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Development of scaffolds with adjusted stiffness for mimicking disease-related alterations of liver rigidity

  • Drug-induced liver toxicity is one of the most common reasons for the failure of drugs in clinical trials and frequent withdrawal from the market. Reasons for such failures include the low predictive power of in vivo studies, that is mainly caused by metabolic differences between humans and animals, and intraspecific variances. In addition to factors such as age and genetic background, changes in drug metabolism can also be caused by disease-related changes in the liver. Such metabolic changes have also been observed in clinical settings, for example, in association with a change in liver stiffness, a major characteristic of an altered fibrotic liver. For mimicking these changes in an in vitro model, this study aimed to develop scaffolds that represent the rigidity of healthy and fibrotic liver tissue. We observed that liver cells plated on scaffolds representing the stiffness of healthy livers showed a higher metabolic activity compared to cells plated on stiffer scaffolds. Additionally, we detected a positive effect of a scaffold pre-coated with fetal calf serum (FCS)-containing media. This pre-incubation resulted in increased cell adherence during cell seeding onto the scaffolds. In summary, we developed a scaffold-based 3D model that mimics liver stiffness-dependent changes in drug metabolism that may more easily predict drug interaction in diseased livers.

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Metadaten
Author of HS ReutlingenWeimer, Marina; Athanasopulu, Kiriaki; Kemkemer, Ralf
URN:urn:nbn:de:bsz:rt2-opus4-30134
DOI:https://doi.org/10.3390/jfb11010017
ISSN:2079-4983
Erschienen in:Journal of functional biomaterials
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Year of Publication:2020
Tag:Arg-Gly-Asp (RGD)-peptides; cell attachment; in vitro model; pre-coating; scaffold culture; stiffness
Volume:11
Issue:1
Page Number:19
First Page:1
Last Page:19
Article Number:17
DDC classes:570 Biowissenschaften, Biologie
Open Access?:Ja
Licence (German):License Logo  Creative Commons - CC BY - Namensnennung 4.0 International