Engineering Multilayered Hepatic Cell Sheet Model Using Oxygen-Supplying MeHA/CPO Hydrogel.

Kyungsook Kim, So Hee Han, Jiyoen Oh, Delger Bayarsaikhan, Moon Suk Kim, Dayoen Kim, Teruo Okano, Bonghee Lee

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Article in Bioengineering (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

8 authors.

Kyungsook KimDepartment of Biomedical Engineering, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun 28023, Chuncheongbuk-do, Republic of Korea.

So Hee HanDepartment of Biomedical Engineering, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun 28023, Chuncheongbuk-do, Republic of Korea.

Jiyoen OhDepartment of Biomedical Engineering, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun 28023, Chuncheongbuk-do, Republic of Korea.

Delger BayarsaikhanLee Gil Ya Cancer and Diabetes Institute, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea.

Moon Suk KimDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.

Dayoen KimDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.

Teruo OkanoCell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.

Bonghee LeeLee Gil Ya Cancer and Diabetes Institute, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Three-dimensional (3D) hepatic tissue engineering holds great potential for liver regeneration, disease modeling, and drug screening. These applications require densely layered hepatic tissues that mimic native 3D liver architecture. However, limited oxygen supply and reduced cell viability in densely layered hepatic constructs remain key challenges. To overcome this, this study developed a photo-crosslinkable, oxygen-releasing hydrogel composed of methacrylated hyaluronic acid (MeHA) and calcium peroxide (CPO). The MeHA/CPO hydrogel exhibited favorable rheological properties and sustained oxygen release. Induced pluripotent stem cell-derived hepatocyte (iHep) sheets were cultured with or without MeHA/CPO hydrogel in single- and double-layer formats. The hydrogel enhanced structural integrity and supported the formation of a multilayer (~33 µm). Double-layered iHep sheets with MeHA/CPO showed the significantly increased expression of paracrine factors (HGF, VEGF, Alb) and improved albumin secretion without loss of hepatocyte identity (AFP, HNF4α). This oxygen-releasing system effectively alleviates hypoxic stress, supporting the structural and functional viability of multilayered iHep sheets. Our platform provides a promising approach for engineering metabolically active hepatic tissues and may serve as a foundation for 3D hepatic tissue engineering.

Indexed as

3D hepatic tissueCell sheet technologyiPSC-derived hepatocytesoxygen releasing hydrogel

Identifiers

PMID41155130

DOI10.3390/bioengineering12101132

PMCPMC12561752

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