Therapeutic Lymphatic Collecting Vessel Regeneration by Directed Fluid Flow

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DESCRIPTION (provided by applicant): Secondary lymphedema is often acquired as a consequence of axillary dissection, performed in an effort to treat breast cancer. Lymph nodes and associated lymphatic collecting vessels are severed and removed from the axilla during this dissection, reducing lymphatic flow and often causing chronic swelling of the arm. Because swelling of the arm follows injury to the lymphatic system, it has been hypothesized that increased lymphatic growth via growth factor mediated lymphangiogenesis of the lymphatic capillaries may reduce the swelling. However, we have found that functional lymphatic capillary growth may be dependent upon pre-existing interstitial flow. Furthermore, increasing function of lymphatic collecting vessels, as opposed to lymphatic capillaries, may be more important for treating secondary lymphedema. We hypothesize that functional regeneration of the lymphatic collecting vessels is dependent upon pre-existing fluid flow, similar to what we have found with the lymphatic capillaries. We intend to investigate the dependence of functional regeneration of lymphatic collecting vessels on pre-existing fluid flow by employing novel biodegradable conduits to bridge the severed ends of a lymphatic collecting vessel to maintain lymphatic flow and enable functional lymphangiogenesis of collecting vessels through the conduit. Because delivery of excess vascular endothelial growth factor (VEGF)- C to the human may produce harmful side effects, we will investigate Nitric Oxide (NO) release from the bioconduit as an alternative to VEGF-C for therapeutic lymphangiogenesis. Our goal is to determine whether a biodegradable conduit may serve as a bridge for lymphatic fluid transport and promote lymphangiogenesis of lymphatic vessels and whether NO-release from the conduit may increase lymphatic endothelial cell (LEC) migration and proliferation. We plan to evaluate the drug releasing conduits by interpositional grafting into a large lymphatic collecting vessel in the rat. PUBLIC HEALTH RELEVANCE: Secondary lymphedema is often acquired as a consequence of axillary dissection, performed in an effort to treat breast cancer. We hypothesize that functional regeneration of the lymphatic collecting vessels is dependent upon pre-existing fluid flow. We intend to investigate the dependence of functional regeneration of lymphatic collecting vessels on pre-existing fluid flow by employing novel biodegradable conduits to bridge the severed ends of a lymphatic collecting vessel to maintain lymphatic flow and enable functional lymphangiogenesis of collecting vessels through the conduit. We will also investigate Nitric Oxide (NO) release from the bioconduit as an alternative to VEGF-C for therapeutic lymphangiogenesis.