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Wound healing is a multistep process involving interaction of various cell types, mediators such as cytokines, inflammation, and generation of new tissue. Both the blood and lymphatic vasculature aid in tissue repair, during which new vessels are generated by angiogenesis and lymphangiogenesis, respectively. We utilized a mouse full-thickness wound model to detect lymphangiogenesis near an incisional wound by near-infrared fluorescence (NIRF) imaging at multiple time points post-incision (PI). In addition, the systemic affects of locally administered vascular endothelial growth factor (VEGF)-C were investigated by measuring peripheral blood cytokine levels in treated and untreated animals. Lymphangiogenesis was detected at the wound site by NIRF imaging by day 7 or 8 PI and confirmed by intravital imaging, while angiogenesis was observed by day 2 or 3 PI. Interleukin (IL)-1α and IL-3 levels were significantly increased at day 7 and 21, respectively, relative to pre-incision levels found in the periphery of VEGF-C-treated mice. Also, regulated-upon-activation, normal T-cell expressed and secreted (RANTES) levels were significantly higher in VEGF-C-treated animals when compared to saline-treated mice at day 21 PI. Our findings demonstrate that NIRF imaging can be utilized to detect early lymphangiogenesis during wound healing, and local VEGF-C administration may help induce this process via increasing systemic levels of wound-healing mediators.
A. Jordan (Wed,) studied this question.