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The Extracellular Matrix01:42

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Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
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Extracellular Matrix Optimization for Enhanced Physiological Relevance in Hepatic Tissue-Chips.

Abdul Rahim Chethikkattuveli Salih1, Kinam Hyun1, Arun Asif1

  • 1Department of Mechatronics Engineering, Jeju National University, Jeju-si 63243, Korea.

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|September 10, 2021
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Summary

Standardized extracellular matrix (ECM) coatings enhance liver tissue development in microphysiological systems (MPS). Image processing and TEER sensors aid in analyzing tissue formation for improved drug screening and liver modeling.

Keywords:
TEERcollagenextracellular matriximage analysismicrophysiological systemtight junction proteins

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Hepatology

Background:

  • The cellular microenvironment, significantly shaped by the extracellular matrix (ECM), dictates tissue development patterns.
  • Hepatic microphysiological systems (MPS) are emerging tools for liver drug screening, but require optimization for physiological relevance.
  • Standardized ECM surface coatings in microfluidic devices can enhance the organ-specific emulation capabilities of MPS.

Purpose of the Study:

  • To investigate the impact of various extracellular matrix (ECM) coatings on hepatic tissue formation within microphysiological systems (MPS).
  • To evaluate the utility of image processing tools and transepithelial electrical resistance (TEER) sensors for analyzing tissue development in MPS.
  • To optimize ECM concentrations and types for improved hepatic tissue modeling and drug screening applications.

Main Methods:

  • Hepatic tissue formation was studied using microfluidic devices coated with varying concentrations of Matrigel, collagen, fibronectin, and poly-L-lysine.
  • Transepithelial electrical resistance (TEER) sensors and an intensity-based image processing tool were employed to monitor tissue development.
  • A mathematical model was developed and validated using experimental data to determine optimal ECM concentrations.
  • Metabolic functions (albumin, urea, cytochrome P450) were quantified to further assess tissue viability and function.

Main Results:

  • Specific extracellular matrix (ECM) coatings and concentrations were identified to significantly improve hepatic tissue formation in MPS.
  • Image processing and TEER sensor data provided reliable metrics for evaluating tissue development capacity under different ECM conditions.
  • Metabolic assays confirmed enhanced liver-specific functions in tissues cultured with optimized ECM coatings.
  • The study demonstrated the synergistic role of ECM coatings, image analysis, and TEER sensing in hepatic MPS development.

Conclusions:

  • Standardized ECM coatings are crucial for enhancing the clinical relevance of MPS in modeling the hepatic microenvironment.
  • Image processing and TEER sensors are valuable tools for the quantitative analysis and optimization of hepatic MPS.
  • Optimized hepatic MPS hold significant potential for more accurate drug screening and human liver physiology modeling.