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Related Experiment Video

Updated: Jan 13, 2026

The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture
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Engineering Multilayered Hepatic Cell Sheet Model Using Oxygen-Supplying MeHA/CPO Hydrogel.

Kyungsook Kim1,2, So Hee Han1,3, Jiyoen Oh1,3

  • 1Department of Biomedical Engineering, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun 28023, Chuncheongbuk-do, Republic of Korea.

Bioengineering (Basel, Switzerland)
|October 29, 2025
PubMed
Summary
This summary is machine-generated.

Engineers developed a novel oxygen-releasing hydrogel to improve cell survival in 3D liver tissue engineering. This breakthrough supports the creation of more robust and functional engineered hepatic tissues for regenerative medicine.

Keywords:
3D hepatic tissueCell sheet technologyiPSC-derived hepatocytesoxygen releasing hydrogel

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Hepatology

Background:

  • Three-dimensional (3D) hepatic tissue engineering is crucial for liver regeneration, disease modeling, and drug screening.
  • Dense layering of hepatic tissues is required for native 3D liver architecture mimicry.
  • Hypoxia and reduced cell viability in dense constructs are significant challenges.

Purpose of the Study:

  • To develop a photo-crosslinkable, oxygen-releasing hydrogel to enhance 3D hepatic tissue engineering.
  • To investigate the impact of the hydrogel on cell viability, structural integrity, and function of layered hepatic tissues.
  • To overcome oxygen supply limitations in densely layered hepatic constructs.

Main Methods:

  • Fabrication of a methacrylated hyaluronic acid (MeHA) and calcium peroxide (CPO) hydrogel.
  • Characterization of hydrogel rheological properties and oxygen release kinetics.
  • Culture of induced pluripotent stem cell-derived hepatocyte (iHep) sheets in single- and double-layer formats with and without the MeHA/CPO hydrogel.

Main Results:

  • The MeHA/CPO hydrogel demonstrated sustained oxygen release and favorable rheological properties.
  • The hydrogel enhanced structural integrity and supported the formation of multilayered iHep sheets (~33 µm).
  • Double-layered iHep sheets with MeHA/CPO exhibited increased expression of paracrine factors (HGF, VEGF, Alb), improved albumin secretion, and maintained hepatocyte identity (AFP, HNF4α).

Conclusions:

  • The oxygen-releasing hydrogel effectively alleviates hypoxic stress in multilayered hepatic tissues.
  • This platform supports the structural and functional viability of engineered hepatic tissues.
  • The developed hydrogel system offers a promising foundation for advanced 3D hepatic tissue engineering.