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Cited by 36Supramolecular Self-Assembly in MaterialsSilk-based biomaterials and applicationsHydrogels: synthesis, properties, applications

Peptide-based scaffolds for the culture and maintenance of primary human hepatocytes

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MacPherson, Douglas, Bram, Yaron, Park, Jiwoon, Schwartz, Robert E.·2021·Scientific Reports
DOI 10.1038/s41598-021-86016-5PMC PMC7990934
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Abstract

We report here the use of a nanofibrous hydrogel as a 3D scaffold for the culture and maintenance of functional primary human hepatocytes. The system is based on the cooperative assembly of a fiber-forming peptide component, fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF), and the integrin-binding functional peptide ligand, Fmoc-arginine-glycine-aspartic acid (Fmoc-RGD) into a nanofibrous gel at physiological pH. This Fmoc-FF/RGD hydrogel was formulated to provide a biomimetic microenvironment with some critical features such as mechanical properties and nanofiber morphology, which were optimized to support hepatocyte culture. The material was shown to support maintenance and function of encapsulated primary human hepatocytes as indicated by actin staining, qRT-PCR, and functional cytochrome P450 assays. The designed gel was shown to outperform Matrigel in cytochrome P450 functional assays. The hydrogel may prove useful for liver development and disease models, as well as providing insights into the design of future implantable scaffolds for the regeneration of liver tissue in patients with liver disease.

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  • Fmoc-FF hydrogels alone failed to maintain hepatocyte viability or function, but addition of integrin-binding RGD dramatically increased cell survival and CYP450 activity, surpassing both 2D cultures and Matrigel for long-term cultures.

    “Self-assembling peptide hydrogels formed from Fmoc-FF alone failed to maintain hepatocyte viability or function, but the addition of integrin-binding motifs such as RGD (Arg-Gly-Asp) dramatically increased cell survival and CYP450 activity, surpassing both 2D cultures and Matrigel for long-term cultures [30].”

    From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [30]

    The Results section (page not provided) reports low viability in Fmoc-FF alone and significantly higher survival and CYP450 activity with Fmoc-FF/RGD. It does not support an unqualified claim that the RGD hydrogel surpassed both comparators in long-term cultures: at day 14, CYP450 function exceeded Matrigel but compared well with the 2D control, while survival was comparable to Matrigel. (LLM, conf=0.89)

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References 48 · Cited by 36

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Authors
MacPherson, D., Bram, Y., Park, J., & Schwartz, R. E.
Affiliations
Weill Cornell Medicine (US)
Corresponding author
Schwartz, Robert E.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-03-24
Volume
11
Issue
1
Pages
6772-6772
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-86016-5
PMC
PMC7990934
OpenAlex
W3138200822
Cited by
36
References
48
Citations by year
2026: 3 · 2025: 8 · 2024: 3 · 2023: 12 · 2022: 8 · 2021: 2
FWCI
0.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • SSRN Electronic Journal (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Biogelx, Ltd
  • National Institutes of Health (1K08DK101754)
  • Center for Advanced Digestive Care Research (1280303000)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
  • Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
peptide hydrogels, nanofibrous scaffolds, primary human hepatocytes, hepatocyte encapsulation, RGD peptide, integrin binding, 3D cell culture, cytochrome P450 activity, biomimetic microenvironment, liver regeneration, liver disease models, implantable scaffolds
MeSH terms
Arginine, Aspartic Acid, Cell Adhesion, Cell Survival, Fluorenes, Glycine, Humans, Peptides, Biomarkers, Gene Expression, Hepatocytes, Tissue Scaffolds, Primary Cell Culture

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