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Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology.
- Source :
-
Journal of the mechanical behavior of biomedical materials [J Mech Behav Biomed Mater] 2015 Mar; Vol. 55, pp. 87-103. Date of Electronic Publication: 2015 Oct 30. - Publication Year :
- 2015
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Abstract
- Tissue engineering and cell based liver therapies have utilized primary hepatocytes with limited success due to the failure of hepatocytes to maintain their phenotype in vitro. In order to overcome this challenge, hyaluronic acid (HA) cell culture substrates were formulated to closely mimic the composition and stiffness of the normal liver cellular microenvironment. The stiffness of the substrate was modulated by adjusting HA hydrogel crosslinking. Additionally, the repertoire of bioactive molecules within the HA substrate was bolstered by supplementation with normal liver extracellular matrix (ECM). Primary human hepatocyte viability and phenotype were determined over a narrow physiologically relevant range of substrate stiffnesses from 600 to 4600Pa in both the presence and absence of liver ECM. Cell attachment, viability, and organization of the actin cytoskeleton improved with increased stiffness up to 4600Pa. These differences were not evident in earlier time points or substrates containing only HA. However, gene expression for the hepatocyte markers hepatocyte nuclear factor 4 alpha (HNF4α) and albumin significantly decreased on the 4600Pa stiffness at day 7 indicating that cells may not have maintained their phenotype long-term at this stiffness. Function, as measured by albumin secretion, varied with both stiffness and time in culture and peaked at day 7 at the 1200Pa stiffness, slightly below the stiffness of normal liver ECM at 3000Pa. Overall, gel stiffness affected primary human hepatocyte cell adhesion, functional marker expression, and morphological characteristics dependent on both the presence of liver ECM in gel substrates and time in culture.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Biocompatible Materials chemistry
Biocompatible Materials pharmacology
Biomarkers metabolism
Cell Adhesion drug effects
Cell Survival drug effects
Cell Transplantation
Cytoplasm drug effects
Cytoplasm enzymology
Gene Expression Regulation drug effects
Glycosaminoglycans metabolism
Hepatocytes drug effects
Hepatocytes metabolism
Humans
Hydrogels chemistry
Protein Kinases metabolism
Rats
Solubility
rho GTP-Binding Proteins metabolism
Extracellular Matrix metabolism
Hepatocytes cytology
Hyaluronic Acid chemistry
Hyaluronic Acid pharmacology
Liver cytology
Mechanical Phenomena
Tissue Engineering
Subjects
Details
- Language :
- English
- ISSN :
- 1878-0180
- Volume :
- 55
- Database :
- MEDLINE
- Journal :
- Journal of the mechanical behavior of biomedical materials
- Publication Type :
- Academic Journal
- Accession number :
- 26569044
- Full Text :
- https://doi.org/10.1016/j.jmbbm.2015.10.016