Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials
Open accessAbstract
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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Oxygen generating materials inserted alongside the islet graft improve oxygen levels at the transplantation site, and another strategy directly pumps oxygen into an encapsulation device.
“To specifically improve oxygen levels at the transplantation site, oxygen generating materials have been inserted alongside the islet graft,96,98,99 while another strategy directly pumps oxygen into an encapsulation device92,97.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [96]
The study reports that oxygen-generating PDMS–calcium peroxide disks improved oxygenation and survival in cultured rat islets and 3D constructs (study summary; Coculture methods). It describes use during transplantation as a prospective application, not a demonstrated improvement at a transplantation site (Discussion). The separate claim about pumping oxygen into a device is attached to other citations, not this paper. (LLM, conf=0.86)
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“There are many published mathematical models that describe oxygen transport through engineered tissue, correlating spatial gradients of oxygen concentration to cell density, 19,20 viability, 21–23 metabolism, 24 organization, 25–27 and growth factor expression.”
- Authors
- Pedraza, E., Coronel, M. M., Fraker, C. A., Ricordi, C., & Stabler, C. L.
- Affiliations
- University of Miami (US)
- Diabetes Research Institute and
- 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
- 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 › 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
- 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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