Negative Pressure Wound Therapy Regulate Lymphatic Vessels Growth in Diabetic Wound Healing in Mice
Chenglong Wang, M.D1, Siqi Fu1, Diane R. Bielenberg, PhD2, Dennis P. Orgill, M.D PhD1, Giorgio Giatsidis, M.D PhD1.
1Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, 2Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Background: Mechanical stimulation is known to accelerate wound healing through the stimulation of mechano-sensitive processes that lead to cell proliferation. Several therapies, collectively known as Negative Pressure Wound Therapies, have been developed to harness these phenomena in a clinical scenario. Here, we investigate using a murine model the effects of NPWT on endothelial vessels to assess whether its differential effects on blood and lymphatic vessels.
Methods: A miniaturized NPWT device was applied to a full-thickness wound in a diabetic mouse model. NPWT used either continuous or cyclical kinetics of stimulation; occlusive dressing served as control (N= 9/group). Endothelial vessels and lymphatic vessels density in wounds was evaluated by immunohistochemistry (respectively CD31 and Podoplanin staining) on samples procured on day 7 and 14 after surgery.
Results: The density of lymphatic vessels in wounds significantly increased in the continuous NPWT group on day 14 (p < 0.05). The commonly used CD31 staining for endothelial (blood and lymphatic) vessels showed a strong expression for blood vessels and a low expression on lymphatic vessels. For the wound bed, the CD31+vessels significantly increased for the cyclical group on day 7 and showed a significant difference for both continuous and cyclical group on day 14 compared to controls (p < 0.05).
Conclusions: This study suggests that continuous NPWT has a lymphangiogenic effect, which may help maintain homeostasis in healing wounds. Future research should ponder the use of CD31 staining to assess angiogenesis as it could possibly over-estimate such effect by incorrectly measuring also some lymphatic vessels.
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