Noncontact Phased-Array Ultrasound Facilitates Acute Wound Healing in Mice.

BACKGROUND: We developed a noncontact low-frequency ultrasound device that delivers high-intensity mechanical force based on phased-array (PA) technology (NLFU-PA). It may aid wound healing because it is likely to associate with lower risks of infection and heat-induced pain than conventional ultrasound methods. We hypothesized that the microdeformation it induces accelerates wound epithelialization. This was tested in mice. Its effects on key wound-healing processes, namely, angiogenesis, collagen accumulation, and angiogenesis-related gene transcription, were also examined.

METHODS: Immediately post-wounding, bilateral acute wounds in C57BL/6J mice were NLFU- and sham-stimulated for 1 hour/day for three consecutive days (10 Hz/90.6 Pa). Wound closure (epithelialization) was recorded every 2 days as percent change in wound area relative to baseline. Wound tissue was procured on days 2, 5, 7, and 14 (n=5-6/timepoint) and subjected to histopathology with H-E and Masson's trichrome staining, CD31 immunohistochemistry, and quantitative polymerase-chain reaction analysis.

RESULTS: Compared to sham-treated wounds, NLFU-PA-treated wounds exhibited significantly accelerated epithelialization (65±27% vs. 30±26% closure), angiogenesis (4.6±1.7% vs. 2.2±1.0% CD31+ area), and collagen deposition (44±14% vs. 28±13% collagen density) on days 5, 2, and 5, respectively (all P<0.05). The expression of Notch ligand delta-like 1 protein (Dll1) and Notch1, which participate in angiogenesis, was transiently enhanced by treatment on days 2 and 5, respectively.

CONCLUSIONS: Our NLFU-PA device improved the wound-healing rate. This associated with increased early neovascularization that was followed by high levels of collagen-matrix production and epithelialization. NLFU-PA devices may expand the mechanotherapeutic proangiogenesis field, thereby helping stimulate a revolution in infected wound care.