@article {1655711,
	title = {Continuous NPWT Regulates Fibrosis in Murine Diabetic Wound Healing},
	journal = {Pharmaceutics},
	volume = {14},
	number = {10},
	year = {2022},
	month = {2022 Oct 06},
	abstract = {Scarring is associated with significant morbidity. The mechanical signaling factor yes-associated protein (YAP) has been linked to Engrailed-1 (En1)-lineage positive fibroblasts (EPFs), a pro-scarring fibroblast lineage, establishing a connection between mechanotransduction and fibrosis. In this study, we investigate the impact of micromechanical forces exerted through negative pressure wound therapy (NPWT) on the pathophysiology of fibrosis. Full-thickness excisional dorsal skin wounds were created on diabetic (db/db) mice which were treated with occlusive covering (control) or NPWT (continuous, -125 mmHg, 7 days; NPWT). Analysis was performed on tissue harvested 10 days after wounding. NPWT was associated with increased YAP (p = 0.04) but decreased En1 (p = 0.0001) and CD26 (p \&amp;lt; 0.0001). The pro-fibrotic factors Vimentin (p = 0.04), α-SMA (p = 0.04) and HSP47 (p = 0.0008) were decreased with NPWT. Fibronectin was higher (p = 0.01) and collagen deposition lower in the NPWT group (p = 0.02). NPWT increased cellular proliferation (p = 0.002) and decreased apoptosis (p = 0.03). Western blotting demonstrated increased YAP (p = 0.02) and RhoA (p = 0.03) and decreased Caspase-3 (p = 0.03) with NPWT. NPWT uncouples YAP from EPF activation, through downregulation of Caspace-3, a pro-apoptotic factor linked to keloid formation. Mechanotransduction decreases multiple pro-fibrotic factors. Through this multifactorial process, NPWT significantly decreases fibrosis and offers promising potential as a mode to improve scar appearance.},
	issn = {1999-4923},
	doi = {10.3390/pharmaceutics14102125},
	author = {Wu, Mengfan and Matar, Dany Y and Yu, Zhen and Chen, Ziyu and Knoedler, Samuel and Ng, Brian and Darwish, Oliver A and Sohrabi, Sadaf and Friedman, Leigh and Haug, Valentin and Murphy, George F and Rinkevich, Yuval and Orgill, Dennis P and Panayi, Adriana C}
}
