期刊
SCIENCE ADVANCES
卷 7, 期 20, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd5835
关键词
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资金
- NIH [1R01DK105967-01A1]
- Novo Nordisk Company
- Hartwell Foundation
- Juvenile Diabetes Research Foundation (JDRF) [2-SRA-2018-472-S-B, 3-SRA-2020-883-M-B]
- NSF [DGE-1650441]
- NIH/NCI SBIR grants [R43CA224840, R44CA224840]
- NSF SBIR grant [1819583]
- Directorate For Engineering
- Div Of Industrial Innovation & Partnersh [1819583] Funding Source: National Science Foundation
The study introduces an encapsulation system that produces oxygen for cells from carbon dioxide in a self-regulated manner, improving cell survival in hypoxic conditions. Through simulation-guided optimization, the device successfully maintained normoglycemia in animal experiments, demonstrating its potential to support long-term cellular function.
Cell encapsulation represents a promising therapeutic strategy for many hormone-deficient diseases such as type 1 diabetes (T1D). However, adequate oxygenation of the encapsulated cells remains a challenge, especially in the poorly oxygenated subcutaneous site. Here, we present an encapsulation system that generates oxygen (O-2) for the cells from their own waste product, carbon dioxide (CO2), in a self-regulated (i.e., inverse breathing) way. We leveraged a gas-solid (CO2-lithium peroxide) reaction that was completely separated from the aqueous cellular environment by a gas permeable membrane. O-2 measurements and imaging validated CO2-responsive O-2 release, which improved cell survival in hypoxic conditions. Simulation-guided optimization yielded a device that restored normoglycemia of immunocompetent diabetic mice for over 3 months. Furthermore, functional islets were observed in scaled-up device implants in minipigs retrieved after 2 months. This inverse breathing device provides a potential system to support long-term cell function in the clinically attractive subcutaneous site.
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