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Negative Pressure Wound Therapy Stimulates Lymphangiogenesis In Murine Incisional Wound Healing
Adriana C. Panayi, MD, Mengfan Wu, M.D., PhD, Dany Y. Matar, BA, Zhen Yu, M.D., Ph.D., Brian Ng, B.A., Oliver A. Darwish, BA, Valentin Haug, MD, Dennis P. Orgill, M.D., Ph.D..
Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.

PURPOSE: Lymphangiogenesis is central to the process of wound healing as it enables transport of immune cells to and fluid removal away from the wound area. Despite the significant function of the lymphatic system in wound healing, and the frequent clinical use of Negative Pressure Wound Therapy (NPWT) in healing wounds, the impact of mechanical force application on lymphangiogenesis remains to be elucidated. In this study we utilized a murine incisional wound model to investigate the impact of NPWT on lymphatic regeneration.
METHODS: A dorsal incisional skin wound was induced in 30 obese and diabetic mice (db/db) which were then treated either with occlusive covering (Control, n=15) or continuous NPWT (24 hours x 7 days, -125 mmHg; NPWT, n=15). The follow up period was 28 days with tissue harvested on day 10 for histological and molecular analysis. Lymphatic function was assessed on day 28 using Evans Blue staining.
RESULTS: Lymphatic density was significantly increased in the NPWT group, verified by probing with the lymphatic vessel specific markers LYVE-1 (259 vs 148 LYVE-1+/HPF; p=0.01) and Podoplanin (4020 vs 126 PDPN+/HPF; p<0.001). The diameter of the lymphatics was increased with NPWT (289 vs 122 μm; p<0.001). LYVE-1 was upregulated at the protein level as assessed with western blotting (p=0.03). Drainage was enhanced by NPWT, with the Evans Blue positive area being larger in the NPWT group at all timepoints (0, 5, 10, 15, 20, 25 and 30 minutes).
CONCLUSION:
Application of micromechanical forces promotes lymphangiogenesis in incisional wounds. The mechanism is likely multifactorial, with a direct impact on the lymphatic vessels through upregulation of LYVE-1 at the molecular level, and edema-dependent effects on the interstitial hydrostatic and oncotic pressure. Overall, NPWT can be used to stimulate lymphatic growth and function in wound healing or as a therapy for conditions such as lymphedema.


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