight\u2010fold increase in cell yield was achieved basically by reducing the initial MC concentration.<\/jats:p>","DOI":"10.1002\/elsc.202200059","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T08:14:37Z","timestamp":1682410477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design of cell expansion processes for adherent\u2010growing cells with mDoE\u2010workflow"],"prefix":"10.1002","volume":"23","author":[{"given":"Kim B.","family":"Kuchem\u00fcller","sequence":"first","affiliation":[{"name":"Bioprocess and Biosystems Engineering Hamburg University of Technology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-9718","authenticated-orcid":false,"given":"Ralf","family":"P\u00f6rtner","sequence":"additional","affiliation":[{"name":"Bioprocess and Biosystems Engineering Hamburg University of Technology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9546-055X","authenticated-orcid":false,"given":"Johannes","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Bioprocess and Biosystems Engineering Hamburg University of Technology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0040"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.14740\/jocmr3964"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809992"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.11.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2020.575146"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/pr9030447"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4760414"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-399-8_5"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-019-02738-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2019.109782"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2015.02.003"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-021-01463-y"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00449-019-02089-7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00449-020-02478-3"},{"key":"e_1_2_9_16_1","first-page":"473","article-title":"Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors","volume":"1","author":"Rafiq QA","year":"2015","journal-title":"Biotechnol J"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2144\/000114568"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(98)00011-8"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-011-9359-4"},{"key":"e_1_2_9_20_1","first-page":"1","volume-title":"Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology","author":"Merten O\u2010W","year":"2009"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbt.2012.05.021"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp0701923"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp020035y"},{"key":"#cr-split#-e_1_2_9_24_1.1","unstructured":"GE Healthcare Bio\u2010Sciences AB.Microcarrier Cell Culture: Principles and Methods [Internet] GE Healthcare Bio\u2010Sciences AB 2013[modified 2013"},{"key":"#cr-split#-e_1_2_9_24_1.2","unstructured":"cited 2019 Feb 28]. 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