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Recovery from traumatic muscle injuries is typically prolonged and incomplete. Our previous study demonstrated that whole-body low-intensity vibration (LIV) enhances healing in a mouse laceration model. We sought to determine whether locally applied LIV (a) improves muscle repair following injury in mice and (b) is directly transduced by cultured muscle cells, via increased IGF-1 activity. C57BL/6J mice were subjected to laceration of the gastrocnemius muscle and were treated with LIV applied directly to the lower leg for 30 min/day or non-LIV sham treatment (controls) for 7 or 14 days. LIV was also applied to differentiating myotubes in culture for 30 min/day for 3 or 6 days. Compared with control mice, LIV increased myofiber cross-sectional area, diameter, and percent area of peripherally nucleated fibers, and decreased percent damaged area after 14 days of treatment. In cultured myotubes, LIV increased fusion and diameter compared with controls after 6 days of treatment. These LIV-induced effects were associated with increased total Akt on day 7 in injured muscle and on day 3 in myotubes, whereas phosphorylated-to-total Akt ratio increased on day 14 in injured muscle and on day 6 in myotubes but were not associated with increased IGF-1 levels at any time point. These changes were also associated with LIV-induced suppression of FOXO1 and Atrogin-1 gene expression at day 7 in injured muscle. These findings demonstrate that muscle cells can directly transduce LIV signals into increased growth and differentiation, and this effect is associated with increased Akt signaling., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Aim: Investigate the immediate effect of low intensity vibration on skin blood flow and its underlying control mechanisms in healthy human participants., Materials and Methods: One-group pre-post design in a university laboratory setting. Nine adults underwent two bouts of 10-minute vibration (30Hz, peak acceleration 0.4g). Outcome measures include skin blood flow, and skin temperature on the right foot. To examine the control mechanisms underlying the vibration-induced blood flow response, SHORT-TIME Fourier analyses were computed to obtain the spectral densities for three frequency bands: metabolic (0.0095-0.02Hz), neurogenic (0.02-0.06Hz), and myogenic (0.06-0.15Hz). Non-parametric Friedman's tests were computed to compare changes of the outcome measures and control mechanisms over the course of vibration., Results: Vibration increased skin blood flow during both bouts of vibration, however the effect did not last after vibration was terminated. Myogenic spectral density increased during both bouts of vibration, whereas the metabolic and neurogenic spectral densities increased only during the 2nd bout of vibration. Interestingly, only the metabolic spectral density remained elevated after vibration ended., Conclusion: Low intensity vibration produced acute increases in skin blood flow mediated in part by vascular control mechanisms of myogenic origin. Further investigation is warranted to determine whether low intensity vibration induces similar increases in skin blood flow in populations prone to developing chronic non-healing wounds, such as spinal cord injury and diabetes., Competing Interests: The author of this manuscript (Koh) has the following competing interest: patent pending on the application of vibration for therapeutic treatment. The name for the pending patent is, “Method and system for physical stimulation of tissue” (#2013/0165,824). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Cellular energy is required for the healing cascade to occur. A combination of cells, cytokines, chemokines, tissue perfusion, an extracellular matrix, and local forces are also required to allow for human tissue repair to proceed. Although there are many examples of treatment options, energy-based therapies are the least understood, appreciated, and employed by practicing wound care physicians. The recent growth of tissue engineering has encouraged researchers to employ both electrical stimulation and therapeutic ultrasound (US) to stimulate cells, induce migration, and modify tissue constructs., Methods: The authors have reviewed the literature on electrical stimulation, US, and vibrational therapy and are providing an update to a prior 2007 publication on this topic. The hope was to provide a broad exposure to these treatments but not to create a comprehensive review. A table of evidence was generated from the recent literature to help guide treatment decisions for the clinician., Results: In the current literature, there is much debate over which treatment modality, dosage levels, and timing are optimal. There are numerous in-vitro-based publications that describe mechanism of action and several clinical articles that describe effectiveness of electrical stimulation and US, but few well-controlled and/or randomized trials. The absence of level one evidence has hindered the adoption of these techniques throughout the years. Three energy-based treatment options, electrical stimulation, vibration, and US, will be reviewed along with possible clinical applications, Conclusions: : Although most trials are underpowered with inconsistent treatment settings, physical therapy modality use is increasing in the clinical community. Recent guidelines reference the use of these treatments with increasing evidence level recommendations. At the present time, electrical stimulation carries the greatest level of evidence for clinical use.

Macrophages are essential for the efficient healing of various tissues. Although many biochemical signaling pathways have been well characterized in macrophages, their sensitivity to mechanical signals is largely unexplored. Here, we applied low-intensity vibrations (LIV) to macrophages to determine whether macrophages could directly transduce LIV signals into changes in the expression of genes and proteins involved in tissue repair. Two different LIV signal frequencies (30Hz or 100Hz) were combined with two acceleration magnitudes (0.15g or 1g) to generate four distinct LIV signals that were applied to cultured murine macrophages. All four LIV signals significantly increased macrophage number after 3 days of stimulation with the combination of the smallest acceleration and the highest frequency (0.15g at 100Hz) generating the largest response. Compared to non-LIV controls, gene expression of the pro-healing growth factors VEGF and TGF-β increased with all four LIV signals (Day 1). LIV also decreased protein levels of the pro-inflammatory cytokines IL-6, IFN-γ, and TNF-α (Days 1 and 3). These data demonstrate the sensitivity of macrophages to high-frequency oscillations applied at low intensities and may suggest that the benefit of LIV for tissue repair may be based on reducing inflammation and promoting a pro-healing macrophage phenotype., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unlabelled: Variables defining vibration-based biomechanical treatments were tested by their ability to affect the musculoskeleton in the growing mouse. Duration of a vibration bout, but not variations in vibration intensity or number of vibration bouts per day, was identified as modulator of trabecular bone formation rates., Introduction: Low-intensity vibrations (LIV) may enhance musculoskeletal properties, but little is known regarding the role that individual LIV variables play. We determined whether acceleration magnitude and/or the number and duration of daily loading bouts may modulate LIV efficacy., Methods: LIV was applied to 8-week-old mice at either 0.3 g or 0.6 g for three weeks; the number of daily bouts was one, two, or four, and the duration of a single bout was 15, 30, or 60 min. A frequency of 45 Hz was used throughout., Results: LIV induced tibial cortical surface strains in 4-month-old mice of approximately 10 με at 0.3 g and 30 με at 0.6 g. In trabecular bone of the proximal tibial metaphysis, all single daily bout signal combinations with the exception of a single 15 min daily bout at 0.3 g (i.e., single bouts of 30 and 60 min at 0.3 g and 15 and 30 min at 0.6 g) produced greater bone formation rates (BFR/BS) than in controls. Across all signal combinations, 30 and 60 min bouts were significantly more effective than 15 min bouts in raising BFR/BS above control levels. Increasing the number of daily bouts or partitioning a single daily bout into several shorter bouts did not potentiate efficacy and in some instances led to BFR/BS that was not significantly different from those in controls. Bone chemical and muscle properties were similar across all groups., Conclusions: These data may provide a basis towards optimization of LIV efficacy and indicate that in the growing mouse skeleton, increasing bout duration from 15 to 30 or 60 min positively influences BFR/BS.

Chronic wounds represent a significant health problem, especially in diabetic patients. In the current study, we investigated a novel therapeutic approach to wound healing--whole body low-intensity vibration (LIV). LIV is anabolic for bone, by stimulating the release of growth factors, and modulating stem cell proliferation and differentiation. We hypothesized that LIV improves the delayed wound healing in diabetic mice by promoting a pro-healing wound environment. Diabetic db/db mice received excisional cutaneous wounds and were subjected to LIV (0.4 g at 45 Hz) for 30 min/d or a non-vibrated sham treatment (controls). Wound tissue was collected at 7 and 15 d post-wounding and wound healing, angiogenesis, growth factor levels and wound cell phenotypes were assessed. LIV increased angiogenesis and granulation tissue formation at day 7, and accelerated wound closure and re-epithelialization over days 7 and 15. LIV also reduced neutrophil accumulation and increased macrophage accumulation. In addition, LIV increased expression of pro-healing growth factors and chemokines (insulin-like growth factor-1, vascular endothelial growth factor and monocyte chemotactic protein-1) in wounds. Despite no evidence of a change in the phenotype of CD11b+ macrophages in wounds, LIV resulted in trends towards a less inflammatory phenotype in the CD11b- cells. Our findings indicate that LIV may exert beneficial effects on wound healing by enhancing angiogenesis and granulation tissue formation, and these changes are associated with increases in pro-angiogenic growth factors.