Extracorporeal shock‐wave therapy enhanced wound healing via increasing topical blood perfusion and tissue regeneration in a rat model of STZ‐induced diabetes

Abstract

Extracorporeal shock-wave therapy (ESWT) has a significant positive effect in accelerating chronic wound healing. However, the bio-mechanisms operating during ESWT of wounds remain unclear. This study investigated the effectiveness of ESWT in the enhancement of diabetic wound healing. A dorsal skin defect (area, 6 x 5 cm) in a streptozotocin-induced diabetes rodent model was used. Fifty male Wistar rats were divided into five groups. Group I consisted of nondiabetic control; group II included diabetic control receiving no ESWT; group III included rats that underwent one session of ESWT (ESW-1) on day 3 (800 impulses at 0.09 mJ/mm(2)) postwounding; group IV included rats that underwent two sessions of ESWT (ESW-2) on days 3 and 7; and group V included rats that underwent three sessions of ESWT (ESW-3) on days 3, 7, and 10. The wound healing was assessed clinically. Blood perfusion scan was performed with laser Doppler. The VEGF, eNOS, and PCNA were analyzed with immunohistochemical stain. The results revealed that the wound size was significantly reduced in the ESWT-treated rats, especially in the ESW-2 and ESW-3 groups, as compared with the control (p<0.01). Blood perfusion was significantly increased after ESWT compared with the controls. Histological findings revealed a significant reduction in the topical pro-inflammatory reaction in the ESWT group as compared with the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and PCNA expressions were observed in the ESWT group, especially in the ESW-2 and ESW-3 groups, as compared with the control. In conclusion, treatment with an optimal session of ESWT significantly enhanced diabetic wound healing associated with increased neo-angiogenesis and tissue regeneration, and topical anti-inflammatory response.

Shock Wave Treatment Enhances Cell Proliferation and Improves Wound Healing by ATP Release-coupled Extracellular Signal-regulated Kinase (ERK) Activation

“…Our in vivo studies further revealed that ESWT improves wound healing in a rat ischemic skin flap model and that Erk1/2 signaling is involved in this process. Taken together with previous reports (5,16) and with our in vitro and in vivo findings, this suggests that ESWT promotes wound healing by local ATP release and P2 receptor activation that foster cell proliferation and tissue remodeling via Erk1/2 activation.…”

“…of ESWT, namely its ability to induce the healing of chronic ulcers and non-healing wounds (1)(2)(3)(4)(5).…”

“…In addition to the accelerated healing rates in patients treated with ESWT, this therapeutic approach is noninvasive and cost-effective. Despite the growing evidence of the beneficial clinical effects of ESWT in treating musculoskeletal disorders and soft tissue wounds in animal models and clinical studies (3)(4)(5)(6)(7)(8)(9)(10), the underlying mechanisms of how ESWT exerts these beneficial effects have remained unclear.…”

“…In recent years, various research groups have focused on the angiogenic impact of shock waves (4,5,12,13). They have shown that ESWT up-regulates angiogenesis via mediators such as vascular endothelial growth factor (VEGF), endothelial nitric-oxide synthase, hypoxia-inducible factor 1a, and CD31 (4,5,14,15). ESWT was shown to augment the expression of proliferating cell nuclear antigen and the recruitment of fibroblasts and to down-regulate production of proinflammatory cytokines (16).…”

Extracorporeal Shock Wave Treatment Improves Incisional Wound Healing in Diabetic Rats

“…In a prospective study, Wang et al (2009) compared the effect of ESWT with that of traditional hyperbaric oxygen therapy on chronic diabetic foot ulcers, and concluded that ESWT achieved better clinical results than hyperbaric oxygen therapy. Although the mechanism underlying low-energy ESWT-mediated improvement of wound healing is not completely known, it is widely thought that its positive effect is mainly related to its role in promoting the revascularization and tissue regeneration in wounds (Kuo et al 2009a).…”