Cited by 399Pancreatic function and diabetesTissue Engineering and Regenerative MedicineHydrogels: synthesis, properties, applications

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Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials

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Pedraza, Eileen, Coronel, Maria M., Fraker, Christopher A., Ricordi, Camillo, Stabler, Cherie L.·2012·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1113560109PMC PMC3306668

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Abstract

A major hindrance in engineering tissues containing highly metabolically active cells is the insufficient oxygenation of these implants, which results in dying or dysfunctional cells in portions of the graft. The development of methods to increase oxygen availability within tissue-engineered implants, particularly during the early engraftment period, would serve to allay hypoxia-induced cell death. Herein, we designed and developed a hydrolytically activated oxygen-generating biomaterial in the form of polydimethylsiloxane (PDMS)-encapsulated solid calcium peroxide, PDMS-CaO 2 . Encapsulation of solid peroxide within hydrophobic PDMS resulted in sustained oxygen generation, whereby a single disk generated oxygen for more than 6 wk at an average rate of 0.026 mM per day. The ability of this oxygen-generating material to support cell survival was evaluated using a β cell line and pancreatic rat islets. The presence of a single PDMS-CaO 2 disk eliminated hypoxia-induced cell dysfunction and death for both cell types, resulting in metabolic function and glucose-dependent insulin secretion comparable to that in normoxic controls. A single PDMS-CaO 2 disk also sustained enhanced β cell proliferation for more than 3 wk under hypoxic culture conditions. Incorporation of these materials within 3D constructs illustrated the benefits of these materials to prevent the development of detrimental oxygen gradients within large implants. Mathematical simulations permitted accurate prediction of oxygen gradients within 3D constructs and highlighted conditions under which supplementation of oxygen tension would serve to benefit cellular viability. Given the generality of this platform, the translation of these materials to other cell-based implants, as well as ischemic tissues in general, is envisioned.

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Authors: Pedraza, E., Coronel, M. M., Fraker, C. A., Ricordi, C., & Stabler, C. L.
Affiliations: University of Miami (US)
Diabetes Research Institute and
ORCID: Pedraza, Eileen
Fraker, Christopher A.
Ricordi, Camillo
Stabler, Cherie L.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2012-02-27
Volume: 109
Issue: 11
Pages: 4245-4250
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1113560109
PMC: PMC3306668
OpenAlex: W2109949410
Cited by: 399
References: 27
Citations by year: 2026: 15 · 2025: 21 · 2024: 27 · 2023: 44 · 2022: 25 · 2021: 48 · 2020: 33 · 2019: 38 · 2018: 30 · 2017: 34 · 2016: 26 · 2015: 12 · 2014: 19 · 2013: 25 · 2012: 2
FWCI: 18.89
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Defense
Diabetes Research Institute Foundation
National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK083096)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
Keywords: hypoxia, calcium peroxide, polydimethylsiloxane encapsulation, pancreatic beta cells, pancreatic islets, tissue engineering, oxygen gradients, cell survival, glucose-dependent insulin secretion, beta-cell proliferation
MeSH terms: Animals, Biocompatible Materials, Cell Survival, Dimethylpolysiloxanes, Hydrolysis, Oxides, Oxygen, Sepharose, Time Factors, Cell Hypoxia, Cell Death, Calcium Compounds, Coculture Techniques, Cell Proliferation, Insulin-Secreting Cells, Mice, Rats

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Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials

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