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Biosys."],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Poor oxygen transport is a major obstacle currently for 3D microtissue culture platforms, which at this time cannot be grown large enough to be truly physiologically relevant and replicate adult human organ functions. To overcome internal oxygen transport deficiencies, oxygenating microgels are formed utilizing perfluorocarbon (PFC) modified chitosan and a highly scalable water\u2010in\u2010oil miniemulsion method. Microgels that are on the order of a cell diameter (\u224810 \u00b5m) are formed allowing them to directly associate with cells when included in 3D spheroid culture, while not being internalized. The presence of immobilized PFCs in these microgels allows for enhancement and tuning of oxygen transport when incorporated into cultured microtissues. As such, it is demonstrated that incorporating oxygenating microgels at ratios ranging from 50:1 to 400:1 (# of cells:# of microgels) into dense human fibroblast\u2010based spheroids facilitated the growth of larger human cell\u2010based spheroids, especially at the highest incorporation percentages (50:1), which lacked defined hypoxic cores. Quantification of total double\u2010stranded (ds)\u2010DNA, a measure of number of live cells, demonstrated similar results to hypoxia quantification, showing more ds\u2010DNA due incorporation of oxygenating microgels. Finally, oxygen concentrations are measured at different depths within spheroids directly and confirmed higher oxygen partial pressures due to chitosan\u2010PFC microspheres.<\/jats:p>","DOI":"10.1002\/adbi.201900250","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T06:26:13Z","timestamp":1595226373000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Fluorinated Chitosan Microgels to Overcome Internal Oxygen Transport Deficiencies in Microtissue Culture Systems"],"prefix":"10.1002","volume":"4","author":[{"given":"Pritam S.","family":"Patil","sequence":"first","affiliation":[{"name":"Department of Chemical, Biomolecular, and Corrosion Engineering Whitby Hall University of Akron  Akron OH 44325\u20103906 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Mansouri","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biomolecular, and Corrosion Engineering Whitby Hall University of Akron  Akron OH 44325\u20103906 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6356-7691","authenticated-orcid":false,"given":"Nic D.","family":"Leipzig","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biomolecular, and Corrosion Engineering Whitby Hall University of Akron  Akron OH 44325\u20103906 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,7,19]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2007.124537"},{"key":"e_1_2_7_2_1","unstructured":"US Food and Drug Administration https:\/\/www.fda.gov\/ForPatients\/Approvals\/Drugs\/default.htm(accessed: September 2019)."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2015.27"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057117696795"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2014.02.006"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2012.12.003"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(79)90953-2"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2017.11.012"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1081\/BIO-200046659"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2010.08.013"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.35"},{"key":"e_1_2_7_10_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(98)01205-0"},{"key":"e_1_2_7_10_4","doi-asserted-by":"publisher","DOI":"10.1007\/s00449-014-1143-3"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.34052"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1039\/c4ra01502a"},{"key":"e_1_2_7_11_3","doi-asserted-by":"publisher","DOI":"10.1007\/s10856-014-5223-3"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2012.10.034"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.36079"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-013-0925-0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.03.022"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0203371"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2018.0887"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom9090470"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.9b00833"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2020.110656"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2010.02.003"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2012.02.018"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5LC00785B"},{"key":"e_1_2_7_22_1","first-page":"990","volume":"80","author":"Paul B. 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