In the intraperitoneal site, the O 2 tension (pO 2) is approximately 40 mmHg, and in the subcutaneous site, likely lower 12.Ī thoroughly investigated approach to improve graft oxygenation is to supply exogeneous O 2 in situ. It is well documented that O 2 is more severely limited than other nutrients because of the relative scarcity of extravascular O 2 in vivo 11. Therefore, encapsulated cells are entirely dependent on O 2 and other nutrients by passive diffusion from the surrounding blood vessels at the exterior of the device 10. Unlike traditional organ transplantations (e.g., pancreas transplantation), wherein the host circulatory system is connected to the transplanted organ via surgical vascular anastomosis 9, most islet encapsulation devices (i.e., bioartificial pancreases) remain isolated from the host’s bloodstream after transplantation. Islet transplantation via the injection of isolated islets into the liver portal vein or onto the omentum has shown the potential to normalize glycemic control without exogenous insulin in clinical trials, but life-long recipient immunosuppression is required with this procedure 6, 7.Ĭell encapsulation technology offers to protect cells from immune rejection by isolating them from the host using an artificial, semipermeable material, thereby overcoming the need for immunosuppressive agents 2, 8. In particular, the delivery of islets (or stem cell-derived β-cells) represents a promising therapy for type 1 diabetes (T1D). Finally, the therapeutic potential of the device is demonstrated through the correction of diabetes in immunocompetent mice using rat islets for over 6 months.Ĭell-based therapies are attractive treatments for a variety of diseases, such as diabetes 1, 2, liver diseases 3, and hemophilia 4, 5.
A computational model, validated by in vitro analysis, predicts that cells and islets maintain high viability even in a thick (6.6 mm) device. We incorporate the scaffold into a bulk hydrogel containing cells, which facilitates rapid O 2 transport through the whole system to cells several millimeters away from the device-host boundary. Inspired by the natural gas-phase tracheal O 2 delivery system of insects, we present herein the design of a biomimetic scaffold featuring internal continuous air channels endowed with 10,000-fold higher O 2 diffusivity than hydrogels.
This constrains the maximum permitted distance between the encapsulated cells and host site to within a few hundred micrometers to ensure cellular function. In such systems, cellular oxygen (O 2) delivery is limited to slow passive diffusion from transplantation sites through the poorly O 2-soluble encapsulating matrix, usually a hydrogel. Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes.