Repetitive extracorporeal shock wave applications are superior in inducing angiogenesis after full thickness burn compared to single application

Abstract

Objective: Burn wounds remain a challenge due to subsequent wound infection and septicemia, which can be prevented by acceleration of wound healing. The aim of the study was to analyze microcirculation and leukocyte endothelium interaction with particular focus on angiogenesis after full-thickness burn using three different repetitions of low energy shock waves.

Methods: Full-thickness burns were inflicted to the ears of hairless mice (n=44; area: 1.6±0.05 mm2 (mean±SEM)). Mice were randomized into four groups: the control group received a burn injury but no shock waves; group A received ESWA (0.03 mJ/mm2) on day one after burn injury; group B received shock waves on day one and day three after burn injury; group C ESWA on day one, three and seven after burn injury. Intravital fluorescent microscopy was used to assess microcirculatory parameters, angiogenesis and leukocyte interaction. Values were obtained before burn (baseline value) immediately after and on days 1, 3, 7 and 12 after burn.

Results: Shock-wave treated groups showed significantly accelerated angiogenesis compared to the control group. The non-perfused area (NPA) is regarded as a parameter for angiogenesis and showed the following data on day 12 2.7±0.4% (group A, p=0.001), 1.4±0.5% (group B, p<0.001), 1.0±0.3% (group C, p<0.001), 6.1±0.9% (control group). Edema formation is positively correlated with the number of shock wave applications: day 12: group A: 173.2±9.8%, group B: 184.2±6.6%, group C: 201.1±6.9%, p=0.009 vs. control: 162.3±8.7% (all data: mean±SEM).

Conclusion: According to our data shock waves positively impact the wound healing process following burn injury. Angiogenesis showed significantly improved activity after shock wave application. In all three treatment groups angiogenesis was higher compared to the control group. Within the ESWA groups, double applications showed better results than single application and three applications showed better results than single or double applications.

Keywords: Angiogenesis; Intravital fluorescent microscopy; Microcirculation; Wound healing.