An inverse-breathing encapsulation system for cell delivery.

Wang, Long-Hai; Ernst, Alexander Ulrich; Flanders, James Arthur; Liu, Wanjun; Wang, Xi; Datta, Ashim K; Epel, Boris; Kotecha, Mrignayani et al. · Sci Adv · 2021

basic_science · Level V

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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.