Abstract
Chronic wounds in diabetic patients represent an escalating health problem, leading to significant morbidity and mortality. Our group previously reported that whole body low-intensity vibration (LIV) can improve angiogenesis and wound healing in diabetic mice. The purpose of the current study was to determine whether effects of LIV on wound healing are frequency and/or amplitude dependent. Wound healing was assessed in diabetic (db/db) mice exposed to one of four LIV protocols with different combinations of two acceleration magnitudes (0.3 and 0.6 g) and two frequencies (45 and 90 Hz) or in non-vibration sham controls. The low acceleration, low frequency protocol (0.3 g and 45 Hz) was the only one that improved wound healing, increasing angiogenesis and granulation tissue formation, leading to accelerated re-epithelialization and wound closure. Other protocols had little to no impact on healing with some evidence that 0.6 g accelerations negatively affected wound closure. The 0.3 g, 45 Hz protocol also increased levels of insulin-like growth factor-1 and tended to increase levels of vascular endothelial growth factor in wounds, but had no effect on levels of basic fibroblast growth factor or platelet derived growth factor-bb, indicating that this LIV protocol induces specific growth factors during wound healing. Our findings demonstrate parameter-dependent effects of LIV for improving wound healing that can be exploited for future mechanistic and therapeutic studies.
Highlights
Chronic wounds represent an escalating health problem around the world, especially in diabetic patients
Our group demonstrated that whole body low-intensity vibration (LIV) can improve angiogenesis and wound healing in diabetic mice, potentially by increasing growth factors such as insulin-like growth factor (IGF)-1 and vascular endothelial growth factor (VEGF) in the wound (Weinheimer-Haus et al, 2014)
low (0.3 g) acceleration (LL) protocol was the only one to increase external measurements of wound closure on days 6 and 10 post-injury compared to sham control, whereas the LH and high (0.6 g) acceleration (HH) protocols decreased wound closure at all time points (Figure 1)
Summary
Chronic wounds represent an escalating health problem around the world, especially in diabetic patients. Chronic wounds are known to exhibit defects in each phase of healing, including dysregulated inflammation, impaired perfusion and neovascularization, and poor tissue maturation (Blakytny and Jude, 2006), few therapies are available to improve healing of diabetic wounds. Energy-based modalities are often used in conjunction with standard treatments for hard to heal chronic wounds. These treatments use laser, electrical, or mechanical stimulation, in an attempt to modify the cellular and biochemical environment to improve angiogenesis and healing (Ennis et al, 2016; Game et al, 2016; Sousa and Batista Kde, 2016). Much remains to be learned about how LIV signals influence different aspects of wound healing
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