BACKGROUND:: External volume expansion (EVE) by suction has been proposed to improve the survival of fat grafting by preparing the recipient site. In previous experimental work, EVE demonstrated the capacity to stimulate cell proliferation, vessel remodeling and adipogenesis. This study investigated possible mechanisms underlying these observed changes.

METHODS:: A miniaturized EVE device was applied to the dorsum of mice for 2 hours. Hypoxia during stimulation was assessed with pimonidazole hydrochloride, and tissue perfusion was measured for up to 2 days via hyperspectral imaging. Treated tissues were evaluated by microscopy for the presence of edema, inflammation, the effects on cell proliferation and vessel remodeling.

RESULTS:: EVE-treated tissues were grossly expanded with 2 hours of stimulation, developing a macroscopic swelling that slowly regressed over the course of hours following stimulus cessation. This gross swelling was reflective of histological signs of intense edema, persistent for at least 1 hour post-EVE. Tissues were hypoxic during stimulation, and hyperspectral imaging demonstrated decreased tissue content of both oxygenated- and deoxygenated-hemoglobin in the first hour after EVE release. The onset of inflammation was already apparent by the end of stimulation, and remained elevated through two days post-EVE. At this time point epidermal and dermal cell proliferation, as well as vascular density, were significantly increased.

CONCLUSIONS:: EVE sets in motion various mechanisms including mechanical stimulation, edema, ischemia and inflammation that over distinct time periods maintain an environment conducive to cell proliferation and angiogenesis, which can be elicited even by a single 2 hour EVE cycle.