Mimicking Physiologically Relevant Hepatocyte Zonation Using Immunomodulatory Silk Liver Extracellular Matrix Scaffolds toward a Bioartificial Liver Platform

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:ACS applied materials & interfaces 2021-06, Vol.13 (21), p.24401-24421
Hauptverfasser: Janani, G, Mandal, Biman B
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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 and drug screening.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.1c00719