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Cited by 202Tissue Engineering and Regenerative MedicinePancreatic function and diabetesHydrogels: synthesis, properties, applications

Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation

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Liu, Qingsheng, Chiu, Alan, Wang, Long-Hai, An, Duo, Zhong, Monica, Smink, Alexandra M., de Haan, Bart J., de Vos, Paul +10 more·2019·Nature Communications
DOI 10.1038/s41467-019-13238-7PMC PMC6868136
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Abstract

Foreign body reaction (FBR) to implanted biomaterials and medical devices is common and can compromise the function of implants or cause complications. For example, in cell encapsulation, cellular overgrowth (CO) and fibrosis around the cellular constructs can reduce the mass transfer of oxygen, nutrients and metabolic wastes, undermining cell function and leading to transplant failure. Therefore, materials that mitigate FBR or CO will have broad applications in biomedicine. Here we report a group of zwitterionic, sulfobetaine (SB) and carboxybetaine (CB) modifications of alginates that reproducibly mitigate the CO of implanted alginate microcapsules in mice, dogs and pigs. Using the modified alginates (SB-alginates), we also demonstrate improved outcome of islet encapsulation in a chemically-induced diabetic mouse model. These zwitterion-modified alginates may contribute to the development of cell encapsulation therapies for type 1 diabetes and other hormone-deficient diseases.

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  • A zwitterionic modification to alginate microcapsules significantly reduced fibrosis due to its ability to resist protein adsorption and cell attachment.

    “Another group added a zwitterioinic modification to alginate microcapsules to significantly reduce fibrosis due to its ability to resist protein adsorption and cell attachment.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [106]

    The Results (Development of zwitterionically modified alginates; Zwitterionically modified alginates mitigate CO in mice) report reduced protein adsorption and significantly reduced cell adhesion. The Results (FBR mitigation in dogs and pigs) describe thinner fibrous tissue around modified capsules, but say this fibrosis-related finding was qualitative and lacked a statistical comparison. The Discussion treats reduced protein adsorption as a likely contributor to reduced cellular overgrowth, while saying the exact mechanisms need further study; the claim overstates both the significance of the fibrosis finding and the certainty of its cause. (LLM, conf=0.87)

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References 83 · Cited by 202

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Authors
Liu, Q., Chiu, A., Wang, L.-H., An, D., Zhong, M., Smink, A. M., de Haan, B. J., de Vos, P., Keane, K., Vegge, A., Chen, E. Y., Song, W., Liu, W. F., Flanders, J., Rescan, C., Grunnet, L. G., Wang, X., & Ma, M.
Affiliations
  • Cornell University (US)
  • University Medical Center Groningen (NL)
  • Novo Nordisk (Denmark) (DK)
  • University of California, Irvine (US)
Corresponding author
Ma, Minglin
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-11-20
Volume
10
Issue
1
Pages
5262-5262
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-13238-7
PMC
PMC6868136
OpenAlex
W2989764828
Cited by
202
References
83
Citations by year
2026: 18 · 2025: 25 · 2024: 38 · 2023: 27 · 2022: 34 · 2021: 37 · 2020: 22 · 2019: 1
FWCI
22.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
  • JDRF
  • Hartwell Foundation
  • Foundation for the National Institutes of Health (NIH, 1R01DK105967-01A1)
  • Novo Nordisk
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
sulfobetaine, carboxybetaine, cell encapsulation, foreign body reaction, alginate microcapsules, islet encapsulation, type 1 diabetes, fibrosis, implant biocompatibility
MeSH terms
Cell Encapsulation, Alginates, Animals, Betaine, Carbonic Acid, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Dogs, Fibrosis, Foreign-Body Reaction, Swine, Islets of Langerhans Transplantation, Cell Proliferation, Mice, Rats

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