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dc.contributor.authorOffeddu, Giovanni
dc.contributor.authorHaase, Kristina Michelle
dc.contributor.authorGillrie, Mark Robert
dc.contributor.authorLi, Ran
dc.contributor.authorMorozova, Olga
dc.contributor.authorHickman, Dean
dc.contributor.authorKnutson, Charles G.
dc.contributor.authorKamm, Roger Dale
dc.date.accessioned2020-10-29T22:37:39Z
dc.date.available2020-10-29T22:37:39Z
dc.date.issued2019-08
dc.date.submitted2019-04
dc.identifier.issn0142-9612
dc.identifier.urihttps://hdl.handle.net/1721.1/128263
dc.description.abstractRecent therapeutic success of large-molecule biologics has led to intense interest in assays to measure with precision their transport across the vascular endothelium and into the target tissue. Most current in vitro endothelial models show unrealistically large permeability coefficients due to a non-physiological paracellular transport. Thus, more advanced systems are required to better recapitulate and discern the important contribution of transcellular transport (transcytosis), particularly of pharmaceutically-relevant proteins. Here, a robust platform technology for the measurement of transport through a human endothelium is presented, which utilizes in vitro microvascular networks (MVNs). The self-assembled MVNs recapitulate the morphology and junctional complexity of in vivo capillaries, and express key endothelial vesicular transport proteins. This results in measured permeabilities to large molecules comparable to those observed in vivo, which are orders of magnitude lower than those measured in transwells. The permeability of albumin and immunoglobulin G (IgG), biopharmaceutically-relevant proteins, is shown to occur primarily via transcytosis, with passage of IgG regulated by the receptor FcRn. The physiological relevance of the MVNs make it a valuable tool to assess the distribution of biopharmaceuticals into tissues, and may be used to prioritize candidate molecules from this increasingly important class of therapeutics.en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.biomaterials.2019.05.022en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceProf. Kamm via Elizabeth Soergelen_US
dc.titleAn on-chip model of protein paracellular and transcellular permeability in the microcirculationen_US
dc.typeArticleen_US
dc.identifier.citationOffeddu, Giovanni S. et al. "An on-chip model of protein paracellular and transcellular permeability in the microcirculation." Biomaterials 212 (August 2019): 115-125 © 2019 Elsevier Ltden_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mechanical Engineeringen_US
dc.relation.journalBiomaterialsen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2020-10-28T17:56:14Z
dspace.orderedauthorsOffeddu, GS; Haase, K; Gillrie, MR; Li, R; Morozova, O; Hickman, D; Knutson, CG; Kamm, RDen_US
dspace.date.submission2020-10-28T17:56:28Z
mit.journal.volume212en_US
mit.licensePUBLISHER_CC


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