Mimicking physiologically relevant hepatocyte zonation using immunomodulatory silk liver extracellular matrix scaffolds toward a bioartificial liver platform
Abstract
Mimicking nativelike metabolic zonation is indispensable to develop an efficient bioartificial liver model, as it facilitates physiological cues, hepatocyte polarity, and phenotypic functions. The present study shows the first evidence of hepatocyte metabolic heterogeneity in an in vitro liver model encompassing liver extracellular matrix (ECM)-functionalized silk scaffolds (LECM-SF) by altering ECM proportion. Upon static culture, individual LECM-SF scaffold supports differential synthetic and metabolic functions of cultured primary neonatal rat hepatocytes (PNRHs), owing to discrete biophysical attributes. A single in vitro liver system comprising PNRHs seeded LECM-SF scaffolds assisting periportal to pericentral gradient functions is stacked and matured in a perfusion bioreactor to simulate oxygen gradient. The scaffold with high ECM supports periportal-specific albumin synthesis, urea secretion, and bile duct formation, albeit scaffold with low ECM supports pericentral-specific cytochrome P450 activity. Extensive physicochemical characterizations confirmed the stability and interconnected porous network of scaffolds, signifying cellular infiltration and bidirectional nutrient diffusion. Furthermore, scaffolds demonstrate minimal thrombogenicity, reduced foreign-body response, and enhanced pro-remodeling macrophage activation, supporting constructive tissue remodeling. The developed liver model with zone-specific functions would be a promising avenue in bioartificial liver…
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Physiological relevant in vitro models provide a promising platform for modelling the physiochemical conditions of the hepatic microenvironment.
“Physiological relevant in vitro models provide a promising platform for modelling the physiochemical conditions of the hepatic microenvironment (Janani and Mandal, 2021;Kostrzewski et al., 2021;Paradiso et al., 2023).”
From Fast formation and maturation enhancement of human liver organoids using a liver-organoid-on-a-chip (2024) · cites this paper as Janani and Mandal, 2021
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- Authors
- Janani, G., & Mandal, B. B.
- Affiliations
- Indian Institute of Technology Guwahati (IN)
- Corresponding author
- Mandal, Biman B.
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-05-21
- Volume
- 13
- Issue
- 21
- Pages
- 24401-24421
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W3160678358
- Cited by
- 31
- References
- 46
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 7 · 2022: 10 · 2021: 2
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Biotechnology , Ministry of Science and Technology
- Department of Science and Technology, Ministry of Science and Technology
- Topics
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- hepatocyte zonation, bioartificial liver, silk fibroin scaffolds, liver extracellular matrix, albumin synthesis, urea secretion, bile duct formation, cytochrome P450 activity, perfusion bioreactor, oxygen gradients, thrombogenicity, macrophage activation, tissue remodeling, drug screening
- MeSH terms
- Adjuvants, Immunologic, Animals, Animals, Newborn, Artificial Organs, Extracellular Matrix, Liver, Molecular Mimicry, Hepatocytes, Silk, Rats
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