NanoLymph: Development of a Bioengineered Device for Local Immunomodulation in Cell Transplantation

Cell therapies are emerging as a promising strategy for the treatment of various diseases, aiming to replace or repair damaged tissues. However, immune-mediated rejection remains one of the main obstacles to successful transplantation. Current clinical approaches mostly rely on systemic immunosuppressive treatments, which are associated with severe side effects and can lead to generalized immune dysfunction. To address this limitation, we developed a device capable of releasing chemokines involved in the recruitment and activation of regulatory T cells (Tregs). These cells play a crucial role in establishing a local immunotolerant environment that promotes the engraftment of transplanted cells. The NanoLymph device is fabricated using a biocompatible resin and consists of two chambers: a cell reservoir hosting the therapeutic cells and a drug reservoir releasing a combination of antibodies and cytokines. The device showed good integration with host subcutaneous tissue and increased cellular infiltration, vascularization, and lymphangiogenesis. This work presents the design, characterization, and optimization of the NanoLymph platform, including cell viability assays, in vitro and in vivo Treg recruitment, as well as improvements in the 3D design, assembly process, and its reproducibility. We demonstrated that the device is able to recruit Tregs efficiently and deplete effector T cells, promoting a local immune environment favorable to long-term cell engraftment. These results position NanoLymph as a promising alternative to conventional immunosuppressive therapies, offering a more efficient and sustainable strategy for cell transplantation.