Development of space keeper strategies for enhanced islet transplantation inside the Neovascularized Implantable Cell Homing Encapsulation (NICHE) device for type 1 diabetes treatment

Type 1 diabetes (T1D) is a chronic autoimmune disease that in 2022 affected approximately 8.75 million individuals worldwide. T1D is characterized by the loss of pancreatic β-cells responsible for producing insulin, a fundamental hormone that regulates blood glucose levels. Patients with T1D require lifelong insulin replacement through multiple daily insulin injections or insulin pump therapy. However, these therapies don’t fully restore glycemic control and don’t prevent T1D long-term complications such as neuropathy, retinopathy, kidney disease, stroke, macrovascular problems and foot damage. Islet transplantation is a promising alternative to restore the insulin production in a more physiological way, but it still faces significant challenges including the lack of donor availability and requirement of lifelong immunosuppression. The Neovascularized Implantable Cell Homing Encapsulation (NICHE) device attempts to overcome these challenges by encapsulating transplanted cells, protecting them with localized immunosuppression while providing a well-vascularized environment to maintain the viability and function of the cells. This study investigates two novel placeholder strategies within the NICHE device to enhance islet distribution and survival. This approach involves promoting the tissue to grow around the placeholder, which is removed after vascularization of the cell reservoir of the NICHE, to obtain an empty space inside the device, into which the islets will be transplanted. The first strategy employs a rigid 3D printed biocompatible placeholder which is inserted before device implantation and surgically removed before islet transplantation. In vivo tests on rats assess blood vessel formation, insert removal, and the transplantation process. The second strategy replaces the rigid placeholder with a thermosensitive polymer made of Poly(N-isopropylacrylamide) (PNIPAm). This approach allows the placeholder to achieve the same effect as the rigid insert with a non-invasive procedure, as it can be flushed out without surgery. In vitro tests are conducted to optimize the polymer solution, materials, and device design, improving the flushing procedure and enhancing islet viability and functionality in vivo.