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Cited by 84Pancreatic function and diabetesTissue Engineering and Regenerative MedicineHydrogels: synthesis, properties, applications

A bioinspired scaffold for rapid oxygenation of cell encapsulation systems

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Wang, Long-Hai, Ernst, Alexander Ulrich, An, Duo, Datta, Ashim Kumar, Epel, Boris, Kotecha, Mrignayani, Ma, Minglin·2021·Nature Communications
DOI 10.1038/s41467-021-26126-wPMC PMC8494927
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Abstract

Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes. In such systems, cellular oxygen (O 2 ) delivery is limited to slow passive diffusion from transplantation sites through the poorly O 2 -soluble encapsulating matrix, usually a hydrogel. This constrains the maximum permitted distance between the encapsulated cells and host site to within a few hundred micrometers to ensure cellular function. Inspired by the natural gas-phase tracheal O 2 delivery system of insects, we present herein the design of a biomimetic scaffold featuring internal continuous air channels endowed with 10,000-fold higher O 2 diffusivity than hydrogels. We incorporate the scaffold into a bulk hydrogel containing cells, which facilitates rapid O 2 transport through the whole system to cells several millimeters away from the device-host boundary. A computational model, validated by in vitro analysis, predicts that cells and islets maintain high viability even in a thick (6.6 mm) device. Finally, the therapeutic potential of the device is demonstrated through the correction of diabetes in immunocompetent mice using rat islets for over 6 months.

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  • A network of interconnected hydrophobic channels inside an islet-filled alginate hydrogel greatly increased the diffusion of oxygen throughout the device from the surrounding tissue.

    “For instance, a network of interconnected hydrophobic channels inside an islet-filled alginate hydrogel greatly increased the diffusion of oxygen throughout the device from the surrounding tissue.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [100]

  • The interconnected hydrophobic channel design greatly enhanced islet survival upon transplantation into diabetic mice and allowed the device to be scaled up to 6.6 mm thick.

    “This design greatly enhanced islet survival upon transplantation into diabetic mice and allowed the device to be scaled up to 6.6 mm thick.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [100]

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References 73 · Cited by 84

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Authors
Wang, L.-H., Ernst, A. U., An, D., Datta, A. K., Epel, B., Kotecha, M., & Ma, M.
Affiliations
  • Cornell University (US)
  • University of Chicago (US)
Corresponding author
Ma, Minglin
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-10-06
Volume
12
Issue
1
Pages
5846-5846
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-26126-w
PMC
PMC8494927
OpenAlex
W3203180208
Cited by
84
References
73
Citations by year
2026: 9 · 2025: 17 · 2024: 22 · 2023: 25 · 2022: 10 · 2021: 1
FWCI
13.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Foundation for the National Institutes of Health (1R01DK105967-01A1)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
cell encapsulation, oxygenation, biomimetic scaffolds, air channels, hydrogels, islet transplantation, type 1 diabetes, oxygen diffusion, cell viability, computational modeling, rat islets, immunocompetent mice
MeSH terms
Cell Encapsulation, Animals, Cell Survival, Cells, Cultured, Electron Spin Resonance Spectroscopy, Humans, Male, Mice, Inbred C57BL, Oxygen, Rats, Sprague-Dawley, Hydrogels, Biomimetics, Mice, Rats

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