Role of Skin Stretch on Local Vascular Permeability in Murine and Cell Culture Models

This study directly tested whether excessive cyclic skin stretch increases vascular permeability, providing a mechanistic link between tissue tension and prolonged inflammation implicated in hypertrophic scarring and keloids. In vivo, a murine abdominal island skin flap model was mounted on an equibiaxial stretching rig and exposed to 45 minutes of cyclic stretch, followed by intravital tracking of FITC-dextran extravasation. Cyclic stretching (20%,1 Hz) produced marked microvascular leakage across the flap, with permeability increases comparable to histamine challenge and significantly higher fluorescence intensity in a central region of interest versus non-stretched controls. In vitro, endothelial cells were induced to form pseudocapillary networks in an elastic chamber and were subjected to cyclic stretch or histamine; both stimuli induced cell contraction, disrupted intercellular junction integrity, and created gaps within the networks. Fluorescent indicator assays showed stretch-associated signaling characterized by sustained K+ efflux and a milder Ca2+ influx response relative to histamine, implicating early ion-channel-dependent events in stretch-induced barrier breakdown. The findings support a model in which repetitive mechanical tension drives endothelial dysfunction and plasma extravasation, potentially prolonging wound/scar inflammation and promoting pathological scar growth.