A continuously oxygenated macroencapsulation system enables high-density packing and delivery of insulin-secreting cells
The encapsulation of insulin-secreting cells offers a promising strategy for curative treatment of type 1 diabetes without immunosuppression. However, insufficient oxygen within encapsulation systems remains a major challenge, restricting cell survival, function, and scalability. Here, we report an encapsulation platform combining a miniaturized implantable electrochemical oxygen generator (iEOG) with a scalable, linear cell pouch designed for minimally invasive implantation and retrieval. This system enables continuous oxygen supply via electrolysis of tissue moisture, supporting high-density cell encapsulation (60,000 IEQ/mL). Oxygen generated by our system was stable, controllable, and sufficient to maintain cell viability and function under hypoxic (1% O₂) conditions in vitro. In an allogeneic rat model, the oxygenated system implanted subcutaneously reversed diabetes for up to three months without immunosuppression, while non-oxygenated controls remained hyperglycemic. These findings demonstrate the feasibility of sustained oxygenation to enable functional, high-density islet encapsulation in subcutaneous sites, advancing the development of clinically translatable cell-based therapies.
Authors
- James A. Flanders (ORCID: https://orcid.org/0000-0002-9878-5736)
- Alan Li (ORCID: https://orcid.org/0000-0002-2037-6262)
- Minglin Ma (ORCID: https://orcid.org/0000-0002-9553-7526)
- Ciriaco A. Piccirillo (ORCID: https://orcid.org/0000-0002-7703-6779)
- Phuong Le Tran (ORCID: https://orcid.org/0000-0002-8082-0142)
- Tung Pham Thanh (ORCID: https://orcid.org/0000-0002-7242-8976)
- Simon G. Stone (ORCID: https://orcid.org/0000-0001-8461-0559)
- Linda A. Tempelman
Institutions
- Cornell University (US)
- Giner (United States) (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-11
- DOI
- https://doi.org/10.1038/s41467-025-62271-2
- Citations
- 5
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 10.03
Funders
- Hartwell Foundation
- University of Pennsylvania
- Novo Nordisk
- National Institutes of Health