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dc.contributor.authorLin, Christine
dc.contributor.authorRomero, Raimundo
dc.contributor.authorSorokina, Lioudmila, V.
dc.contributor.authorBallinger, Kimberly, R.
dc.contributor.authorPlace, Laura, W.
dc.contributor.authorKipper, Matt, J.
dc.contributor.authorKhetani, Salman, R.
dc.date.accessioned2018-06-25T19:20:43Z
dc.date.available2018-06-25T19:20:43Z
dc.date.issued2017-11-15
dc.identifier.issn1549-3296
dc.identifier.other10.1002/jbm.a.36293
dc.identifier.urihttp://hdl.handle.net/10027/22422
dc.descriptionThis is the pre-peer reviewed version of the following article: Lin, C., Romero, R., Sorokina, L. V., Ballinger, K. R., Place, L. W., Kipper, M. J. and Khetani, S. R. A polyelectrolyte multilayer platform for investigating growth factor delivery modes in human liver cultures. Journal of Biomedical Materials Research Part A. 2018. 106(4): 971-984, which has been published in final form at 10.1002/jbm.a.36293..en_US
dc.description.abstractPolyelectrolyte multilayers (PEMs) of chitosan and heparin are useful for mimicking growth factor (GF) binding to extracellular matrix (ECM) as in vivo. Here, we developed a PEM platform for delivering bound/adsorbed GFs to monocultures of primary human hepatocytes (PHHs) and PHH/non-parenchymal cell (NPC) co-cultures, which are useful for drug development and regenerative medicine. The effects of ECM protein coating (collagen I, fibronectin, and Matrigel®) and terminal PEM layer on PHH attachment/functions were determined. Then, heparin-terminated/fibronectin-coated PEMs were used to deliver varying concentrations of an adsorbed model GF, transforming growth factor β (TGFβ), to PHH monocultures while using soluble TGFβ delivery via culture medium as the conventional control. Soluble TGFβ delivery caused a severe, monotonic, and sustained downregulation of all PHH functions measured (albumin and urea secretions, cytochrome-P450 2A6 and 3A4 enzyme activities), whereas adsorbed TGFβ delivery caused transient upregulation of 3 out of 4 functions. Finally, functionally stable co-cultures of PHHs and 3T3-J2 murine embryonic fibroblasts were created on the heparin-terminated/fibronectin-coated PEMs modified with adsorbed TGFβ to elucidate similarities and differences in functional response relative to the monocultures. In conclusion, chitosan-heparin PEMs constitute a robust platform for investigating the effects of GF delivery modes on PHH monocultures and PHH/NPC co-cultures.en_US
dc.description.sponsorshipThis work was supported by Colorado State University, NSF (CAREER award CBET-1351909 to S.R.K. and DBI-1531921 to M.J.K.), and NIH (1R03EB019184-01 to S.R.K.).en_US
dc.language.isoen_USen_US
dc.publisherWileyen_US
dc.subjectfibroblastsen_US
dc.subjectco-culturesen_US
dc.subjecthepatocytesen_US
dc.titleA polyelectrolyte multilayer platform for investigating growth factor delivery modes in human liver culturesen_US
dc.typeArticleen_US
dc.identifier.citationLin, C., Romero, R., Sorokina, L. V., Ballinger, K. R., Place, L. W., Kipper, M. J. and Khetani, S. R. A polyelectrolyte multilayer platform for investigating growth factor delivery modes in human liver cultures. Journal of Biomedical Materials Research Part A. 2018. 106(4): 971-984. 10.1002/jbm.a.36293en_US


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