Reproducibility of high-resolution laser speckle contrast imaging to assess cutaneous microcirculation for wound healing monitoring in mice.

OBJECTIVE: Laser speckle contrast imaging (LSCI) combines an excellent spatial and temporal resolution, with excellent reproducibility in humans. Recently, high-resolution LSCI (LSCI-HR), coupled or not with oximetry, have been marketed. They are promising approaches to assess wound healing, especially in rodents. However, their reproducibility and performance against a reference technique remain unknown. METHODS: Healthy skin perfusion was evaluated at day 0 and repeated at day 2, using LSCI-HR, high-resolution LSCI with oximetry by reflectance spectrometry (LSCI-OX), compared with laser Doppler imaging (LDI) as a reference. In a second experiment, cutaneous perfusion was measured daily during 8 days after wounding at two different sites. The reproducibility of haemoglobin oxygenation with LSCI-OX was also assessed in the two experiments. Reproducibility was expressed as within-subject coefficients of variation (CV, in %). RESULTS: The inter-day reproducibility of healthy skin perfusion was better when assessed with LSCI-HR and LSCI-OX, compared to LDI (CVs between 12 and 17% and between 26 and 29%, respectively). Inter-site reproducibility of perfusion during wound healing was also better with LSCI-HR compared to LDI (CV = 12% and 23%, respectively). Finally, we observed a good, positive correlation between perfusion measured with LDI and LSCI-HR on the periulcer area (average r = 0.77 ± 0.24). CONCLUSION: Recently developed high-resolution LSCI devices provide good reproducibility to assess healthy and wounded skin perfusion in mice. However, the reproducibility of haemoglobin oxygenation is poor.

Iontophoresis of treprostinil promotes wound healing in a murine model of scleroderma-related ulcers.

OBJECTIVE: Systemic sclerosis (SSc) is a rare, chronic disease characterized by fibrosis, vascular alterations and digital ulcerations. Few drugs have shown efficacy to enhance wound healing of existing SSc-related ulcers. Local delivery of treprostinil, a prostacyclin analogue, may improve wound healing. The present work aimed first at developing a mouse model of SSc-related ulcerations and second at assessing the effect of iontophoresis of treprostinil on wound healing. METHODS: We used two murine models of SSc: chemically induced with HOCl, and urokinase-type plasminogen activator receptor (uPAR)-deficient. Excisional wounding was performed on the dorsal midline with a biopsy punch. Animals were randomized into three groups: treated with electrostimulation alone, with treprostinil iontophoresis or untreated. We assessed wound healing over time, as well as skin microvascular reactivity, inflammation, microvessel density and collagen distribution, before wounding and after re-epithelialization. RESULTS: uPAR-/- mice, but not HOCl-treated mice, showed impaired wound healing and decreased microvascular reactivity compared with their controls. Treprostinil iontophoresis improved wound healing and microvascular density and decreased inflammation in uPAR-/- mice, while electro-stimulation did not. However, treprostinil had no effect on microvascular reactivity and collagen distribution. CONCLUSION: This study suggests that excisional wounds in uPAR-/- mice are a relevant model of SSc-related ulcers. In addition, treprostinil iontophoresis enhances wound healing in this model. Further work in now needed to show whether this effect translates in humans.