Cell-Seeded Implant for Guided Lymphatic Regeneration

To address the lack of treatment options for lymphedema patients we propose the use of nanopatterned collagen thread-like scaffolds (threads) designed to create new lymphatic channels. We have engineered these nanopatterned threads to closely mimic the native structure of vascular endothelial wall and we find that they provide a favorable environment for lymphatic endothelial cells. The nanopatterned thread aligns the endothelial cells, and regulates their migration along the direction of the nanofibrils. This morphological change is associated with beneficial functional effects, such as reduced expression of endothelial adhesion molecules, and reduced adhesiveness for inflammatory cells. The material enhances human endothelial cell survival after implantation in immunodeficient mice. Finally, the nanopatterned threads enhance perfusion in the murine model of limb ischemia, indicating that the threads may act to enhance the development of collateral channels, perhaps by serving as a favorable environment for endothelial cell proliferation and migration. The nanopatterned thread properties will be tested in rabbit and pig animal models. We plan to upgrade current manufacturing process to GMP grade, and to develop a novel minimally invasive catheter/trocar system for subcutaneous thread delivery, for example, across an area of surgical scar. The optimized nanopatterned thread may also be complexed with VEGF-C.