Lymph Drainage during Wound Healing in a Hindlimb Lymphedema Mouse Model

Background: Although lymphedematous skin exhibits delayed wound healing, little is known about lymph drainage during wound healing. We investigated the wound healing process in the presence of lymphatic dysfunction. Methods and Results: The right inguinal lymph nodes (iLNs) and the surrounding tissue were excised in each mouse (the operation side), and a sham operation was performed in the left hindlimb (the control side). The next day, full-thickness wounds were made on both hindlimbs. The right hindlimb exhibited acute edema until day 3; however, it started to improve after day 4, and the wound area and epithelialization ratio were similar on both sides. Indocyanine green (ICG) was injected into both hindlimbs to observe lymph flow. On the operation side, ICG leaked out of the surgical site or remained at the injection site until day 2. Some lymph flow toward the existing lymph vessels was seen on day 3, and on day 10, lymph flow toward the axial LNs was detected on the operation side in all mice. On the operation side, the number of dermal lymph vessels was significantly increased on days 3 and 15. The dermal lymph vessel area of the peripheral wound was significantly smaller on the operation side. Conclusions: In a hindlimb lymphedema mouse model, lymph transiently accumulated in subcutaneous tissue, and then was gradually absorbed by the existing lymph vessels. The increase in the number of lymph vessels contributes to lymph drainage during wound healing. Acute lymphedema because of transient lymphatic dysfunction has little effect on wound healing.