An inverse-breathing encapsulation system for cell delivery

Long Hai Wang, Alexander Ulrich Ernst, James Arthur Flanders, Wanjun Liu, Xi Wang, Ashim K. Datta, Boris Epel, Mrignayani Kotecha, Klearchos K. Papas, Minglin Ma

Research output: Contribution to journalArticlepeer-review

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 (O2) 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. O2 measurements and imaging validated CO2-responsive O2 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.

Original languageEnglish (US)
Article numbereabd5835
JournalScience Advances
Volume7
Issue number20
DOIs
StatePublished - May 2021

ASJC Scopus subject areas

  • General

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