Extracellular Matrix Optimization for Enhanced Physiological Relevance in Hepatic Tissue-Chips.

Abdul Rahim Chethikkattuveli Salih,Arun Asif,Kyung Hyun Choi,Afaque Manzoor Soomro,Young Su Kim,Kinam Hyun,Jae Wook Lee,Dongeun Huh,Hafiz Muhammad Umer Farooqi,Kyung Hwan Kim

doi:10.3390/polym13173016

Abdul Rahim Chethikkattuveli Salih, Arun Asif + Show 8 more

Open Access

https://doi.org/10.3390/polym13173016

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Abstract

The cellular microenvironment is influenced explicitly by the extracellular matrix (ECM), the main tissue support biomaterial, as a decisive factor for tissue growth patterns. The recent emergence of hepatic microphysiological systems (MPS) provide the basic physiological emulation of the human liver for drug screening. However, engineering microfluidic devices with standardized surface coatings of ECM may improve MPS-based organ-specific emulation for improved drug screening. The influence of surface coatings of different ECM types on tissue development needs to be optimized. Additionally, an intensity-based image processing tool and transepithelial electrical resistance (TEER) sensor may assist in the analysis of tissue formation capacity under the influence of different ECM types. The current study highlights the role of ECM coatings for improved tissue formation, implying the additional role of image processing and TEER sensors. We studied hepatic tissue formation under the influence of multiple concentrations of Matrigel, collagen, fibronectin, and poly-L-lysine. Based on experimental data, a mathematical model was developed, and ECM concentrations were validated for better tissue development. TEER sensor and image processing data were used to evaluate the development of a hepatic MPS for human liver physiology modeling. Image analysis data for tissue formation was further strengthened by metabolic quantification of albumin, urea, and cytochrome P450. Standardized ECM type for MPS may improve clinical relevance for modeling hepatic tissue microenvironment, and image processing possibly enhance the tissue analysis of the MPS.

Highlights

Organs on a chip (OoC) technology is based on providing a dynamic microenvironment with physiological shear stress for optimum growth and differentiation of tissues emulating human physiology [1]
extracellular matrix (ECM) components such as collagen and fibronectin have been previously used for the attachment of hepatocytes to a biocompatible surface or membranes [20,21,22]
These data showed that all ECMs increased hepatocyte attachment; there was no apparent tissue specificity observed at this stage

Summary

Introduction

Organs on a chip (OoC) technology is based on providing a dynamic microenvironment with physiological shear stress for optimum growth and differentiation of tissues emulating human physiology [1]. Cells are suspended in hydrogels or attached to a surface with supporting extracellular matrix (ECM). ECM interactions influence cell adhesion, cell differentiation, cell–cell communication, tissue repair, tissue regeneration, and tumor growth processes [3]. Cell isolation from native ECM causes loss of cellular polarity and important molecular characteristics [4]. Available ECM components are typically employed as cell culture substrata. Exclusive ECM components, such as fibronectins, collagens, and laminins have been utilized in cell culture for years and have been proved to profoundly impact the survival and attachment of cells cultured in vitro, and homeostasis of various cellular functions [5]

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