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

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.