Abstract:
Impaired lymphatic drainage following fracture is a critical factor contributing to delayed bone healing. The underlying mechanisms span multiple stages, including local inflammatory activation, immune imbalance, and failure of tissue repair, involving pathological events such as lympho-platelet thrombus formation, retention of damage-associated molecular patterns (DAMPs), and restricted lymphangiogenesis. These interconnected processes drive macrophage polarization and suppress the function of bone marrow mesenchymal stem cells, thereby disrupting the post-fracture regenerative microenvironment and leading to impaired osteogenesis. This review proposes a tripartite "lymphatic-immune-osteogenic" regulatory axis, focusing on how lymphatic drainage dysfunction affects fracture healing through multiple pathways-such as delayed inflammatory clearance, immune deviation, and impaired stem cell migration. It systematically elucidates the pivotal role of lymphatic dysfunction in the resolution of inflammation and initiation of bone regeneration, and further discusses potential intervention strategies, aiming to provide a theoretical foundation and target insights for developing individualized precision treatment regimens.