A continuously oxygenated macroencapsulation system enables high-density packing and delivery of insulin-secreting cells

Tung T. Pham, Phuong L. Tran, Linda A. Tempelman, Simon G. Stone, Christopher Piccirillo, Alan Li, James A. Flanders and Minglin Ma ()
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Tung T. Pham: Cornell University
Phuong L. Tran: Cornell University
Linda A. Tempelman: 89 Rumford Ave
Simon G. Stone: 89 Rumford Ave
Christopher Piccirillo: Cornell University
Alan Li: Cornell University
James A. Flanders: Cornell University
Minglin Ma: Cornell University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-62271-2

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