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Related Concept Videos

Liver Regeneration01:24

Liver Regeneration

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The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
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Perfusable Vascular Network with a Tissue Model in a Microfluidic Device
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Paracrine Factor Local Gradient-Generating System for Engineering Perfusable Vascularized Hepatocyte Tissues with

Yen-Hsiang Huang1, Tadahiro Yamashita1,2, Ryo Sudo1,2

  • 1School of Integrated Design Engineering, Graduate School of Science and Technology, Keio University, Yokohama, Japan.

Advanced Healthcare Materials
|March 16, 2026
PubMed
Summary
This summary is machine-generated.

Engineered liver tissues face vascularization challenges. This study developed a system enabling microvessels to penetrate hepatocyte tissue, promoting regeneration and cell proliferation via perfusion.

Keywords:
fibroblastsgelatin cryogelsmicrofluidic devicesparacrine factorsperfusable vascularized hepatocyte tissuesperfusion‐induced hepatocyte proliferative activityprimary hepatocytes

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Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Hepatology

Background:

  • Donor organ shortages necessitate engineered liver tissues.
  • Vascular integration is a key challenge in liver tissue engineering.
  • Achieving perfusable microvessels within engineered tissues remains difficult.

Purpose of the Study:

  • To develop a system for creating vascularized, perfusable hepatocyte tissues.
  • To recapitulate perfusion-mediated proliferative activity of primary hepatocytes in vitro.
  • To overcome limitations in current liver tissue engineering vascularization strategies.

Main Methods:

  • A paracrine factor local gradient (PFLG)-generating system was developed.
  • Fibroblast-loaded cryogels were integrated with a microfluidic device.
  • Angiogenesis was directed prior to hepatocyte seeding to enable microvessel penetration.

Main Results:

  • Microvessels successfully penetrated the 3D hepatocyte tissue, mimicking in vivo architecture.
  • Engineered tissues showed enhanced hepatocyte polarity and functional bile canaliculi.
  • Perfusion culture significantly induced hepatocyte proliferation (increased Ki67-positive cells) without polarity loss.

Conclusions:

  • Perfusion-mediated cues are critical for inducing hepatocyte cell-cycle re-entry while maintaining polarity.
  • The developed platform supports vascularized, functional liver tissue engineering.
  • This modular system provides a foundation for scalable, transplantable liver tissues.