An inverse-breathing encapsulation system for cell delivery.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33990318.
- Also identified by DOI 10.1126/sciadv.abd5835 and PMC identifier 8121434.
- Licence recorded as CC BY-NC.
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Abstract
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<sub>2</sub>) for the cells from their own waste product, carbon dioxide (CO<sub>2</sub>), in a self-regulated (i.e., "inverse breathing") way. We leveraged a gas-solid (CO<sub>2</sub>-lithium peroxide) reaction that was completely separated from the aqueous cellular environment by a gas permeable membrane. O<sub>2</sub> measurements and imaging validated CO<sub>2</sub>-responsive O<sub>2</sub> 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.