Microfluidic human physiomimetic liver model as a screening platform for drug induced liver injury.

Autor: Dey S; Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India., Bhat A; Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India., Janani G; Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India., Shandilya V; Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India., Gupta R; Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India; Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India; Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India., Mandal BB; Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India; Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India; Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India. Electronic address: biman.mandal@iitg.ac.in.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2024 Oct; Vol. 310, pp. 122627. Date of Electronic Publication: 2024 May 21.
DOI: 10.1016/j.biomaterials.2024.122627
Abstrakt: The pre-clinical animal models often fail to predict intrinsic and idiosyncratic drug induced liver injury (DILI), thus contributing to drug failures in clinical trials, black box warnings and withdrawal of marketed drugs. This suggests a critical need for human-relevant in vitro models to predict diverse DILI phenotypes. In this study, a porcine liver extracellular matrix (ECM) based biomaterial ink with high printing fidelity, biocompatibility and tunable rheological and mechanical properties is formulated for supporting both parenchymal and non-parenchymal cells. Further, we applied 3D printing and microfluidic technology to bioengineer a human physiomimetic liver acinus model (HPLAM), recapitulating the radial hepatic cord-like structure with functional sinusoidal microvasculature network, biochemical and biophysical properties of native liver acinus. Intriguingly, the human derived hepatic cells incorporated HPLAM cultured under physiologically relevant microenvironment, acts as metabolic biofactories manifesting enhanced hepatic functionality, secretome levels and biomarkers expression over several weeks. We also report that the matured HPLAM reproduces dose- and time-dependent hepatotoxic response of human clinical relevance to drugs typically recognized for inducing diverse DILI phenotypes as compared to conventional static culture. Overall, the developed HPLAM emulates in vivo like functions and may provide a useful platform for DILI risk assessment to better determine safety and human risk.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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