ArticlePloS one2015
Modulation of Huh7.5 spheroid formation and functionality using modified PEG-based hydrogels of different stiffness.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
- Micro Pattern-Based 3D Cell Culture Platform: An Overview of Technologies and Applications.Exploration (Beijing, China) · 2026Review
- Recapitulation of human 3D colorectal cancer model using smart thermo-responsive hydrogel for monitoring angiogenesis.Cancer cell international · 2026Article
- Influence of Structure-Property Relationships of Polymeric Biomaterials for Engineering Multicellular Spheroids.Bioengineering (Basel, Switzerland) · 2025Review
- Scaffold-Free Strategies in Dental Pulp/Dentine Tissue Engineering: Current Status and Implications for Regenerative Biological Processes.Bioengineering (Basel, Switzerland) · 2025Review
- Spheroids from Epithelial and Mesenchymal Cell Phenotypes as Building Blocks in Bioprinting (Review).Sovremennye tekhnologii v meditsine · 2025Review
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- The impact of matrix stiffness on hepatic cell function, liver fibrosis, and hepatocellular carcinoma-Based on quantitative data.Biophysics reviews · 2024Review
- Effect of GelMA Hydrogel Properties on Long-Term Encapsulation and Myogenic Differentiation of CGels (Basel, Switzerland) · 2023Article
- GelMA and Biomimetic Culture Allow the Engineering of Mineralized, Adipose, and Tumor Tissue Human Microenvironments for the Study of Advanced Prostate Cancer In Vitro and In Vivo.Advanced healthcare materials · 2023Article
- Engineering Cell Microenvironment Using Nanopattern-Derived Multicellular Spheroids and Photo-Crosslinked Gelatin/Hyaluronan Hydrogels.Polymers · 2023Article
- A Novel 3D Culture Scaffold to Shorten Development Time for Multicellular Tumor Spheroids.International journal of molecular sciences · 2022Article
- An Engineered Protein-Based Building Block (Albumin Methacryloyl) for Fabrication of a 3D In Vitro Cryogel Model.Gels (Basel, Switzerland) · 2022Article
- Bioinspired Sandcastle Worm-Derived Peptide-Based Hybrid Hydrogel for Promoting the Formation of Liver Spheroids.Gels (Basel, Switzerland) · 2022Article
- 3D Cell Culture Systems: Tumor Application, Advantages, and Disadvantages.International journal of molecular sciences · 2021Review
- Recent Advances in Three-Dimensional Multicellular Spheroid Culture and Future Development.Micromachines · 2021Review
- 3D Tumor Spheroid Models for In Vitro Therapeutic Screening of Nanoparticles.Advances in experimental medicine and biology · 2021Article
- Gaining New Biological and Therapeutic Applications into the Liver with 3D In Vitro Liver Models.Tissue engineering and regenerative medicine · 2020Review
- Review
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- 3D Printed Cartilage-Like Tissue Constructs with Spatially Controlled Mechanical Properties.Advanced functional materials · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Physical cues, such as cell microenvironment stiffness, are known to be important factors in modulating cellular behaviors such as differentiation, viability, and proliferation. Apart from being able to trigger these effects, mechanical stiffness tuning is a very convenient approach that could be implemented readily into smart scaffold designs. In this study, fibrinogen-modified poly(ethylene glycol)-diacrylate (PEG-DA) based hydrogels with tunable mechanical properties were synthesized and applied to control the spheroid formation and liver-like function of encapsulated Huh7.5 cells in an engineered, three-dimensional liver tissue model. By controlling hydrogel stiffness (0.1-6 kPa) as a cue for mechanotransduction representing different stiffness of a normal liver and a diseased cirrhotic liver, spheroids ranging from 50 to 200 μm were formed over a three week time-span. Hydrogels with better compliance (i.e. lower stiffness) promoted formation of larger spheroids. The highest rates of cell proliferation, albumin secretion, and CYP450 expression were all observed for spheroids in less stiff hydrogels like a normal liver in a healthy state. We also identified that the hydrogel modification by incorporation of PEGylated-fibrinogen within the hydrogel matrix enhanced cell survival and functionality possibly owing to more binding of autocrine fibronectin. Taken together, our findings establish guidelines to control the formation of Huh7.5 cell spheroids in modified PEGDA based hydrogels. These spheroids may serve as models for applications such as screening of pharmacological drug candidates.
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