A continuously oxygenated macroencapsulation system enables high-density packing and delivery of insulin-secreting cells
Tung Pham Thanh, Phuong Le Tran, Linda A. Tempelman, Simon G. Stone, Christopher Piccirillo, Alan Li, James A. Flanders, Minglin Ma
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. Insufficient oxygen limits the efficacy of cell encapsulation therapies for type 1 diabetes. Here, the authors develop an implantable system that continuously generates oxygen to support high-density islet cell survival and function, enabling diabetes reversal in rats without immunosuppression.