Lymphangiogenesis in the bone-implant interface of orthopedic implants: importance and consequence

The lymphatic system plays an essential physiological role in homeostasis, interstitial fluid composition, and immunity while impaired lymphatic function has been implicated in a number of pathological conditions, including arthritis and delayed wound healing. This study investigated lymphatic capillary growth and lymphangiogenesis pathways in the bone-implant interface from patients with aseptically loosened prosthetic joints. The newly developed lymphatic specific marker, podoplanin, has enabled the first demonstration of lymphatic capillaries in peri-prosthetic tissues (60% of cases contained podoplanin positive vessels). The pro-lymphangiogenic factor (VEGF-C) and its receptor VEGFR-3 showed high level of expression in these tissues, (often in areas of high levels of wear debris). However despite the upregulation of the lymphangiogenesis pathway by a VEGF-C/VEGFR-3-mediated mechanism, there were relatively few podoplanin positive lymphatic vessels in the bone-implant interface (3.4% of total vessels). This may have important pathological consequences in terms of perpetuating inflammation and edema by inhibiting the removal of macromolecules, cells, and interstitial fluid. The identification of lymphatic vessels with internalized polyethylene wear particles provides evidence of this route of wear debris transportation to distal sites. This paper highlights the importance of lymphatic vessels in the maintenance of local and distal inflammatory responses to prosthetic wear particles.