No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Shockwave as Biological Therapeutic Tool: from mechanical stimulation to recovery and healing, through Mechanotransduction
Abstract
⁃Extracorporeal Shock Wave Therapy (ESWT) is a form of "mechanotherapy", that, from its original applications as urological lithotripsy, gained the field of musculo-skeletal diseases as Orthotripsy (mainly tendinopaties and bone regenerative disorders) and Regenerative Medicine as well. ⁃The mechanisms of action of Shock Waves (SW), when applied in non-urological indications, are not related to the direct mechanical effect, but to the different pathways of biological reactions, that derive from that acoustic stimulations, through "mechano-transduction". So, the "mechanical model" of urological lithotripsy has been substituted by a "biological model", also supported by current knowledge in "mechanobiology", the emerging multidisciplinary field of science that investigates how physical forces and changes in cell/tissue mechanics can influence the tissue development, physiology and diseases. ⁃Although some details are still under study, it is known that SW are able to relief pain, as well to positively regulate inflammation (probably as immunomodulator), to induce neoangiogenesis and stem cells activities, thus improving tissue regeneration and healing. ⁃ESWT can be nowadays considered an effective, safe, versatile, repeatable, noninvasive therapy for the treatment of many musculo-skeletal diseases, and for some pathological conditions where regenerative effects are desirable, especially when some other noninvasive/conservative therapies have failed. ⁃Moreover, based on the current knowledge in SW mechanobiology, it seems possible to foresee new interesting and promising applications in the fields of Regenerative Medicine, tissue engineering and cell therapies.
... In any case, animal experiences with shock waves should not be extrapolated directly to human beings since, as Chen et al. have stated, the tolerance to ESWT was different for different species [13]. The clearest response to the authors' erroneous interpretation of the mechanism of action of ESWT can be found in a publication by d' Agostino et al. [14]. When describing the mechanism of action, d' Agostino's publication states that when applied in non-urological indications, the mechanisms of action are not related to a direct mechanical effect such as in lithotripsy, but to pathways of biological reactions, that are triggered by acoustic stimulations, through "mechanotransduction" [14]. ...
... The clearest response to the authors' erroneous interpretation of the mechanism of action of ESWT can be found in a publication by d' Agostino et al. [14]. When describing the mechanism of action, d' Agostino's publication states that when applied in non-urological indications, the mechanisms of action are not related to a direct mechanical effect such as in lithotripsy, but to pathways of biological reactions, that are triggered by acoustic stimulations, through "mechanotransduction" [14]. Hence, the "mechanical model" of urological lithotripsy has been substituted by a "biological model" [14] when treating tendons. ...
... When describing the mechanism of action, d' Agostino's publication states that when applied in non-urological indications, the mechanisms of action are not related to a direct mechanical effect such as in lithotripsy, but to pathways of biological reactions, that are triggered by acoustic stimulations, through "mechanotransduction" [14]. Hence, the "mechanical model" of urological lithotripsy has been substituted by a "biological model" [14] when treating tendons. The peculiar interpretation of the information published by other authors goes beyond shock wave studies in the paper by Han et al. ...
Focused shock waves are a frequently used non-invasive therapeutic option for the treatment of rotator cuff calcifications. Over the last 30 years, numerous studies have been published that support its high level of recommendation. Reports of complications are isolated and very infrequent.
In this communication, we analyze why there are no valid arguments to relate the application of shock waves with rotator cuff injuries.
... Although the breakdown of urinary and gallstones is purely mechanical, low-energy shock waves have shown a mechanotransduction effect on the biochemistry of the cell. This aspect permits us to understand the healing powers of acoustic shock waves in various tissues [27,28]. In fact, when applied in non-urological indications, the mechanisms of action of shock waves are not linked to the direct mechanical effect but to the different types of biological reactions induced by acoustic stimulations through mechanotransduction. ...
... According to the literature, acoustic shock waves enhance not simply healing processes but proper regenerative events, for instance, reducing fibrous tissue at its origin or even remodelling it in a second phase, as in scars [27][28][29]. ...
... It should be emphasized that the pathogenetic mechanism of the formation of capsular fibrosis in silicone prostheses presents several similarities with the fibrotic reaction around the PMMA filler [28]. In fact, it is thought that direct immunostimulation and sub-clinical infection are the main ones responsible for the induction and maintenance of inflammatory reactions, which lead to the overabundant formation of extracellular matrix. ...
Background:
Polymethylmethacrylate (PMMA) fillers are permanent fillers known for their possible side effects. In case of complications, the only possible treatment is surgical removal, followed by procedures to minimize resulting deformity. The aims of this study were (1) to analyse the morphology of the PMMA material in the nodules, (2) to demonstrate that treatment by acoustic wave therapy (AWT) can help the removal of the nodules, and (3) to present an easy procedure to solve deformities.
Methods:
The data of 9 patients who underwent AWT, surgical PMMA removal, and deformity correction by enriched nanograft and dermagraft injections between April 2021 and May 2024 were presented. The leftover aspirated material was analysed by histology and scanning electron microscopy.
Results:
AWT resulted in no complications in all patients. After removal and correction surgeries, minor complications were observed in 5 cases. All the patients were delighted with the aesthetic outcome. In all patients, an important improvement of the deformities, with correction of the volume of the face, was observed. A substantial resolution of the initial clinical symptoms was documented. The ultrastructural analysis highlighted that PMMA appears in the form of laminar or prismatic formations with a paracrystalline structure.
Conclusions:
AWT acted directly on PMMA to facilitate its removal and reduce fibrosis around the PMMA filler. The lack of volume correlated with PMMA removal was resolved with the enriched nanograft and dermagraft injections, which led to very satisfying aesthetic results.
Level of evidence v:
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
... 18 El efecto puramente mecánico solo es efectivo en el caso de la destrucción de cálculos, que son acúmulos minerales inertes. En los tejidos vivos, el mecanismo de acción es biológico, se basa en el fenómeno de "mecanotransducción". 12,13,19 Las células y la matriz extracelular son influidas por los estímulos mecánicos. Estas estructuras reconocen los estímulos mecánicos y generan una respuesta biológica. ...
... Estas estructuras reconocen los estímulos mecánicos y generan una respuesta biológica. 12,13,19 Es una paradoja que, en una especialidad que aplica la mecanotransducción desde hace más de un siglo, no se interprete fácilmente este mecanismo de acción. Todos los traumatólogos sabemos que, al dar carga a una fractura en el momento oportuno y en condiciones adecuadas, el proceso de consolidación se acelera. ...
... El proceso tiene cuatro etapas: física, físico-química, química y biológica. 12,19 El núcleo celular estimulado determina la liberación de exosomas con efectos angiogénicos. [19][20][21][22] La vasculogénesis y la angiogénesis son mecanismos de acción fundamentales bien estudiados en las ondas de choque focales. ...
... Several studies have demonstrated the safety and effectiveness of ESWT in pain relief, clinical improvements and calcification resorption in patients with RCCT (Auersperg & Trieb, 2020;De la Corte-Rodríguez et al., 2023;Ioppolo et al., 2014). The mechanism of action and effects of F-and R-SWT may differ because the bioeffects are related to the pressure waveform (Moya et al., 2018;d'Agostino et al., 2015). F-SWT and R-SWT can complement each other (Moya et al., 2018;d'Agostino et al., 2015). ...
... The mechanism of action and effects of F-and R-SWT may differ because the bioeffects are related to the pressure waveform (Moya et al., 2018;d'Agostino et al., 2015). F-SWT and R-SWT can complement each other (Moya et al., 2018;d'Agostino et al., 2015). While F-SWT is suitable for treating small and deep areas, R-SWT is suitable for treating large and surface areas (Moya et al., 2018;d'Agostino et al., 2015). ...
... F-SWT and R-SWT can complement each other (Moya et al., 2018;d'Agostino et al., 2015). While F-SWT is suitable for treating small and deep areas, R-SWT is suitable for treating large and surface areas (Moya et al., 2018;d'Agostino et al., 2015). The mechanism of action of ESWT on calcific tendinopathy is still debated but is believed to be effective through both physical and biological effects (Chianca et al., 2018;Robinson et al., 2021). ...
Purpose
To investigate if Extracorporeal Shock Wave therapy (ESWT) is effective in reducing pain and disability, in improving function, quality of life and complete resorption rate of calcification in patients with Rotator Cuff Calcific Tendinopathy. To investigate which modality of ESWT brings the greatest clinical improvements between High (HE)‐SWT and Low Energy (LE)‐SWT and between Focal (F)‐SWT and Radial (R)‐SWT.
Methods
MEDLINE, EMBASE, CENTRAL Database, and PEDro databases until February 2024 were searched. Study registers were further investigated. The Risk of Bias (RoB) was assessed with the Revised Cochrane RoB Tool (RoB 2). The certainty of evidence was rated with GRADE.
Results
Twenty‐one randomized controlled trials were included. None was judged as overall low RoB. Comparing ESWT and Ultrasound Guided Needling Procedures (USGNP), the pooled results reported a significant difference favoring USGNP in pain at <24 and <48 weeks (MD = 1.17, p = 0.004, I ² = 59%; MD = 1.31, p = 0.004, I ² = 42%, respectively). Comparing ESWT and sham‐ESWT, the pooled results reported a clinically significant difference favoring ESWT in pain and function at 24 weeks (MD = −5.72, p < 0.00001, I ² = 0%; Standardized Mean Difference = 2.94, p = 0.02 I ² = 98%, respectively). Comparing HE‐SWT and LE‐SWT, HE‐SWT was statistically and clinically superior in pain and function at <24 weeks (MD = −1.83, p = 0.03, I ² = 87%; MD = 14.60, p = 0.002, I ² = 77%, respectively) and showed a significantly higher complete resorption rate of calcification at 12 weeks (Risk Ratio = 2.53, p = 0.001, I ² = 0%). F‐SWT and R‐SWT appear equally effective in reducing pain, improving disability and resorption rate. The certainty of evidence was rated as very low through GRADE approach.
Conclusion
USGNP was statistically superior to ESWT in pain reduction at <24 and <48 weeks. ESWT was clinically better to sham‐ESWT in pain reduction and function improvement at 24 weeks. HE‐SWT was clinically more effective than LE‐SWT in reducing pain, improving function at <24 weeks, and resolving calcific deposits at 12 weeks, while no differences between F‐SWT and R‐SWT were reported.
... ESWT can also promote neovascularization by increasing the expression of growth factors related to angiogenesis such as vascular endothelial growth factor and nitric oxide, thus improving blood flow and local tissue perfusion [24][25][26]. Furthermore, ESWT can modulate the immune response and cellular inflammation by regulating macrophage activity, leukocyte infiltration, cytokine, and chemokine production [26][27][28]. Again, there are several clinical observational studies on the beneficial effects of ESWT on pain relief in different acute and chronic musculoskeletal pain conditions [18,22,25]. ...
... Thus, ESWT has become a popular noninvasive and safe therapeutic intervention to reduce pain and promote functional recovery in several musculoskeletal disorders, such as lateral epicondylitis, calcific and non-calcific shoulder tendinitis, Achilles tendinopathy, and plantar fasciitis [22,[29][30][31][32][33][34][35][36]. In general, two different types of ESWT are used in clinical practice, namely, radial and focal shockwave therapy, which differ in terms of the device used, the characteristics of the generated waveform, the depth of impact, and energy intensities [28]. While most research reports the use of focal or radial ESWT in isolation as single treatment modalities, a few recent studies demonstrate promising results in terms of improvement in pain and function when both devices are used in combination within the very same treatment session (i.e., combined shockwave therapy) [37][38][39][40][41]. ...
Background: Gluteus medius tendinopathy is amongst the most prevalent lower limb tendinopathies and is now recognized as the primary cause of insidious lateral hip pain. Typically affecting middle-aged women, this condition causes disability and reduced quality of life as it negatively impacts most daily life activities. Several studies demonstrate that extracorporeal shockwave therapy is effective in reducing pain and promoting functional recovery in several musculoskeletal disorders including tendinopathies. However, most published data are limited to evaluating focal or radial shockwaves as single interventions. Contrariwise, there is little evidence reporting the use of combined ESWT treatment and outcomes for managing tendon pathologies, and no data are reported on combined ESWT for gluteus medius tendinopathy. Objectives: The aim of this study was to evaluate the clinical outcomes of combined ESWT in gluteus medius tendinopathy. Methods: Medical charts of 11 consecutive patients with gluteal tendinopathy confirmed by ultrasound who underwent a combined ESWT protocol were reviewed. Changes in pain severity and lower limb function were evaluated using the numerical rating scale, the Victorian Institute of Sports Assessment for Gluteal tendinopathy questionnaire, and the Roles and Maudsley score. Clinical outcome measurements were collected at baseline (T0), 2 months after combined ESWT (T1), and at long-term follow-up (T2), at least 10 months post-treatment (mean 26 months). Results: The mean age of the sample was 62.55 ± 3.17 years. A marked prevalence of females was recorded (nine subjects, 81.8%). A significant improvement was observed in all outcome criteria both at short- and long-term follow-up after combined ESWT compared to baseline (p < 0.05). Treatment success rates were 90.9% and 81.8% at T1 and T2, respectively. Conclusions: Combined ESWT is effective and safe for patients with gluteal tendinopathy, with good long-term results in terms of pain relief and improved functional impairment.
... The pressure waves generated by radial extracorporeal shockwave travel through body fluids and soft tissues to reach the target area, where they produce both mechanical and cellular effects. e Effect of Radial Extracorporeal Shockwave Therapy on Pain Intensity Level in Patient with Calcaneal Spur SEEJPH Volume XXV S1, 2024, ISSN: 2197-5248;Posted: 05-11-2024 These effects include transient disturbance of the neuronal cell membrane, increase in the tissue permeability, encourage tissue regeneration and neovascularization, all of which contribute to the analgesic effect of radial extracorporeal shockwave [15]. Radial extracorporeal shockwave presents a viable alternative to surgical intervention and steroid injections for treating heel pain but research on its effect on calcaneal spur pain remains limited [16]. ...
... These inducing of release of fascial tissue by the mechanical stimulation [16], analgesia by overstimulation [3], modulation of macrophage activity, reduction of cellular inflammation, reduction of the leukocyte infiltration, and down-regulation of the cytokine production [18]. Additionally, radial extracorporeal shockwave promotes angiogenesis by enhancing the release of nitric oxide which in turn accelerate the healing process [15,16,19,20]. ...
Background: Heel pain is a common musculoskeletal issue that significantly impacts patient daily activities and, consequently, their quality of life. This clinical study aims to evaluate the effectiveness of radial extracorporeal shockwave therapy in reducing pain intensity in patients with calcaneal spurs.Objective: To investigate the effects of radial extracorporeal shockwave therapy on pain intensity in patient with calcaneal spur.Methods: A total of 60 patients diagnosed with calcaneal spurs based on clinical examination and lateral radiography between September 2022 and June 2023 were included in this study. Participants were randomly assigned to two groups: Group A (radial extracorporeal shockwave therapy) and Group B (traditional physical therapy). All participants followed an exercise program; however, those in Group A received six sessions of radial extracorporeal shockwave therapy (10 Hz, 2000 pulses, at 2.4 bar). The Visual Analog Scale (VAS) was used to assess pain intensity both before and after treatment in all participants.Results: No significant differences were observed between Group A and Group B regarding gender, affected side, condition distribution, age, weight, height, or BMI (p > 0.05). Both groups experienced significant reductions in VAS scores post-treatment (p < 0.001); however, Group A demonstrated a greater improvement, with a percentage reduction in pain of -50.65%, compared to -28.17% in Group B. Additionally, post-treatment VAS scores were significantly lower in Group A than in Group B (p = 0.003), indicating that shockwave therapy yielded a more substantial reduction in painConclusions: Both radial extracorporeal shockwave therapy and traditional physical therapy programs significantly reduced pain intensity in patients with calcaneal spurs, with a favorable effect observed for radial extracorporeal shockwave therapy. These methods can be considered effective, safe, and conservative treatment options for managing calcaneal spurs.
... Initial medical use of shockwaves was in lithotripsy procedures, where incidental effects were observed in iliac crest bone hypertrophy [1,11]. Although the mechanism is not entirely understood, ESWT may have therapeutic effects through cellular mechanotransduction that alters pain signaling and promotes tissue regeneration through increased collagen synthesis, osteoprogenitor differentiation, and leukocyte proliferation [4,12,[44][45][46]. Two primary forms of ESWT are used in clinical practice. ...
Background: Tendinopathies affecting the hip and pelvis include proximal hamstring tendinopathy (PHT), gluteal tendinopathy (greater trochanteric pain syndrome [GTPS]), and calcific tendinopathy (CT). Extracorporeal shockwave therapy (ESWT) is a noninvasive treatment described for the management of lower-extremity tendinopathies. Purpose : We sought to synthesize the evidence on ESWT used in the treatment of hip/pelvis tendinopathies, including protocols, outcomes, and safety. Methods : A comprehensive search of PubMed/Medline, EMBASE, and Cochrane Library databases was performed on November 1, 2024, for studies reporting ESWT data for hip/pelvis tendinopathies. Study design, population, and ESWT-related data (protocols, outcomes, and safety) were extracted. Results : Eighteen studies were included; 9 reported on GTPS, 7 on CT, and 5 on PHT. Most ESWT protocols (72% [n = 13]) implemented 3 to 4 weekly sessions and delivered 2000 to 3000 pulses/session (83% [n = 15]). Eleven studies used radial ESWT and 7 used focused ESWT. ESWT significantly improved pain and functional outcomes for GTPS, CT, and PHT in 17 level-I to level-V studies; only 1 level-V study showed no improvement. Six studies showed superior outcomes post-ESWT vs conservative treatment (PHT/GTPS), sham ESWT (GTPS), ultrasound therapy (GTPS/CT), or corticosteroid injection (GTPS). One study showed comparable outcomes between ESWT and eccentric exercise (GTPS). Two studies reported no outcome differences between radial ESWT and “minimal-dose” ESWT (GTPS) or combined ESWT (PHT). All studies assessing pain showed improvement from 0.5 to 27 months post-ESWT. Six of 18 studies reported adverse events, including increased pain and skin irritation (overall rate: 12% [n = 65/557]). Conclusions : The results of this systematic review suggest that ESWT may be safe and effective for hip/pelvis tendinopathies. Future research using validated outcome measures and ESWT parameters will aid in treatment optimization.
... Surgical treatment is also used, which may cause side effects and prolong the patient's recovery [4]. Focused shock wave therapy (fESWT) is increasingly used to treat the musculoskeletal system because it has been found that most of the effects of this therapy are related to mechanotransduction, which can lead to tissue healing by reducing pain, regulating inflammation and stem cell activity [5,6]. Available publications show that the effectiveness of therapy is most often assessed using surveys and questionnaires that indicate the patient's subjective pain sensations or functional assessment. ...
... Furthermore, the release of growth factors may contribute to the neo-vessel formation alongside increased cell growth and collagen production [95]. Finally, ESWT promotes tissue regeneration by stimulating osteoblasts while suppressing osteoclast activity [23], and it may also contribute to normalizing damaged blood vessels and joint metabolism [53]. ...
Purpose
Bone marrow lesions (BMLs) of the knee are a common magnetic resonance imaging finding and are present in a wide range of pathologies, including traumatic contusions and fractures, following cartilage surgery alterations, osteoarthritis, transient BMLs syndromes, subchondral insufficiency fractures of the knee and spontaneous osteonecrosis of the knee. Regardless of their aetiology, clinical management may prove challenging. This review focuses on the conservative treatment approaches to manage patients affected by knee BML, thanks to the contribution of field experts.
Methods
Experts from around the globe were involved in performing a review on the most used conservative treatment strategies to address BMLs, trying to summarize the available evidence from the most popular first‐line treatments while documenting their applications and results for the different BML aetiologies.
Results
Positive results were documented for unloading knee braces, external shockwave therapy, hyperbaric oxygen therapy, pulsed electromagnetic fields therapy and bisphosphonates. Nonetheless, the analysis of the scientific literature documented a scarce number of publications specifically addressing the knee joint, with even less evidence when it comes to the results for the different aetiologies of BMLs.
Conclusion
The management of BMLs is challenging, and many factors influence clinical and radiological outcomes. This paper summarized the evidence on conservative treatments for knee BMLs. Although showing promising results, conservative options still need to be fully investigated. Open questions to be addressed concern treatment duration, BML stage and overlapping with concomitant therapies. Further studies are needed to identify the best first‐line conservative approach or treatment combination based on each BML aetiology.
Level of Evidence
Level V: expert opinion.
... Mechano-transduction [30,31] is considered to be the basic mechanism of shock wave interaction with living tissues. Mechanical forces are required to press, stretch, and shear cell membranes to open ion channels and to express substances such as eNOS, BMP, VEGF, and substance P. ...
Background
Shock waves in medicine have gained enormous importance and have spread since 1980, and the first kidney stone was successfully fragmented in a patient in Munich. Meanwhile, the spectrum of medical applications of shock waves ranges from powerful fragmentation of kidney stones to diverse indications such as wound healing, chronic pelvic pain, spasticity, erectile dysfunction, and others, to neuro-stimulation in the context of Alzheimer’s disease. A comprehensive working mechanism for this diverse field of medical indications are still missing.
Objective
Investigation of the physical basis of the working mechanism of shock waves in medical applications.
Methods
We developed a model based on the mechanical forces generated by the momentum transfer at the acoustic interfaces of different layers of biological tissue. The generated forces are strong enough to crash brittle material and provide an adequate mechanical stimulus to activate mechano-transduction and mechano-sensory-transduction with nerve stimulation, thereby affecting the neural memory function of the central nervous system.
Results
The key to generating appropriate forces in the millisecond range is the mechanism of momentum transfer at the interfaces between tissue layers with different acoustic impedances. According to Newton´s laws of motion, a change in momentum (momentum transfer) generates force F = dP/dt. The inherent shear forces can stretch biological membranes to release biomolecules such as VEGF and NO. A most favourable feature of this mechanism is the selective effect on soft tissue interfaces and small tissue inhomogeneities to generate small forces in the range of few (≤ 10) Newton to stimulate tissue and nerve cells, while the same shock wave can generate forces ≥ 200 Newton and more on hard tissue interfaces such as bones or stones.
Conclusion
The mechanism of momentum transfer is the basis for mechano-transduction and mechano-sensory transduction. It offers the opportunity to stimulate peripheral nerves and modify the motor reflex patterns of “pathologic” reflexes by hyper stimulation. The new technique of transcranial pulse stimulation (TPS) may be based on direct stimulation and reactivation of neurons in the brain. Momentum transfer is the basic physical mechanism and the initiator for successive biological processes in medical shock wave therapy.
... LI-ESWT has shown beneficial renal effects in both pig and rat models, by inducing various angiogenic factors and reducing inflammation [17,18]. The shockwaves have a short duration of 10 μs and are characterized by a rapid positive pressure, followed by a period of negative pressure, ending with a return to ambient pressure, and work by forming cavity bubbles in the target tissue [19]. The subsequent stress induced by shockwaves leads to the activation of cell surface proteins, such as caveolin-1 and β1-integrin, which act as mechanotransducers [20]. ...
Purpose
Low-intensity extracorporeal shockwave therapy (LI-ESWT) is a potential novel treatment against diabetic kidney disease (DKD). The present study investigates the longer term effects of LI-ESWT on kidney function in patients with DKD.
Methods
This matched cohort study included 28 patients with DKD, who received six sessions of LI-ESWT. Patients were matched 1:5 with patients from the Funen Diabetes Database. Multivariable adjusted eGFR and ACR were analyzed using multilevel mixed-effects linear regression. The primary outcomes were ACR and eGFR measured at 3, 6, 12, and 18 month follow-up. Secondary analyses with patients stratified for sex, age, baseline eGFR, and baseline ACR were made for the multivariable adjusted values of eGFR and ACR.
Results
No significant difference in multivariable adjusted ACR or eGFR was found at 18 months. The intervention group showed a non-significant decrease in adjusted eGFR (1.83 mL/min/1.73 m² lower, p = 0.15) and ACR (14%, p = 0,56). Stratified results revealed lower eGFR in patients > 60 years 3.64 mL/min/1.73 m², p = 0.03) and those with baseline ACR ≤ 300 mg/g (3.64 mL/min/1.73, p = 0.007).
Conclusion
LI-ESWT did not demonstrate overall statistically significant effects on eGFR and ACR at 3, 6, 12, or 18 months. However, secondary analyses suggest possible effects in certain subgroups. Clinical studies with larger samples are needed to clarify the efficacy of LI-ESWT in specific DKD patient subgroups.
Trial Registration The trial was prospectively registered July 31, 2015, at ClinicalTrials.gov with registration number NCT02515461.
... Extracorporeal shock wave therapy (ESWT) is a mechanical treatment that utilizes pulsed pressure waves to alter the chemical environment of the injury site [12]. This approach helps reduce local in ammation, reverse tissue damage, and promote tendon remodeling [13]. ...
Background In recent years, numerous meta-analyses have been published on the effectiveness of ESWT in treating various tendinopathies. However, due to limitations such as the small number of included studies, it remains unclear whether ESWT is definitively effective for all types of tendinopathies and what its comparative value is relative to other conservative treatments. The objective of this meta-analysis is to compare ESWT with other conservative treatments to determine its effectiveness in alleviating pain and improving the severity of tendinopathies. Additionally, through network meta-analysis, we aim to compare the efficacy of ESWT and other conservative treatments across different types of tendinopathies. This will help establish the value of ESWT in each type of tendinopathy, providing a theoretical basis for clinical decision-making regarding ESWT treatment for various tendinopathies. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, and Cochrane Library databases along with other databases were searched to identify relevant randomized controlled trials (RCTs). The quality of the selected studies was evaluated using risk of bias assessments, and the data were extracted. Network meta-analysis was performed using random effects models to evaluate the effects of different treatment modalities on reducing pain and improving functional outcomes. reduction and functional improvement. The evidence of the included studies was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Results This study included 65 publications from 2002 to 2024, with a total sample size of 3,921 cases. The included studies covered five types of tendinopathies: lateral epicondylitis, rotator cuff tendinopathy, Achilles tendinopathy, greater trochanteric pain syndrome, and patellar tendinopathy. Through pairwise subgroup meta-analyses, we obtained the following representative results: for VAS in lateral epicondylitis, ESWT vs US, SMD − 2.53 [95% CI -3.03 to -2.03], I²=64.7%; ESWT vs PLACEBO, SMD − 0.53 [95% CI -0.76 to -0.30], I²=39.0%; for VAS in Achilles tendinopathy, ESWT vs PLACEBO, SMD − 0.49 [95% CI -0.83 to -0.16], I²=0; for VISA-P in patellar tendinopathy, ESWT vs PLACEBO, SMD − 0.15 [95% CI -0.42 to 0.12], I²=0; for VAS in rotator cuff tendinopathy, ESWT vs PLACEBO, SMD − 1.25 [95% CI -1.61 to -0.89], I²=89.1%; for GTPS, ESWT vs EX, SMD − 0.41 [95% CI -0.70 to -0.11], I²=10.2%. In the network meta-analysis, the following representative results were obtained: in LE, ESWT ranked second in SUCRA for improving VAS and PRTEE, with no significant difference from the first rank (ESWT vs PDRN, MD 0.44 [95% CI -2.76 to 3.64]; ESWT vs KT, MD 0.39 [95% CI -0.88 to 1.66]); in RCT, ESWT ranked second in SUCRA for improving SPADI, with no significant difference from the first rank (ESWT vs EX, MD 0.15 [95% CI -0.24 to 0.55]); in AT, ESWT ranked second in SUCRA for improving VAS, with a significant difference from the first rank (ESWT vs LT, MD 2.55 [95% CI 1.86 to 3.24]). Conclusions Current limited evidence suggests that, compared to control groups, ESWT effectively improves pain and tendinopathy severity indicators in various tendinopathies except for patellar tendinopathy. However, its efficacy may vary across different tendinopathy types. Compared to other conservative treatments, ESWT holds a favorable position in treating lateral epicondylitis (LE), Achilles tendinopathy (AT), and rotator cuff tendinopathy (RCT). Notably, we found that ESWT does not show a significant therapeutic effect over placebo in the treatment of patellar tendinopathy.
... These results suggest that ESWT has not only local effects on bone strength, bone mineral density (BMD), and bone volume but also systemic effects on osteoporosis. In addition, ESWT has been reported to stimulate tissue regeneration through mechanotransduction [31]. Therefore, ESWT has the potential to be a promising noninvasive therapy for osteoporosis by promoting new bone formation and improving bone strength and density, not only locally but also systemically. ...
Background: Osteoporosis (OP) is a chronic inflammatory bone disease characterized by reduced bone structure and strength, leading to increased fracture risk. Effective therapies targeting both bone and cartilage are limited. This study compared the therapeutic effects of extracorporeal shockwave therapy (ESWT), bisphosphonate (Aclasta), and human Wharton jelly-derived mesenchymal stem cells (WJMSCs) in a rat model of OP. Methods: Female rats were assigned to four groups: Sham (no surgery or treatment), OP (bilateral ovariectomy, OVX), ESWT (OVX + ESWT on both tibias at 0.25 mJ/mm², 1500 impulses per tibia), Aclasta (OVX + zoledronic acid 0.1 mg/kg via tail vein injection), and WJMSC (OVX + 2 × 10⁶ WJMSCs). Pathological changes, bone microarchitecture (by micro-CT), serum cytokines (by ELISA), and tissue-specific molecular markers (by immunohistochemistry) were evaluated. Results: All treatments improved bone density, preserved cartilage, and modulated cytokines (IL31, IL33, VEGF, and BMP2), with Aclasta showing the greatest improvements in bone parameters and cartilage preservation. ESWT and WJMSC also demonstrated significant effects, with ESWT highlighting non-invasive chondroprotective potential. Conclusions: Aclasta provided the best overall therapeutic response, particularly in bone regeneration. However, ESWT and WJMSC also showed comparable chondroprotective effects. ESWT emerges as a promising non-invasive alternative for OP management when pharmacological or cell-based therapies are not feasible.
... Furthermore, d' Agostino et al. (2015) discovered that ESWT can influence mechano-transduction, aiding the body's signaling pathways by converting mechanical stimuli into biochemical signals and consequently affecting the intracellular matrix, nucleus, and cell mitochondria. However, myogenic factor 5 expression was observed in the stellate cells isolated from spine muscles post-ESWT compared to controls [39]. Mattyasovszky et al. (2018) assessed ESWT as a biological therapeutic tool and reported myogenic stimulation and muscle building in the myoblast cells of the mice receiving low-intensity ESWT. ...
Introduction: Myofascial pain syndrome is a common musculoskeletal injury, especially among athletes, typically treated with symptomatic invasive and non-invasive methods. This study compares the effects of massage guns and radial extracorporeal shock wave therapies on myofascial pain syndrome symptoms in amateur athletes. Materials and Methods: In this clinical trial, 45 amateur athletes (18-30 years old) were recruited, who were randomly assigned to 15-member groups of shock wave, massage gun, and control (routine treatment included electrotherapy and stretching, which was applied on three groups). After initial evaluations of the pain intensity, pain pressure threshold (PPT), isometric muscle strength, and range of motion (ROM), the patients received single-session treatment and were immediately reassessed. Results: The results showed pain relief and improved PPT following shock wave plus routine treatment (P=0.03). The control group had less pain, while pain intensity and PPT did not change. The variables were not significantly different between the groups (P=0.12). Shock wave along with routine treatment increased plantar flexion ROM (P=0.00), unlike the massage gun. Additionally, dorsiflexion ROM (P=0.63) and maximal isometric gastrocnemius muscle strength (P=0.95) remained unchanged in all groups. Conclusion: One session of massage gun therapy immediately reduced gastrocnemius muscle pain, while it failed to change PPT, maximal isometric gastrocnemius muscle strength, or dorsiflexion and plantar flexion ROM. However, shock wave therapy immediately increased plantar flexion ROM and PPT, and reduced pain intensity. These modalities led to limited changes, suggesting the need for repeated sessions and supplementary treatments.
... Comprehensive understanding is crucial for preventing or treating fibrosis and understanding the effects of shockwaves. SWT, defined as mechanotherapy, dynamically regulates inflammation, proliferation, activation and differentiation in various tissues impacting cells, such as fibroblasts, growth factors, collagen, macrophages and keratinocytes [4,5,50]. ...
Fibrosis is characterized by scarring and hardening of tissues and organs. It can affect every organ system, and so could result in organ failure due to the accumulation of extracellular matrix proteins. Previous studies suggest that mechanical forces (such as shockwave therapy, SWT) initiate a process of mechanotransduction and thus could regulate fibrosis. Nevertheless, it is largely unexamined which pathways are exactly involved in the application of SWT and can regulate fibrosis. The present article seeks to elucidate the underlying effect of SWT on fibrosis. Evidence shows that SWT activates macrophage activity, fibroblast activity, collagen amount and orientation and apoptosis, which ultimately lead to an adaptation of inflammation, proliferation, angiogenesis and apoptosis. The included articles reveal that other proteins and pathways can be activated depending on the energy levels and frequency of SWT. These findings demonstrate that SWT has beneficial effects on fibrosis by influencing the proteins and pathways. Based on these data, which highlights the underlying mechanisms, we can make preliminary conclusions about the treatment modalities of SWT in scar formation, such as the energy levels and frequencies that are necessary to prevent or treat fibrotic tissue.
... In individuals with ED, LiSWT to the penis has been hypothesized to induce numerous downstream biochemical signaling events within the erectile tissue through the process of mechanotransduction, as supported by animal studies (56)(57)(58). In these animal studies, it was observed that the ratio of cavernosal smooth muscle to connective tissue increased (59). ...
Background
Electrohydraulic shockwave devices have been Food and Drug Administration-cleared for improved blood flow and connective tissue activation and have been used to treat erectile dysfunction (ED). In this study, the main focus was to evaluate improvement in erectile tissue quality after low intensity shockwave therapy (LiSWT).
Methods
A single-blind, sham-controlled, randomized, prospective study, was performed in men with ED naïve to shockwave or radial ballistic pressure wave therapy. Participants were randomized 1:2 to simulated (sham) or active LiSWT treatment. After simulated treatments, participants in the Sham Arm were converted to active LiSWT, while participants initially in the Active Treatment Arm received no further treatment. Assessments were performed at baseline and two follow-up visits. Subjective parameters of erectile function (EF) were assessed by total and EF domain scores of the International Index of Erectile Function (IIEF) and sexual encounter profile (SEP). Objective parameters of penile erection were measurements of hypoechoic areas in images obtained by grayscale ultrasound (GUS) with high resolution 15.4 MHz probe and cavernosal artery peak systolic velocity (PSV) and end diastolic velocity (EDV) by color duplex Doppler ultrasound (DUS). Outcome measures for erectile and urinary function were also obtained.
Results
Simulated LiSWT did not significantly change any assessment parameter. Sham Arm participants who converted to active LiSWT had significantly increased mean IIEF total (P=0.02) and IIEF-EF scores that approached statistical significance (P=0.06), relative to baseline. Similarly, at the end of the study, Active Treatment Arm participants had significantly increased mean IIEF total (P=0.02) and IIEF-EF scores that approached statistical significance (P=0.07), relative to baseline. Additionally, at the end of the study, SEP3 success rates (erection lasting long enough for successful intercourse) approached statistical significance when Sham Arm participants were converted to active LiSWT (P=0.08) and reached statistical significance in the Active Treatment Arm (P=0.049). GUS assessments by visual grading were significantly correlated to IIEF-EF score (P=0.002) and were significantly increased relative to baseline in the Active Treatment Arm at follow-up Assessment 1 (P=0.03) and Assessment 2 (P=0.04). The greatest reduction in hypoechoic area after LiSWT occurred in the proximal penile shaft. EDV was also significantly reduced in the Active Treatment Arm at follow-up Assessment 1 (P=0.04) and Assessment 2 (P=0.04). LiSWT also resulted in improved prostate symptom scores, approaching significance in the Active Treatment Arm (P=0.055) with no changes in prostate-specific antigen. Treatment-related adverse events were limited and transient.
Conclusions
In this prospective trial, LiSWT was safe and efficacious for erectile symptoms using GUS imaging as a novel, non-invasive method to assess improvements in corporal veno-occlusive function. Improved veno-occlusion and reduced hypoechoic area demonstrated by GUS imaging suggest that LiSWT decreases connective tissue content in penile erectile tissue. Lower urinary tract symptoms also improved with LiSWT.
Trial Registration
NCT06600893 on clinicaltrials.gov.
... ,16,40,41 . Shockwave alters the morphological ...
Persistent symptoms of lateral epicondylitis prompt patients to seek effective conservative treatment. The study aimed to determine the effects of focused shock wave (FSWT) and ultrasound therapies for lateral epicondylitis. Sixty patients with tennis elbow were randomly divided into three equal groups: A, B, and C. Group A received a total of 3 FSWT sessions, with 7 days between treatments; Group B received ultrasound therapy in 10 sessions over 2 weeks, while patients in Group C were treated with placebo ultrasound. All patients were also given deep friction massage. Before the start of therapy, and at 1, 3, 6, and 12 weeks after its completion, pain intensity and function of the affected upper limb were assessed in all patients. Wrist extensor and flexor strength and grip strength were measured in the affected and unaffected limb. Significant reductions in pain and significant improvements in the function of the affected limb compared to baseline values were observed in all study groups at 6 and 12 weeks after the completion of therapy. Analysis of percentage changes in these variables showed significant differences between Groups A and B in favor of Group A. The strength of wrist extensors and grip strength of the affected limb at 6 and 12 weeks after treatment completion was significantly higher in Groups A and B compared to pre-therapy values. However, there were no statistically significant differences between the groups regarding percentage changes in muscle strength in the affected limb. Pain reduction and function improvement in patients with lateral epicondylitis were significantly greater after FSWT (0.2 mJ/mm² / 4 Hz / 2000 shocks) than after sonotherapy (3 MHz / 0.5 W/cm² / 20%). Increases in wrist extensor strength and grip strength of the affected limb were comparable after both therapies. Given the greater therapeutic effect in the subjective evaluation, we recommend a combination therapy of FSWT with deep friction massage.
Trial registration The trial was prospectively registered in the ISRCTN registry (no. ISRCTN11907358 registration date 30.07.2020).
... Given the limitations of nonoperative management, other noninvasive modalities have gained interest. Extracorporeal shockwave therapy (ESWT) is a noninvasive treatment modality, not approved by the US Food and Drug Administration, that is often indicated after failure of first-line treatment modalities for AT. 13 ESWT produces focused longitudinal sound waves that create a biological cascade via mechanotransduction, inducing local neovascularization, cell proliferation, calcific resorption, downregulation of metalloproteinases, and inhibition of substance P. 5,28 ESWT has been used in various sports medicine pathologies including plantar fasciitis, peroneal tendinopathy, lateral epicondylitis, patellar tendinopathy, and adductor tendinopathy. 20 In recent years, studies have been conducted to investigate the role of ESWT in AT, with good outcomes reported at final follow-up. ...
Background
Extracorporeal shockwave therapy (ESWT) is a noninvasive treatment modality that is used in the treatment of chronic Achilles tendinopathy (AT).
Purposes
To (1) retrospectively assess outcomes after ESWT for both noninsertional AT (NAT) and insertional AT (IAT) at >1-year follow-up and (2) identify potential predictors of outcomes.
Study Design
Cohort study; Level of evidence, 3.
Methods
Chart review was conducted to identify patients who underwent ESWT for AT with a minimum of 1-year follow-up. Data collected and assessed included patient demographic characteristics, pathological characteristics including the location of AT (NAT or IAT), presence of a Haglund deformity, and severity of tendon degeneration on magnetic resonance imaging (MRI), in addition to treatment characteristics including number of sessions and intensity of ESWT. The Victorian Institute of Sports Assessment–Achilles (VISA-A) and visual analog scale (VAS) pain scores were obtained before ESWT, 6 months after ESWT, and at final follow-up. Failures were also recorded, which were defined as no improvement in VISA-A or VAS scores or need for surgical intervention. Linear regression was performed to identify potential predictors of inferior subjective clinical outcomes and failures. Survival analysis was conducted using Kaplan-Meier curves.
Results
The study included 52 patients with IAT and 34 patients with NAT. The mean follow-up in the NAT cohort was 22.3 ± 10.2 months and the mean follow-up in the IAT cohort was 26.8 ± 15.8 months. Improvements in VISA-A and VAS scores were observed in the NAT cohort at 6-month follow-up and at final follow-up (P < .05). Improvements in VISA-A and VAS scores were recorded in the IAT cohort at 6-month follow-up, which subsequently deteriorated at final follow-up. In the NAT cohort, the failure rate at 6-month follow-up was 11.8%, which increased to 29.4% at final follow-up. In the IAT cohort, the failure rate at 6-month follow-up was 32.7%, which increased to 59.6% at final follow-up. Predictors of inferior subjective clinical outcomes and failures in the NAT cohort included pre-ESWT subjective clinical score, male sex, presence of a cardiovascular risk factor, and more severe MRI grading of tendinopathy. Predictors of inferior subjective clinical outcomes and failures in the IAT cohort included pre-ESWT subjective clinical score and more severe MRI grading of tendinopathy.
Conclusion
Superior subjective clinical outcomes together with a lower failure rate were maintained for >1 year in the NAT cohort compared with the IAT cohort, calling into question the long-term benefit of ESWT for patients with IAT.
... Effects include enhanced neovascularity, accelerated growth factor release, selective neural inhibition, and inhibition of molecules that have a role in inflammation. 10,11 These findings suggest that ESWT could potentially have a positive effect on the healing of chronic tendinosis which is characterized by hypovascularity. ...
... La interacción de OCH con la materia es un campo amplio y, aunque se ha avanzado en la comprensión de los fenómenos involucrados, aún quedan preguntas por responder 1 . Uno de los principales fenómenos relacionados con la mecanotransducción, es el crecimiento y colapso de microburbujas después del paso de una OCH, denominado cavitación acústica 10 . El colapso es tan violento que genera chorros de fluido de alta velocidad (microjets) y OCH secundarias que producen esfuerzos en los tejidos, aumentando la circulación y el metabolismo, así como la permeabilidad celular 1 . ...
Introducción: Las aplicaciones biomédicas de las ondas de choque se han establecido para el tratamiento de varios padecimientos. Objetivo: Evaluar la efectividad de las ondas de choque extracorpóreas según la presión y la cantidad de ondas aplicadas, para estimular la proliferación de un cultivo de odontoblastos y células troncales pulpares humanas. Material y métodos: Estudio experimental in vitro, prospectivo y comparativo. Se inocularon 6×105 células/mL de células óseas humanas y pulpares, a las que se les aplicaron diferentes dosis de ondas de choque, formándose aleatoriamente ocho grupos por tipo celular. Resultados: La cantidad de ondas de choque y la presión del pulso positivo de las mismas influyen en la viabilidad celular. Al aplicar a osteoblastos 400 ondas de choque con una presión de aproximadamente 22 MPa, se obtuvo un incremento del 50% en la viabilidad celular, a las 48 horas postratamiento. Conclusiones: El uso de presiones bajas y cantidades de ondas de choque altas aumentan la actividad celular.
... Considering the mechanisms of action of eSWT, Simplicio et al. [23] indicates vascularization, protein biosynthesis, cell proliferation, neuroprotection and chondroprotection. d'Angelo et al. [24] characterize eSWT as a form of mechanotransduction and foresee exciting and beneficial applications in regenerative medicine, tissue engineering, and cell therapies. ...
Background: Injury of the spinal cord causes motor and sensory dysfunction as well as pathological reflexes, leading to paraplegia or tetraplegia. The sequelae of traumatic spinal cord injury (SCI) are a significant burden and impact on healthcare systems. Despite constant progress in medicine, traumatic SCI still remains irreversible. To date, no satisfying treatment that can enable neuronal regeneration and recovery of function at the damaged level has been found. Hundreds of experiments have been conducted on various possibilities of influencing spinal regeneration; some of them have yielded promising results, but unfortunately, the successes obtained in experimental animals have not translated into humans. Methods: This narrative review article presents the application of extracorporeal shock wave therapy (eSWT) in patients with SCI. The article has been divided into parts: 1) use of extracorporeal shock wave therapy for regeneration of the spinal cord after traumatic spinal cord injury; 2) application of extracorporeal shock wave therapy in spasticity after spinal cord injury. In both cases, the hypotheses of possible mechanisms of action will be described. Results and conclusions: A small number of clinical trials have demonstrated the potential of eSWT to influence the regeneration of the spine, as an innovative, safe, and cost-effective treatment option for patients with SCI. Some reports have shown that eSWT can improve spasticity, walking ability, urological function, quality of life, and independence in daily life.
... ESWT can trigger the extracellular matrix and cytoskeleton by stretching channels, serving as a mechanical force source [20]. The initiation of this process stimulates the proliferation, migration, and differentiation of stem cells, which are essential for the healing and regeneration of tissues [21]. ESWT has become increasingly popular as a treatment choice for a range of musculoskeletal conditions [22], including plantar fasciitis, tennis elbow [23], and nonunion [24], due to its positive impacts. ...
In the last ten years, stem cell (SC) therapy has been extensively used to treat a range of conditions such as degenerative illnesses, ischemia-related organ dysfunction, diabetes, and neurological disorders. However, the clinical application of these therapies is limited due to the poor survival and differentiation potential of stem cells (SCs). Extracorporeal shock wave therapy (ESWT), as a non-invasive therapy, has shown great application potential in enhancing the proliferation, differentiation, migration, and recruitment of stem cells, offering new possibilities for utilizing ESWT in conjunction with stem cells for the treatment of different systemic conditions. The review provides a detailed overview of the advances in using ESWT with SCs to treat musculoskeletal, cardiovascular, genitourinary, and nervous system conditions, suggesting that ESWT is a promising strategy for enhancing the efficacy of SC therapy for various diseases.
... According to previous studies, ESWT for tendonitis is associated with pain relief, tissue repair, and calcific destruction (17,18). ESWT produces mechanotransduction effects, decreases the concentration of proinflammatory factors, activates downstream inhibitory systems, and promotes the associated intracellular chemical reactions and protein synthesis (19)(20)(21). Mechanical stimulation reduces the expression of matrix metalloproteinases and interleukins associated with tendonitis (22). ESWT also increases the material conversion rate of the extracellular matrix and induces neovascularization (23), which promotes collagen synthesis for tendon tissue repair. ...
Objective
This study synthesized the highest level of evidence to analyse the effectiveness and safety of using extracorporeal shock wave therapy (ESWT) to treat upper limb tendonitis, which was unknown.
Design
We conducted a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) in PubMed, Embase, Web of Science, Medline, and the Cochrane Library.
Methods
Two researchers performed the screening, data extraction, literature quality assessment, and heterogeneity analysis of the searched RCTs.
Results
The main types of morbidity included rotator cuff tendonitis, lateral epicondylitis, finger tendonitis, and long bicipital tendonitis. The results of the meta-analysis showed that ESWT was effective in relieving pain in all four types of tendonitis. In addition, ESWT was more effective in relieving pain in patients with upper limb tendonitis than placebo at the 3- and 6-month follow-ups, especially with radial ESWT (RESWT). Data analysis of the forest plot showed that the experimental group with ESWT as an intervention had a significant improvement in function in patients with rotator cuff tendonitis at the 3-month follow-up. However, subgroup analysis showed that low-energy ESWT was effective in improving function in patients with calcified and non-calcified rotator cuff tendonitis, whereas it was not effective in relieving pain.
Conclusion
ESWT can effectively improve the functional activity in patients with rotator cuff tendonitis and may produce positive analgesic effects in patients with upper limb tendonitis. The incidence of adverse effects is low.
Systematic Review Registration
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023403594, identifier: PROSPERO, CRD42023403594.
... The complex interplay between genetic and environmental factors, including free radicals and compromised DNA repair, encompasses the carcinogenic potential that can lead to cancer. [38][39][40][41] Based on previously reported results, 36,42,43 we posit that, in the absence of adverse effects, the angiogenic and proliferative responses induced by Li-ESWT within clinical treatment parameters are unlikely to contribute to the development of prostate tumors or other pathologies. Hence, this study expands beyond the discussion of the mechano-biological effects of Li-ESWT in the context of prostate cancer development. ...
Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model ( n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [ γ -H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo . This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.
... Considering the mechanisms of action of eSWT, Simplicio et al. indicates vascularization, protein biosynthesis, cell proliferation, neuroprotection and chondroprotection [23]. Describing eSWT as mechanotransduction d`Angelo et al. foresee new interesting and promising applications in the fields of regenerative medicine, tissue engineering and cell therapies [24]. Guo et al. published a review on the possibility of regeneration and repair of neurological disorders using the eSWT method. ...
Background: Injury of the spinal cord causes motor and sensory dysfunction, and pathological reflexes, leading to paraplegia or tetraplegia. The sequelae of traumatic spinal cord injury (SCI) is a significant burden and impact on healthcare systems. Despite constant progress in medicine, traumatic SCI still remains irreversible. Till now, no satisfying treatment that can enable neuronal regeneration and recovery of function at the damaged level has been found. Hundreds of experiments have been conducted on various possibilities of influencing spinal regeneration, some of them have yielded promising results, but unfortunately, the successes obtained in experimental animals have not translated into humans. Methods: This narrative review article presents the application of Extracorporeal Shock Wave Therapy (eSWT) in Spinal Cord Injury. The article has been divided into parts: 1. Use of extracorporeal Shock Wave Therapy for regeneration of the spinal cord after traumatic Spinal Cord Injury. 2. Application of extracorporeal Shock Wave Therapy in spasticity after Spinal Cord Injury. In both cases, the hypotheses of possible mechanisms of action will be described. Results and conclusions: A small number of clinical trials have demonstrated the potential of eSWT to influence the regeneration of the spine, as an innovative, safe, and cost-effective treatment option for patients with SCI. Some reports have shown that eSWT can improve spasticity, walking ability, urological function, quality of life, and independence in daily life.
... The observed pain reduction is thought to be due to intracellular changes following the conversion of mechanical extracorporeal shock waves into biochemical signals [17]. It has been reported that pulsatile stimulation of pain receptors (nociceptors) by ESWT partially or completely disrupts the transmission of potential pain stimuli; ESWT overstimulates nociceptors beyond their sensitivity thresholds, resulting in numbing of sensory neurons to noxious stimuli and thus decreases pain perception [24,25]. The decrease in treatment efficacy in obese patients may be due to the fact that skin and subcutaneous tissue density in the perineum increases the distance to the prostate and thus limits the mechanotherapeutic and immunomodulatory [26] effect of ESWT on the prostate. ...
It was aimed to investigate the effect of perineal extracorporeal shock wave therapy (ESWT) applied to chronic prostatitis (CP) patients on prostatitis symptoms and sexual functions, based on age and body mass index (BMI) parameters. Forty male patients aged 18 and over who underwent ESWT for CP were included in the study. The age and BMI of the patients were recorded. Patients were evaluated with the International Erectile Function Form and the International Health Institute – Chronic Prostatitis Symptom Index before and 3 months after ESWT. Prostatitis symptoms and sexual function values of the patients were analyzed, as well as age and BMI parameters. The average age of the patients was 31 (±7.88) years and the average BMI was 25.27 (±4.89) kg/m2. When all patients were evaluated, ESWT; it created a statistically significant positive difference in pain and quality of life scores on the CP side. ESWT; created a statistically significant positive difference in erectile function and sexual and general satisfaction scores. When looking at ESWT effectiveness according to BMI values; erectile function, orgasmic function, and sexual and general satisfaction scores increased more in normal-weight patients than in obese patients. In addition, a greater decrease in prostatitis pain score was observed after treatment in normal-weight patients compared to obese patients. ESWT treatment is an effective method for CP patients, especially in relieving pain. The erectile function also increases sexual and general satisfaction. In obese people, its contribution to both pain palliation and erectile function is limited. Prospective, randomized, multicenter, and high-participation studies are needed.
... The Piezo1 channel in the cellular membrane induces Ca 2+ influx upon opening in response to various mechanical stimuli, including matrix stiffness, shear stress, radial pressure, membrane stretching, and compression [32]. Both US and shockwave therapies activate Piezo1 [33][34][35]. Activated Piezo1 participates in diverse signaling pathways in inflammation, cell proliferation, and fibrosis [36]. Furthermore, Piezo1 promotes M2 macrophage polarization [37], a process essential for anti-inflammatory responses and tissue repair [38][39][40]. ...
The dermal–epidermal junction (DEJ) is essential for maintaining skin structural integrity and regulating cell survival and proliferation. Thus, DEJ rejuvenation is key for skin revitalization, particularly in age-related DEJ deterioration. Radiofrequency (RF) treatment, known for its ability to enhance collagen fiber production through thermal mechanisms and increase heat shock protein (HSP) expression, has emerged as a promising method for skin rejuvenation. Additionally, RF activates Piezo1, an ion channel implicated in macrophage polarization toward an M2 phenotype and enhanced TGF-β production. This study investigated the impact of RF treatment on HSP47 and HSP90 expression, known stimulators of DEJ protein expression. Furthermore, using in vitro and aged animal skin models, we assessed whether RF-induced Piezo1 activation and the subsequent M2 polarization could counter age-related DEJ changes. The RF treatment of H2O2-induced senescent keratinocytes upregulated the expression of HSP47, HSP90, TGF-β, and DEJ proteins, including collagen XVII. Similarly, the RF treatment of senescent macrophages increased Piezo1 and CD206 (M2 marker) expression. Conditioned media from RF-treated senescent macrophages enhanced the expression of TGF-β and DEJ proteins, such as nidogen and collagen IV, in senescent fibroblasts. In aged animal skin, RF treatment increased the expression of HSP47, HSP90, Piezo1, markers associated with M2 polarization, IL-10, and TGF-β. Additionally, RF treatment enhanced DEJ protein expression. Moreover, RF reduced lamina densa replication, disrupted lesions, promoted hemidesmosome formation, and increased epidermal thickness. Overall, RF treatment effectively enhanced DEJ protein expression and mitigated age-related DEJ structural changes by increasing HSP levels and activating Piezo1.
... The mechanical forces generated by ESWT are believed to activate various cellular signaling pathways, leading to increased production of growth factors, cytokines, and other molecules involved in tissue repair and regeneration as mechanotransduction phenomena. 27 Additionally, ESWT is thought to modulate inflammation, enhance neovascularization, and promote the recruitment of cells proliferation to the injured site. The mechanical impact of shock waves on cellular structures may trigger cellular processes that contribute to tissue healing, making ESWT a promising therapeutic approach for conditions ranging from musculoskeletal injuries to chronic wound healing. ...
Purpose
Extracorporeal shock wave therapy (ESWT) is a beneficial adjunct modality for chronic wounds. Limited research has been conducted on pressure ulcers (PUs), while the majority of studies have focused on diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). This study aimed to evaluate the short-term effects of radial ESWT in older adults with chronic wounds.
Patients and Methods
This study involved a total of 31 wounds: PUs (n=22), VLUs (n=7), and DFUs (n=2). A single radial ESWT was performed with 300 + 100 shocks per cm², pressure of 2.5 bar, energy of 0.15 mJ/mm², and frequency of 5 Hz. Assessments using digital planimetry and clinical methods, utilizing the Wound Bed Score (WBS) and the Bates-Jansen Wound Assessment Tool (BWAT) were performed before the radial ESWT application (M0) and one week after (M1).
Results
A significant wound decrease in planimetry was noted (pre-ESWT vs post-ESWT), with wound area from 9.4 cm² to 6.2 cm², length from 6.4 cm to 3.9 cm, and width from 2.8 cm to 2.1 cm (p<0.001). Additionally, a substantial clinical improvement was noted in both the WBS with a 31.25% increase and the BWAT with a 20.00% increase (p<0.001). It was also found a significant correlation between the planimetric and clinical outcomes for both tools: WBS (r=−0.446, p=0.012) and BWAT (r=0.327, p=0.073).
Conclusion
The ESWT application yields substantial immediate clinical effects that support the healing of chronic wounds in older adults. Even a single ESWT session can prove to be clinically effective and beneficial in the management of chronic wounds.
... 17 Histological evaluation of bone tissue after the application of focused waves ruled out the presence of "microfractures" when therapeutic doses are used. 18 The purely mechanical effect is only effective in the case of the destruction of calculi, which are inert mineral accumulations. In living tissues, the mechanism of action is biological, based on the phenomenon of mechanotransduction. 12,13,19 Cells and the extracellular matrix are influenced by mechanical stimuli. ...
The advent of renal lithotripsy in the 1980s had a disruptive effect on the treatment of kidney stones. The discovery of the biological effects of shock waves quickly expanded the use of this therapeutic method to the field of Orthopedics and Traumatology. Although the topic has advanced significantly in recent years, there are still many questions and confusions in our specialty's environment, particularly among professionals who are not directly involved in the field. The objective of this presentation is to provide a scientific analysis of the points of controversy and the most frequent doubts. Level of Evidence: V Mitos, verdades, dudas y confusiones sobre las ondas de choque y su rol en la enfermedad musculoes-quelética rEsuMEn El advenimiento de la litotricia renal en la década de los 80 tuvo un efecto disruptivo en el tratamiento de los cálculos renales. El descubrimiento de los efectos biológicos de las ondas de choque expandió rápidamente el uso de este método terapéutico al cam-po de la Ortopedia y Traumatología. Si bien, en los últimos años, ha tenido un amplio desarrollo, persisten muchas confusiones y dudas en el ambiente de nuestra especialidad, sobre todo entre los profesionales que no están directamente involucrados en el tema. El objetivo de esta presentación es hacer un análisis de los puntos de controversia y las dudas más frecuentes, basado en la bibliografía científica. Palabras clave: Ondas de choque; ondas radiales de presión; mecanotransducción. nivel de Evidencia: V
... Aseptic inflammation is not sensitive to antibiotic drugs, and the clinical effect of antibiotic treatment alone is limited. Ultrasound's high-frequency mechanical vibrations can generate micro-massage within the extremely small cell structures, facilitating the uptake and dispersion of inflammation within the fallopian tubes [18,19] . This study sought to evaluate and compare the clinical efficacy of utilizing the combined treatment of clindamycin and ultrasound with the single treatment and inflammation. ...
Mastitis, an inflammation of mammary tissue frequently associated with infection, is a prevalent disease among dairy animals. Bacterial intra-mammary infection is identified as a primary cause of bovine mastitis (BM). In dairy cattle, antimicrobials are used for mastitis treatment during the lactating phase and for dry cow therapy. Although self-curing can occur, the success of mastitis treatment depends on several factors, including the type of bacteria responsible for the infection, the effectiveness of the administered antibiotics, and the host's overall immune response. Moreover, the growing resistance of microorganisms to antibiotics has restricted the available treatment options for managing intramammary infections. In addition, the utilization of critically essential antimicrobials in animals raised for food production may elevate the risk of human infections that are challenging to treat. Therefore, it is crucial to have alternative treatments with equivalent or superior effectiveness as part of any stewardship program. These may include the application of nanotechnology, stem cell technology, photodynamic and laser radiation or the use of traditional herbal medical plants, nutraceuticals, antibacterial peptides, bacteriocins, antibodies therapy, bacteriophages, phage lysins, and probiotics as alternatives to antibiotics. This review aims to discuss the potential of vaccination as an indirect strategy, along with nanotechnology, probiotics, stem cell therapy, antimicrobial peptides, photodynamic therapy, laser irradiation, and antibody treatments as direct approaches. These approaches are examined as possible alternative therapeutic options to antibiotic treatment for BM.
Physical therapy modalities play an essential role in the treatment of osteonecrosis and bone marrow edema. In addition to an accurate diagnosis, it is essential to understand the pathogenesis of the disease in order to define relevant physiological, cellular and biochemical targets. After careful consideration of efficacy and side effects, these therapies can be used both as adjunctive measures and as stand-alone treatments to prevent disease progression. In particular, shock wave and magnetic field therapies show promising results both clinically and in ongoing trials. In addition, in the acute phase, a targeted unloading phase may be helpful to reduce mechanical pressure on bone tissue. Interdisciplinary treatment planning and patient compliance are of similar importance.
Despite the massive efforts of modern medicine to stop the evolution of Alzheimer’s disease (AD), it affects an increasing number of people, changing individual lives and imposing itself as a burden on families and the health systems. Considering that the vast majority of conventional drug therapies did not lead to the expected results, this review will discuss the newly developing therapies as an alternative in the effort to stop or slow AD. Focused Ultrasound (FUS) and its derived Transcranial Pulse Stimulation (TPS) are non-invasive therapeutic approaches. Singly or as an applied technique to change the permeability of the blood–brain–barrier (BBB), FUS and TPS have demonstrated the benefits of use in treating AD in animal and human studies. Adipose-derived stem Cells (ADSCs), gene therapy, and many other alternative methods (diet, sleep pattern, physical exercise, nanoparticle delivery) are also new potential treatments since multimodal approaches represent the modern trend in this disorder research therapies.
Background/Objectives: Low back pain (LBP) is a widespread public health issue, with myofascial pain syndrome (MPS) being a common cause, affecting 67–100% of patients. However, there are significant challenges in the diagnostic process due to the subjective and unreliable nature of manual palpation. Focused Extracorporeal Shockwave Therapy (F-ESWT), traditionally used for MPS treatment, offers a reproducible and non-invasive mechanical stimulus, making it a potential diagnostic tool. This study evaluated F-ESWT’s diagnostic efficiency in chronic LBP patients by focusing on “recognition” and “referral” of pain. Methods: twenty-eight participants were screened for myofascial trigger points (MTrPs) in the lumbar, gluteal, and thigh regions. Identified MTrPs were stimulated using F-ESWT, and patient feedback was recorded. Results: data showed high diagnostic accuracy for muscles such as the quadratus lumborum, gluteus medius, and gluteus minimus muscles, achieving “referral” rates of 96%, 95%, and 92% and “recognition” rates of 84%, 86%, and 85%, respectively. Other structures like adductors, iliopsoas, erector spinae, and biceps femoris muscle showed consistent but lower diagnostic rates. Conclusions: the study’s findings indicate that F-ESWT effectively reproduces pain patterns, offering a precise, reproducible, and non-invasive diagnostic approach for MPS in chronic LBP. However, they also highlight the necessity for detailed diagnostic criteria in managing myofascial pain.
Background
Although radiation-induced skin injuries are a concern in patients receiving radiation therapy, there are few effective treatments. The aim of this study was to evaluate the protective effects of extracorporeal shock wave therapy (ESWT) on irradiated fibroblasts and mouse skin.
Methods
In the in vitro study of human dermal fibroblasts, the experimental group was subjected to ESWT following irradiation (20 Gy). The control groups were only irradiated or only subjected to ESWT. At 24 or 48 h post-ESWT, cell viability, cell migration, and mRNA and protein expression were measured. In the in vivo study, the experimental group (7 mice) was treated with ESWT following irradiation (45 Gy). The control group (7 mice) was only irradiated. At 8 weeks post-irradiation, dorsal skin was harvested for histopathologic examination and protein isolation.
Results
In dermal fibroblasts, treatment with ESWT increased viability of irradiated cells compared with irradiated-only and untreated cells ( p = 0.005). ESWT increased cell migration 24 h post-irradiation ( p = 0.002), and decreased TGF-β1 protein expression 48 h post-irradiation ( p = 0.024). In mice, ESWT decreased the level of radiation-related skin injury ( p = 0.006). Treatment of irradiated skin with ESWT decreased TGF-β1 ( p = 0.009) and phospho-Smad3 ( p = 0.009) protein expression, as well as decreasing myofibroblasts ( p = 0.047) and increasing vessel density ( p < 0.001).
Conclusions
Our study demonstrated that ESWT alleviated radiation-induced fibrosis by downregulating TGF-β1 expression. It suggests the potential of ESWT for the treatment of radiation-induced fibrosis.
Existing pharmacological treatments for mild neurocognitive disorder (NCD) offer limited effectiveness and adverse side effects. Transcranial pulse stimulation (TPS) utilizing ultrashort ultrasound pulses reaches deep brain regions and may circumvent conductivity issues associated with brain stimulation. This study addresses the gap in TPS research for mild NCD during a critical intervention period before irreversible cognitive degradation. Our objective was to explore the effectiveness and tolerability of TPS in older adults with mild NCD. In an open-label study, 17 older adults (including 10 females and 7 males) with mild NCD underwent TPS for two weeks with three sessions per week. Cognitive evaluations and fMRI scans were conducted pre- and post-intervention. The results indicated changes in functional connectivity in key brain regions, correlating with cognitive improvement at B = 0.087 (CI, 0.007–0.167; p = 0.038). However, cortical thickness measurements showed no significant differences. Here we show that TPS can enhance cognitive function within mild NCD. This proof-of-concept study suggests that TPS has potential as a non-invasive therapy used to attenuate cognitive decline, encouraging further investigation in larger randomized trials. The findings could influence clinical practice by introducing TPS as an adjunctive treatment option and potentially impact policy by promoting its inclusion in new treatment strategies for mild NCD.
Objective
Physiotherapists and physicians continue to seek effective conservative treatments for Achilles tendinopathy. This study aimed to subjectively and objectively determine the therapeutic efficacy of radial shock wave therapy (RSWT) and ultrasound therapy in non-insertional Achilles tendinopathy.
Materials and methods
Thirty-nine patients with non-insertional Achilles tendinopathy were randomly assigned to three experimental groups, i.e., RSWT (group A), ultrasound therapy (group B), and placebo ultrasound (group C) groups. Before the intervention and at weeks 1 and 6 after the treatment, the patients were assessed using the Victorian Institute of Sport Assessment–Achilles (VISA-A) questionnaire and posturographic measurements of step initiation performed on the force platforms under two different conditions (non-perturbed transit and perturbed transit).
Results
Six weeks after therapy, all groups exhibited significantly increased VISA-A scores against the measurement at week 1 after therapy. The post-therapy percentage changes in VISA-A scores were significantly greater in group A compared to group B. The three-way ANOVA demonstrated that treatment type affected sway range in the frontal plane and mean velocity of the centre of foot pressure displacements in the sagittal and frontal planes during quiet standing before step initiation. The Bonferroni post-hoc test showed that the means of all those variables were significantly smaller for group A than for group B patients. The three-way ANOVA revealed an effect of the platform arrangement on transit time and double-support period. The Bonferroni post-hoc test revealed statistically longer transit time for the perturbed vs. non-perturbed trials; a reverse relationship was observed for the double-support period.
Conclusion
The VISA-A showed that RSWT was significantly more effective than sonotherapy for alleviation of pain intensity as well as function and activity improvement in patients with non-insertional Achilles tendinopathy. Therefore, RSWT therapy can be used in clinical practice by physiotherapists to alleviate the symptoms of non-insertional Achilles tendinopathy. Objective data registered by force platforms during quiet standing before and after step initiation did not prove useful for monitoring the progress of treatment applied to patients with non-insertional Achilles tendinopathy between consecutive therapy interventions.
Clinical trial registration:https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000860369, identifier (ACTRN12617000860369).
Aims
To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of
osteochondral defect (OCD), and its effects on the levels of transforming growth factor
(TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone
regeneration.
Methods
The OCD lesion was created on the trochlear groove of left articular cartilage of femur per
rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2,
800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment,
and histopathological analysis, micro-CT scanning, and immunohistochemical staining were
performed for the specimens.
Results
In the histopathological analysis, the macro-morphological grading scale showed a significant
increase, while the histological score and cartilage repair scale of ESWT exhibited a significant
decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up,
ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD.
Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen
and a significant increase in type II collagen within the newly formed hyaline cartilage following
ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β,
BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks.
Conclusion
ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular
matrix proteins and transcription factor involved in the regeneration of articular cartilage
and subchondral bone in an OCD rat model.
This case report describes a novel and unique combination of both electromagnetic and electrohydraulic focused extracorporeal shockwave therapy (ESWT) and extracorporeal magnetotransduction therapy (EMTT) for accelerated healing in a calcaneus epiphyseal fracture with delayed healing in an adolescent Parkour athlete. After a 2.5m jump, the 14-year-old experienced significant heel pain, however avoided telling his parents. After eight weeks, the initial imaging using ultra low dose weight-bearing cone beam CT (WBCT) revealed a calcaneus non-union situation adjacent to the open calcaneal physis. To improve and accelerate bony healing substantially, we chose to apply both combined focused electromagnetic (Storz Ultra, Storz Medical AG, Tägerwillen, CH) and focused electrohydraulic (MTS, Konstanz, Germany) ESWT in a fractioned fashion plus EMTT (Storz Magnetolith, Tägerwillen, CH) in five consecutive weekly sessions while allowing the patient to fully weight bear. The follow-up WBCT after six weeks revealed a near to total healing of the delayed union and being pain-free. Notably, combination therapy with focused ESWT and EMTT did not result in early closure of the calcaneal epiphysis. We conclude that combined focused electromagnetic and electrohydraulic ESWT and EMTT facilitate bony healing in adolescent calcaneal apophyseal fractures without any adverse effects on the open physis. Evidence level IV (case report).
Purpose
The vocal fold tissues undergo nearly continuous and repeated cycles of injury and repair throughout the course of an individual's lifetime. It is well established that certain individuals are at greater risk of lesion development based on personality and behavioral classification. However, these characteristics alone do not wholly predict or explain lesion development or severity. In this review, we discuss current knowledge of mechanotransduction proteins and their potential relevance to tissue homeostasis in the vocal folds.
Method
A review of literature surrounding mechanotransduction and tissue homeostasis as it relates to the vocal folds was conducted. Review of the literature included searches of PubMed, Google Scholar, and other various online peer-reviewed sources. Search terms pertained to mechanosensation, mechanotransduction, mechanically activated channels, mechanical cellular regulation, and other associated concepts and terms. Additional literature was identified through the reference lists of identified papers. Findings of this literature review were then applied to known physiology and pathophysiology of the vocal folds in order to speculate on the contribution of mechanically mediated mechanisms within the vocal fold.
Discussion and Conclusion
Because the vocal folds are such mechanically active structures, withstanding nearly constant external forces, there is strong support for the idea that mechanically sensitive molecular pathways within the vocal fold tissue play a major role in tissue homeostasis in the presence of these considerable forces. As such, mechanotransduction within the vocal fold should be considered and targeted in future biological studies of vocal fold physiology.
Retrospective evaluation of udder recovery following treatment of the inflamed quarter with acoustic pulse technology (APT) of cows with subclinical mastitis was done on 4 Israeli commercial dairy farms. Here, we evaluated the APT treatment as a tool to manage subclinical mastitis and its economic consequences in commercial farms. Recovery of the infected glands following APT treatment was compared to the customary no-treatment (NT) for cows with subclinical mastitis. Over 2 years, 467 cows with subclinical mastitis were identified. Subclinical mastitis was defined by elevated somatic cell count (SCC; >1 × 10⁶ cells/mL) in the monthly test-day milk sample; 222 cows were treated with APT and 245 cows were not treated and served as control. Differences between treatment groups in culling, milk quality, milk yield and bacterial elimination were analyzed. After treatment, cure from bacteria was calculated only for cows with pre-isolated bacteria. The percentage of sampled cows determined as cured (no bacterial finding) in the NT group was 32.7% (35/107) (30.9% Gram negative; 32.4% Gram positive) and in the APT-treated group, 83.9% (42/55) (89.4% Gram negative; 80.6% Gram positive). Culling rate due to mastitis was significantly lower (>90%) in the APT-treated vs. NT group. Recovery was 66.0% in the APT group compared to 11.5% in the NT group at 90 d post-treatment. Average milk volume per cow in the APT-treated group was 16.1% higher compared to NT cows. Based on the study, savings incurred by using APT to treat only subclinical cows per 100-cow herd can total 309 per treated subclinically infected cow.
Background
This is the first study to evaluate the efficacy and safety of transcranial pulse stimulation (TPS) for the treatment of attention-deficit/hyperactivity disorder (ADHD) among young adolescents in Hong Kong.
Methods
This double-blind, randomized, sham-controlled trial included a TPS group and a sham TPS group, encompassing a total of 30 subjects aged 12–17 years who were diagnosed with ADHD. Baseline measurements SNAP-IV, ADHD RS-IV, CGI and executive functions (Stroop tests, Digit Span) and post-TPS evaluation were collected. Both groups were assessed at baseline, immediately after intervention, and at 1-month and 3-month follow-ups. Repeated-measures ANOVAs were used to analyze data.
Results
The TPS group exhibited a 30% reduction in the mean SNAP-IV score at postintervention that was maintained at 1- and 3-month follow-ups.
Conclusion
TPS is an effective and safe adjunct treatment for the clinical management of ADHD.
Clinical trial registration
ClinicalTrials.Gov, identifier NCT05422274.
Skin wounds are a global public health concern, causing around three hundred thousand lives yearly and disabling millions more. More than 95% of these injuries occur in emerging countries where access to health services is limited, and resources are scarce. Variables such as depth, cause, infection, and/or chronicity determine the outcome of skin wounds and whether they hinder the body´s natural healing process. In order to treat deep, chronic and/or complicated skin wounds, various treatments have been developed. Widely used traditional techniques such as asepsis, debridement, and surgery are aimed to prevent further damage and aid scarring but have many disadvantages, including low efficiency results, high healing time rates, and elevated costs. Alternative and novel strategies, such as bioactive dressings and regenerative medicine, are intended to achieve functional and aesthetic tissue recovery while minimizing the rejection risk in other techniques like skin flaps and grafts. The present review outlines the key skin characteristics, a general description of the more common types of wounds and their incidence, and tissue engineered strategies commonly used for skin tissue regeneration.
Objective:
The aim of this study was to investigate the efficacy of low-intensity, high-frequency shock waves in the treatment of temporomandibular joint disorders.
Methods:
Twenty-six patients with temporomandibular joint disorder admitted to the Second Hospital of Shanxi Medical University from August 2022 to December 2022 were selected as study subjects and randomly divided into two groups, A and B, with 13 patients each. In Group A, there were 5 males and 8 females with an average age of 38.85 ± 11.03 years. In Group B, there were 4 males and 9 females with an average age of 39.15 ± 11.16 years. Group A was the control group, which received routine treatment (manual massage + transcutaneous electrical nerve stimulation + ultrashort wave therapy) plus sham shock wave therapy; Group B was the experimental group, which received routine treatment (manual massage + transcutaneous electrical nerve stimulation + ultrashort wave therapy) plus shock wave therapy. The routine treatment was administered once/day, five times per week for a total of 2 weeks of treatment. In addition, shock wave therapy was administered once every 5 days, and the treatment was administered three times. The treatment period was 2 weeks, and the two groups were compared before treatment, at the end of the treatment period, and 4 weeks after treatment. The pain level of the two groups was assessed by the visual analogue scale (VAS) before and after treatment, and the temporomandibular opening index (TOI) before and after treatment was compared between the two groups. VAS and TOI scores were evaluated using the Mann-Whitney U-test, the Kruskal-Wallis H-test and two-way ANOVA.
Results:
There was no significant difference in the VAS score and temporomandibular opening index between the two groups before treatment (p = .829 and .75, respectively). After 2 weeks of treatment, the VAS score and temporomandibular joint opening index of both groups were significantly improved compared to those before therapy. In addition, the VAS score and temporomandibular joint opening index in the experimental group were significantly better than those in the control group (p < .001 and <.001, respectively). There was a small increase in scores 4 weeks after the treatment compared to just after the treatment period, but the difference was not significant.
Conclusion:
This is a preliminary small sample study that demonstrates the positive effect of using low-intensity, high-frequency shock waves on the treatment of temporomandibular joint disorders and is worthy of clinical promotion.
Hypertrophic scars and keloids can be aesthetically unpleasant and may be associated with functional and psychosocial impairment. Treating a pathological scar, once established, can be difficult and frustrating. For this reason, prevention of excessive scarring is preferable and much more efficient than treatment, both in case of elective surgery and accidental injury. Prevention measures to reduce scar formation should be applied even before starting any surgical procedure: the surgeon must carefully design a plan to avoid skin stretching tension on the wound edges and prevent factors that promote excessive inflammation such as infection, foreign bodies, or delayed healing. Postoperatively, many invasive and noninvasive options to prevent excessive scar formation are available, nevertheless, there is no single therapy proven to have a consistent and absolute efficacy. A personalized and multimodal approach is recommended and may include the use of physical therapy, silicone sheeting or topical silicone gel, pressure garments, and steroid injections. Patient history of scarring, etiology of the injury, patient expectations, and the likelihood of compliance, influence in the selection of a preventive therapy.
Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment for chronic tendinopathies, however little is known about the in-vivo biological mechanisms of ESWT. Using microdialysis, we examined the real-time biological response of healthy and pathological tendons to ESWT. A single session of ESWT was administered to the mid-portion of the Achilles tendon in thirteen healthy individuals (aged 25.7 ± 7.0 years) and patellar or Achilles tendon of six patients with tendinopathies (aged 39.0 ± 14.9 years). Dialysate samples from the surrounding peri-tendon were collected before and immediately after ESWT. Interleukins (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, vascular endothelial growth factor and interferon-γ were quantified using a cytometric bead array while gelatinase activity (MMP-2 and -9) was examined using zymography. There were no statistical differences between the biological tissue response to ESWT in healthy and pathological tendons. IL-1β, IL-2, IL-6 and IL-8 were the cytokines predominantly detected in the tendon dialysate. IL-1β and IL-2 did not change significantly with ESWT. IL-6 and IL-8 concentrations were elevated immediately after ESWT and remained significantly elevated for four hours post-ESWT (p < 0.001). Pro-forms of MMP-2 and -9 also increased after ESWT (p < 0.003), whereas there were no significant changes in active MMP forms. In addition, the biological response to ESWT treatment could be differentiated between possible responders and non-responders based on a minimum 5-fold increase in any inflammatory marker or MMP from pre- to post-ESWT. Our findings provide novel evidence of the biological mechanisms underpinning ESWT in humans in vivo. They suggest that the mechanical stimulus provided by ESWT might aid tendon remodelling in tendinopathy by promoting the inflammatory and catabolic processes that are associated with removing damaged matrix constituents. The non-response of some individuals may help to explain why ESWT does not improve symptoms in all patients and provides a potential focus for future research.
Capsular fibrosis is the most frequent long-term complication after insertion of silicone devices. Today, mainly direct immunostimulation and subclinical infection are held responsible for inducing and maintaining inflammatory reactions, which lead to overwhelming extracellular matrix formation. Extracorporeal shock waves (ESWs) are capable of inhibiting inflammatory processes and revealing antibacterial capacity. In our previous study, we observed decelerated capsule development after application of a single shock wave immediately after surgery. The purpose of this study was to evaluate the effects of multiple ESWT after insertion of silicone implants in the same rodent model. Therefore, silicone prostheses were inserted into a submuscular pocket in 12 additional male Lewis rats, and shock waves were administered over a 14-d interval. At 35 d (n = 6) and 100 d (n = 6) after insertion, silicone implants and surrounding capsule tissue were removed and prepared for histologic and immunohistochemical analysis, as well as polymerase chain reaction (Ccl2, CD68, transforming growth factor β1, matrix metalloproteinase 2). Compared with the control group, multiple ESWT had no effect on day 35, but resulted in a significantly thinner capsule on day 100 (825.8 ± 313.2 vs. 813.3 ± 47.9, p = 0.759, and 1062.3 ± 151.9 vs. 495.4 ± 220.4, p < 0.001, respectively). The capsule was even thinner than after a single shock wave application, which had been found to result in thinner capsules at every time point in our previous study. This active degradation of the fibrous envelope caused by multiple ESWs was accompanied by synergistic alterations in pro- and anti-fibrotic proteins (transforming growth factor β1 and matrix metalloproteinase 2, respectively). In conclusion, after insertion of silicone devices, single ESWT is capable of decelerating capsule formation in contrast to multiple ESWT, which degrades fibrotic tissue. These findings seem to be associated with inhibition of inflammation and beneficial effects on pro- and anti-fibrotic proteins.
Tissue-engineered xenografts represent a promising treatment option in heart valve disease. However, inflammatory response leading to graft failure and incomplete in vitro repopulation with recipient cells remain challenging. Shock waves (SWs) were shown to modulate inflammation and to enhance re-epithelialization. We therefore aimed to investigate whether SWs could serve as a feasible adjunct to tissue engineering.
Porcine aortic pieces were decellularized using sodium deoxycholate and sodium dodecylsulphate and implanted subcutaneously into C57BL/6 mice (n = 6 per group). The treatment (shock wave therapy, SWT) group received SWs (0.1 mJ/mm(2), 500 impulses, 5 Hz) for modulation of inflammatory response directly after implantation; control animals remained untreated (CTR). Grafts were harvested 72 h and 3 weeks after implantation and analysed for inflammatory cytokines, macrophage infiltration and polarization, osteoclastic activity and calcification. Transmission electron microscopy (TEM) was performed. Endothelial cells (ECs) were treated with SWs and analysed for macrophage regulatory cytokines. In an ex vivo experimental set-up, decellularized porcine aortic valve conduits were reseeded with ECs with and without SWT (0.1 mJ/mm(2), 300 impulses, 3 Hz), fibroblasts as well as peripheral blood mononuclear cells (all human) and tested in a pulsatile flow perfusion system for cell coverage.
Treated ECs showed an increase of macrophage migration inhibitory factor and macrophage inflammatory protein 1β, whereas CD40 ligand and complement component C5/C5a were decreased. Subcutaneously implanted grafts showed increased mRNA levels of tumour necrosis factor α and interleukin 6 in the treatment group. Enhanced repopulation with recipient cells could be observed after SWT. Augmented macrophage infiltration and increased polarization towards M2 macrophages was observed in treated animals. Enhanced recruitment of osteoclastic cells in proximity to calcified tissue was found after SWT. Consequently, SWT resulted in decreased areas of calcification in treated animals. The reseeding experiment revealed that fibroblasts showed the best coverage compared with other cell types. Moreover, SW-treated ECs exhibited enhanced repopulation compared with untreated controls.
SWs reduce the calcification of subcutaneously implanted decellularized xenografts via the modulation of the acute macrophage-mediated inflammatory response and improves the in vitro repopulation of decellularized grafts. It may therefore serve as a feasible adjunct to heart valve tissue engineering.
© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
[Purpose] The purpose of this meta-analysis was to assess the effects of extracorporeal shock wave therapy (ESWT) on reducing spasticity immediately and 4 weeks after application of ESWT. [Subjects and Methods] We searched PubMed, TCL, Embase, and Scopus from their inception dates through June 2013. The key words "muscle hypertonia OR spasticity" were used for spasticity, and the key words "shock wave OR ESWT" were used for ESWT. Five studies were ultimately included in the meta-analysis. [Results] The Modified Ashworth Scale (MAS) grade was significantly improved immediately after ESWT compared with the baseline values (standardized mean difference [SMD], -0.792; 95% confidence interval [CI], -1.001 to -0.583). The MAS grade at four weeks after ESWT was also significantly improved compared with the baseline values (SMD, -0.735; 95% CI, -0.951 to -0.519). [Conclusion] ESWT has a significant effect on improving spasticity. Further standardization of treatment protocols including treatment intervals and intensities needs to be established and long-term follow up studies are needed.
Object:
Extracorporeal shock wave therapy (ESWT) is widely used for the clinical treatment of various human diseases. Recent studies have demonstrated that low-energy ESWT upregulates the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis and functional recovery in myocardial infarction and peripheral artery disease. Many previous reports suggested that VEGF produces a neuroprotective effect to reduce secondary neural tissue damage after spinal cord injury (SCI). The purpose of the present study was to investigate whether low-energy ESWT promotes VEGF expression and neuroprotection and improves locomotor recovery after SCI.
Methods:
Sixty adult female Sprague-Dawley rats were randomly divided into 4 groups: sham group (laminectomy only), sham-SW group (low-energy ESWT applied after laminectomy), SCI group (SCI only), and SCI-SW group (low-energy ESWT applied after SCI). Thoracic spinal cord contusion injury was inflicted using an impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) Scale (open field locomotor score) at different time points over 42 days after SCI. Hematoxylin and eosin staining was performed to assess neural tissue damage in the spinal cord. Neuronal loss was investigated by immunostaining for NeuN. The mRNA expressions of VEGF and its receptor, Flt-1, in the spinal cord were assessed using real-time polymerase chain reaction. Immunostaining for VEGF was performed to evaluate VEGF protein expression in the spinal cord.
Results:
In both the sham and sham-SW groups, no animals showed locomotor impairment on BBB scoring. Histological analysis of H & E and NeuN stainings in the sham-SW group confirmed that no neural tissue damage was induced by the low-energy ESWT. Importantly, animals in the SCI-SW group demonstrated significantly better locomotor improvement than those in the SCI group at 7, 35, and 42 days after injury (p < 0.05). The number of NeuN-positive cells in the SCI-SW group was significantly higher than that in the SCI group at 42 days after injury (p < 0.05). In addition, mRNA expressions of VEGF and Flt-1 were significantly increased in the SCI-SW group compared with the SCI group at 7 days after injury (p < 0.05). The expression of VEGF protein in the SCI-SW group was significantly higher than that in the SCI group at 7 days (p < 0.01).
Conclusions:
The present study showed that low-energy ESWT significantly increased expressions of VEGF and Flt-1 in the spinal cord without any detrimental effect. Furthermore, it significantly reduced neuronal loss in damaged neural tissue and improved locomotor function after SCI. These results suggested that low-energy ESWT enhances the neuroprotective effect of VEGF in reducing secondary injury and leads to better locomotor recovery following SCI. This study provides the first evidence that low-energy ESWT can be a safe and promising therapeutic strategy for SCI.
Shockwave treatment accelerates impaired wound healing in diverse clinical situations. However, the mechanisms underlying the beneficial effects of shockwaves have not yet been fully revealed. Since cell proliferation is a major requirement in the wound healing cascade, we used in vitro studies and an in vivo wound healing model to study whether shockwave treatment influences proliferation by altering major extracellular factors and signaling pathways involved in cell proliferation. We identified extracellular ATP, released in an energy- and pulse number-dependent manner, as a trigger of the biological effects of shockwave treatment. Shockwave treatment induced ATP release, increased Erk1/2 and p38 MAPK activation, and enhanced proliferation in three different cell types (C3H10T1/2 murine mesenchymal progenitor cells, primary human adipose derived stem cells, human Jurkat T cell line) in vitro. Purinergic signaling-induced Erk1/2 activation was found to be essential for this proliferative effect, which was further confirmed by in vivo studies in a rat wound healing model where shockwave treatment induced proliferation and increased wound healing in an Erk1/2 dependent fashion. In summary, this report demonstrates that shockwave treatment triggers release of cellular ATP, which subsequently activates purinergic receptors and finally enhances proliferation in vitro and in vivo via downstream Erk1/2 signaling. In conclusion, our findings shed further light on the molecular mechanisms by which shockwave treatment exerts its beneficial effects. These findings could help to improve the clinical use of shockwave treatment for wound healing.
Objectives
Low energy shock waves have been shown to induce angiogenesis, improve left ventricular ejection fraction and decrease angina symptoms in patients suffering from chronic ischemic heart disease. Whether there is as well an effect in acute ischemia was not yet investigated.
Methods
Hind-limb ischemia was induced in 10–12 weeks old male C57/Bl6 wild-type mice by excision of the left femoral artery. Animals were randomly divided in a treatment group (SWT, 300 shock waves at 0.1 mJ/mm2, 5 Hz) and untreated controls (CTR), n = 10 per group. The treatment group received shock wave therapy immediately after surgery.
Results
Higher gene expression and protein levels of angiogenic factors VEGF-A and PlGF, as well as their receptors Flt-1 and KDR have been found. This resulted in significantly more vessels per high-power field in SWT compared to controls. Improvement of blood perfusion in treatment animals was confirmed by laser Doppler perfusion imaging. Receptor tyrosine kinase profiler revealed significant phosphorylation of VEGF receptor 2 as an underlying mechanism of action. The effect of VEGF signaling was abolished upon incubation with a VEGFR2 inhibitor indicating that the effect is indeed VEGFR 2 dependent.
Conclusions
Low energy shock wave treatment induces angiogenesis in acute ischemia via VEGF receptor 2 stimulation and shows the same promising effects as known from chronic myocardial ischemia. It may therefore develop as an adjunct to the treatment armentarium of acute muscle ischemia in limbs and myocardium.
It has been shown that focal adhesion proteins are crucial for the ability of cells to transmit external forces and to generate cytoskeletal tension. Force transmission over considerable distances and stress focusing at the focal adhesion sites make them prime candidates for mechanosensors. Temporal and spatial changes in the cytoskeletal protein configuration due to mechanical stimulation have been detected and characterized by a wide range of biophysical techniques, including magnetic twisting, magnetic tweezer, traction microscopy, atomic force microscopy, nanoscale particle tracking, and many more. The combination of these techniques will help to understand force transmission and structural remodeling in cells under loading conditions. Force transmission and force sensing represent basic biological processes that are crucial for a variety of higher fundamental cell functions including cell division, motility, and differentiation that have implications in medicine and biology.
Objective:
Can stimulation of nerve growth factors by focused transcranial extracorporeal shock wave therapy (TESWT) be made effective for persons within unresponsive wakefulness syndrome (apallic syndrome)?
Design:
Between eight and 18 years after the brain lesion, five patients with unresponsive wakefulness syndrome of differing severity received TESWT with the device Duolith (Storz Medical) during four-week physicomedical complex therapies. In the previous years they had been treated with the same complex therapies without TESWT. The vigilance did not change.
Results:
After two-four years and an average of 5.2 treatment series, the patients' abilities improved by 135.9% on the German Coma Remission Scale (KRS) and by 43.6% on the Glasgow Coma Scale. In the motor area of the KRS, the patients improved by 64.3%. Three PEG feeding tubes could be removed, nonverbal communication initiated four times.
Conclusion:
In this longitudinal observation study, focused TESWT stimulated vigilance in patients with unresponsive wakefulness syndrome. The precise neurophysiological effects remain to be verified by a study of the clinical results.
Penile extracorporeal low-intensity shock wave therapy (LIST) to the penis has recently emerged as a novel and promising modality in the treatment of erectile dysfunction (ED). LIST has angiogenic properties and stimulates neovascularization. If applied to the corpora cavernosa, LIST can improve penile blood flow and endothelial function. In a series of clinical trials, including randomized double-blind sham-controlled studies, LIST has been shown to have a substantial effect on penile hemodynamics and erectile function in patients with vasculogenic ED. LIST is effective in patients who are responsive to phosphodiesterase 5 inhibitors (PDE5i) and can also convert PDE5i nonresponders to responders. The response to LIST wanes gradually over time, and after 2 years, about half of the patients maintain their function. Extensive research is needed to understand the effect of LIST on erectile tissue, to modify the treatment protocol to maximize its outcomes, and to identify the patients who will benefit the most from this treatment.
There is no gold standard for treatment of bone marrow edema syndrome of the hip (BMESH). Usually, treatment is conservative, owing to the favorable and self-limiting prognosis. In musculoskeletal disorders, the effectiveness of extracorporeal shock wave therapy (ESWT) has been widely recognized and recent research supports its use in the treatment of the first stages of avascular osteonecrosis of the proximal femur and in other conditions where bone marrow edema is present. On this basis, we performed a prospective study to evaluate the effectiveness of ESWT in normalizing the symptoms and imaging features of BMESH. Twenty consecutive symptomatic patients underwent two treatments of high-energy ESWT and were followed-up at 2, 3 and 6 months, with a final clinical follow-up at mean 15.52 ± 1.91 months. Patients underwent magnetic resonance imaging of the hip and were evaluated according to the Harris hip score. The mean improvement in HHS over the course of the study was of 58.5 ± 14.9 points (p < 0.0001), and the mean edema area reduced from 981.9 ± 453.2 mm(2) pre-treatment to 107.8 ± 248.1 mm(2) at 6 months. ESWT seems to be a powerful, non-pharmacological tool that produces rapid pain relief and functional improvement and aids the normalization of the vascular and metabolic impairments which characterize BMESH.
Cells have the capacity to convert mechanical stimuli into chemical changes. This process is based on the tensegrity principle, a mechanism of tensional integrity. To date, this principle has been demonstrated to act in physiological processes such as mechanotransduction and mechanosensing at different scales (from cell sensing through integrins to molecular mechanical interventions or even localized massage). The process involves intra- and extracellular components, including the participation of extracellular matrix (ECM) and microtubules that act as compression structures, and actin filaments which act as tension structures. The nucleus itself has its own tensegrity system which is implicated in cell proliferation, differentiation, and apoptosis. Despite present advances, only the tip of the iceberg has so far been uncovered regarding the role of ECM compounds in influencing biotensegrity in pathological processes. Groups of cells, together with the surrounding ground substance, are subject to different and specific forces that certainly influence biological processes. In this paper, we review the current knowledge on the role of ECM elements in determining biotensegrity in malignant processes and describe their implication in therapeutic response, resistance to chemo- and radiotherapy, and subsequent tumor progression. Original data based on the study of neuroblastic tumors will be provided.
Regenerative therapy is one of the most challenging and intriguing branches of modern medicine. Basic research has demonstrated the effectiveness of extracorporeal shockwaves (ESWT) in stimulating biological activities that involve intra-cell and cell-matrix interactions. These interactions are at the basis of the current clinical applications, and open the horizons to new applications in tissue regeneration. It is also feasible that shock waves could be used to treat various orthopaedic pathologies, removing the need for surgery. However, suitable translational studies need to be performed before ESWT can become a valid alternative to surgery. © 2013 S. Karger AG, Basel.
Low-energy extracorporeal shock wave treatment (ESWT) is a relatively new therapeutic tool that is widely used for the treatment of epicondylitis and plantar fasciitis and to foster bone and wound healing. Shock waves, sonic pulses with high energy impact, are thought to induce biochemical changes within the targeted tissues through mechanotransduction. The biological effects of ESWT are manifested in improved vascularization, the local release of growth factors, and local anti-inflammatory effects, but the target cells too are influenced. ESWT appears to have differential effects on peripheral nerves and has been proved to promote axonal regeneration after axotomy. This review discusses the effects of ESWT on intact and injured peripheral nerves and suggests a multiple mechanism of action.
There is currently great interest in the use of Extracorporeal Shock Wave Therapy (ESWT) and in clarifying the mechanisms of action in tendon pathologies. The success rate ranges from 60% to 80% in epicondylitis, plantar fasciitis, cuff tendinitis, trocanteritis, Achilles tendinitis or jumper's knee. In contrast to urological treatments (lithotripsy), where shockwaves are used to disintegrate renal stones, in musculoskeletal treatments (orthotripsy), shockwaves are not being used to disintegrate tissues, but rather to microscopically cause interstitial and extracellular biological responses and tissue regeneration. The researchers are interesting to investigate the biological effects which support the clinical successes. Some authors speculated that shockwaves relieve pain in insertional tendinopathy by hyper-stimulation analgesia. Many recent studies demonstrated the modulations of shockwave treatment including neovascularization, differentiation of mesenchymal stem cells and local release of angiogenetic factors. The experimental findings confirm that ESWT decrease the expression of high levels of inflammatory mediators (matrix metalloproteinases and inter-leukins). Therefore, ESWT produces a regenerative and tissue-repairing effect in musculoskeletal tissues, not merely a mechanical disintegrative effect as generally before assumed. Based on the encouraging results of clinical and experimental studies, the potential of ESWT appears to be emerging. The promising outcome after this non-invasive treatment option in tendinitis care justifies the indication of shockwave therapy. Further studies have to be performed in order or determine optimum treatment parameters and will bring about an improvement in accordance with evidence-based medicine. Finally, meta-analysis studies are necessary to demonstrate the efficacy and safety of ESWT in treating tendinopathies.
In vitro models of human tenocytes derived from healthy as well as from ruptured tendons were established, characterized and used at very early passage (P1) to evaluate the effects of Extracorporeal Shock Wave Treatment (ESWT). The molecular analysis of traditional tenocytic markers, including Scleraxis (Scx), Tenomodulin (Tnm), Tenascin-C (Tn-C) and Type I and III Collagens (Col I and Col III), permitted us to detect in our samples the simultaneous expression of all these genes and allowed us to compare their levels of expression in relationship to the source of the cells and treatments. In untreated conditions, higher molecular levels of Scx and Col I in tenocytes from pathological compared to healthy samples have been detected, suggesting - in the cells from injured tendon - the natural trigger of an early differentiation and repairing program, which depends by Scx and requires an increase in collagen expression. When ESWT (at the dose of 0.14 mJ/mm(2)) was applied to cultured tenocytes explanted from injured source, Scx and Col I were significantly diminished compared to healthy counterpart, indicating that such natural trigger maybe delayed by the treatment, in order to promote cellular repair. Herein, we show for the first time that ESWT enhances in vitro functional activities of ruptured tendon-derived tenocytes, such as proliferation and migration, which could probably contributes to tendon healing in vivo.
The biologic action of extracorporeal shock wave application on the musculoskeletal system is understood poorly. To prove the hypothesis that alterations of tissue concentrations of substance P and prostaglandin E2 are involved in the biologic action of shock waves, extracorporeal shock waves with energy flux density of 0.9 mJ/mm2 (1500 pulses at 1/s) were applied in vivo to the distal femur of rabbits. The concentrations of substance P and prostaglandin E2 eluated from the periosteum of the femur were measured. Compared with the untreated contralateral hindlimbs, substance P release from the periosteum from the femur was increased 6 and 24 h after extracorporeal shock wave application, but was decreased 6 weeks after extracorporeal shock wave application. By contrast, extracorporeal shock wave application did not result in altered prostaglandin E2 release from the periosteum from the femur. Remarkably, there was a close relationship between the time course of substance P release found here, and the well-known clinical time course of initial pain occurence and subsequent pain relief after extracorporeal shock wave application to tendon diseases. Accordingly, substance P might be involved in the biologic action of extracorporeal shock wave application on tissue of the musculoskeletal system. This is the first study providing insights into the molecular mechanisms of extracorporeal shock wave application to the musculoskeletal system.
Background: The effects of extracorporeal shock wave (ESW) on adhesion and migration of osteoblasts have not been reported until now.
Results: Optimal intensity shock wave promotes osteoblast adhesion and migration.
Conclusion: ESW promotes the adhesion and migration of osteoblasts via integrin β1-mediated expression of phosphorylated FAK.
Significance: This provides a mechanistic basis for improving the effectiveness of ESW treatment in fracture healing and tissue engineering.
Mechanotransduction is the physiological process where cells sense and respond to mechanical loads. This paper reclaims the term “mechanotherapy” and presents the current scientific knowledge underpinning how load may be used therapeutically to stimulate tissue repair and remodelling in tendon, muscle, cartilage and bone.
The purpose of this short article is to answer a frequently asked question “How precisely does exercise promote tissue healing?” This is a fundamental question for clinicians who prescribe exercise for tendinopathies, muscle tears, non-inflammatory arthropathies and even controlled loading after fractures. High-quality randomised controlled trials and systematic reviews show that various forms of exercise or movement prescription benefit patients with a wide range of musculoskeletal problems.1–4 But what happens at the tissue level to promote repair and remodelling of tendon, muscle, articular cartilage and bone?
The one-word answer is “mechanotransduction”, but rather than finishing there and limiting this paper to 95 words, we provide a short illustrated introduction to this remarkable, ubiquitous, non-neural, physiological process. We also re-introduce the term “mechanotherapy” to distinguish therapeutics (exercise prescription specifically to treat injuries) from the homeostatic role of mechanotransduction. Strictly speaking, mechanotransduction maintains normal musculoskeletal structures in the absence of injury. After first outlining the process of mechanotransduction, we provide well-known clinical therapeutic examples of mechanotherapy–turning movement into tissue healing.
The cambium cells of the periosteum, which are known osteoprogenitor cells, have limited suitability for clinical applications of tissue engineering in their native state due to their low cell number (2-5 cells thick). Extracorporeal shock waves (ESWs) have been shown to cause rapid periosteal cambium cell proliferation and subsequent periosteal osteogenesis. This work investigates a novel strategy for orthotopic bone generation: applying ESW therapy as a noninvasive, inexpensive, and rapid method for stimulating cambium cell proliferation, and combining these cells with a bioactive scaffold for bone growth. ESWs applied to the rabbit medial tibia resulted in a significant 2.7-fold increase in cambium cell number and a 4-fold increase in cambium cell thickness at 4 days post-ESW. ESW-stimulated, or nontreated control, periosteal cells were elevated in situ and overlaid on an anorganic bovine bone scaffold to interrogate their ability to form bone. At 2 weeks post-surgery, there was a significant increase in all key outcome variables for the ESW-stimulated group when compared with controls: a 4-fold increase in osseous tissue in the upper half of the scaffold underlying the periosteum; a 12-fold increase in osseous tissue overlying the scaffold; and a 2-fold increase in callus size. These results successfully demonstrated the efficacy of ESW-stimulated periosteum for orthotopic bone generation.
The exact nature of shock wave (SW) action is not, as yet, fully understood, although a possible hypothesis may be that shock waves induce neoangiogenesis. To test this hypothesis, a three-dimensional (3D) culture model on Matrigel was developed employing a human microvascular endothelial cell line (HMEC-1) which was stimulated with low energy soft- focused SW generated by an SW lithotripter. After 12 hours we observed a statistically significant increase in capillary connections subsequent to shock-wave treatment in respect to the control group and a marked 3-hour down-regulation in genes involved in the apoptotic processes (BAX, BCL2LI, GADD45A, PRKCA), in cell cycle (CDKN2C, CEBPB, HK2, IRF1, PRKCA), oncogenes (JUN, WNT1), cell adhesion (ICAM-1), and proteolytic systems (CTSD, KLK2, MMP10). Our preliminary results indicate that microvascular endothelial cells in vitro quickly respond to SW, proliferating and forming vessel-like structures, depending on the energy level employed and the number of shocks released. The early decreased expression in the analysed genes could be interpreted as the first reactive response of the endothelial cells to the external stimuli and the prelude to the events characterizing the neo-angiogenic sequence.
It is known that free nerve endings are degenerated after application of shock waves. We therefore hypothesized that the application of shock waves to muscle induces dysfunction of neuromuscular transmission at neuromuscular junctions. We investigated changes in neuromuscular transmission in response to shock wave application. Sprague-Dawley rats were used in this study. Two thousand shock waves at an energy flux density of 0.18 mJ/mm(2) were applied to their right calf muscles. Neuromuscular junctions of gastrocnemius muscles were evaluated using rhodamine-α-bungarotoxin on the day of treatment (n = 5). Amplitude and latency of compound muscle action potentials were measured on the day of treatment and 1, 2, 4, 6, and 8 weeks after treatment (n = 10, each group). Degenerated acetylcholine receptors existed in all treated muscles. Although the action potential amplitude on the treated side was significantly less than on the control side from the day of treatment (25.1 ± 7.8 vs. 34.5 ± 9.1, p = 0.012) to 6 weeks (27.9 ± 7.2 vs. 34.5 ± 7.2, p = 0.037), there was no significant difference at 8 weeks. There was no significant difference in transmission latency between the groups. The application of shock waves to muscle induced a transient dysfunction of nerve conduction at neuromuscular junctions.
The sources of shockwave generation include electrohydraulic, electromagnetic and piezoelectric principles. Electrohydraulic shockwaves are high-energy acoustic waves generated under water explosion with high voltage electrode. Shockwave in urology (lithotripsy) is primarily used to disintegrate urolithiasis, whereas shockwave in orthopedics (orthotripsy) is not used to disintegrate tissues, rather to induce tissue repair and regeneration. The application of extracorporeal shockwave therapy (ESWT) in musculoskeletal disorders has been around for more than a decade and is primarily used in the treatment of sports related over-use tendinopathies such as proximal plantar fasciitis of the heel, lateral epicondylitis of the elbow, calcific or non-calcific tendonitis of the shoulder and patellar tendinopathy etc. The success rate ranged from 65% to 91%, and the complications were low and negligible. ESWT is also utilized in the treatment of non-union of long bone fracture, avascular necrosis of femoral head, chronic diabetic and non-diabetic ulcers and ischemic heart disease. The vast majority of the published papers showed positive and beneficial effects. FDA (USA) first approved ESWT for the treatment of proximal plantar fasciitis in 2000 and lateral epicondylitis in 2002. ESWT is a novel non-invasive therapeutic modality without surgery or surgical risks, and the clinical application of ESWT steadily increases over the years. This article reviews the current status of ESWT in musculoskeletal disorders.
Background:
Little has been reported about the biologic effect of shock waves on human normal or pathologic tendon tissue. We hypothesized that inflammatory cytokine and MMP production would be down-regulated by shock wave stimulation.
Materials and methods:
Diseased Achilles tendon tissue and healthy flexor hallucis longus tissue were used. Shock wave treatment was applied to cultured cells at 0.17 mJ/mm(2)energy 250, 500, 1000, and 2000 times.
Results:
A dose-dependent decrease in cell viability was noted in cells receiving 1000 and 2000 shocks (86.0 +/- 5.6%, p = 0.01 and 72.4 +/- 8.9%, p = 0.001) as compared with the normal control. Cell count in the 500-shock group increased by 23.4% as compared with the control (p = 0.05). The concentration of MMP 1, 2, and 13 was higher in diseased tenocytes as compared with normal cells (p = 0.04, all comparisons). IL-6 levels were higher in the diseased tenocytes as compared with normal tenocytes (44.10 +/- 16.72 versus 0.21 +/- 0.55 ng/ml, (p < 0.05). IL-1 levels in normal cells increased (2.24 +/- 5.02 ng/ml to 9.31 +/- 6.85 ng/ml) after shock wave treatment (p = 0.04). In diseased tenocytes, levels of MMP-1 (1.12 +/- 0.23 to 0.75 +/- 0.24 ng/ml; p = 0.04) and MMP-13 (1.43 +/- 0.11 to 0.80 +/- 0.15 ng/ml; p = 0.04) were significantly decreased after shock wave treatment. The IL-6 level in diseased tenocytes was decreased (44.10 +/- 16.72 to 14.66 +/- 9.49 ng/ml) after shock wave treatment (p = 0.04).
Conclusion:
Higher levels of MMPs and ILs were found in human tendinopathy-affected tenocytes as compared with normal cells. ESWT decreased the expression of several MMPs and ILs.
Clinical relevance:
This mechanism may play an important role in shock wave treatment of tendinopathy clinically.
Macrophages are widely distributed immune system cells that play an indispensable role in homeostasis and defense. They can be phenotypically polarized by the microenvironment to mount specific functional programs. Polarized macrophages can be broadly classified in two main groups: classically activated macrophages (or M1), whose prototypical activating stimuli are IFNgamma and LPS, and alternatively activated macrophages (or M2), further subdivided in M2a (after exposure to IL-4 or IL-13), M2b (immune complexes in combination with IL-1beta or LPS) and M2c (IL-10, TGFbeta or glucocorticoids). M1 exhibit potent microbicidal properties and promote strong IL-12-mediated Th1 responses, whilst M2 support Th2-associated effector functions. Beyond infection M2 polarized macrophages play a role in resolution of inflammation through high endocytic clearance capacities and trophic factor synthesis, accompanied by reduced pro-inflammatory cytokine secretion. Similar functions are also exerted by tumor-associated macrophages (TAM), which also display an alternative-like activation phenotype and play a detrimental pro-tumoral role. Here we review the main functions of polarized macrophages and discuss the perspectives of this field.
Extracorporeal shock wave therapy (ESWT) is broadly used as a non-surgical therapy in various diseases for its pro-angiogenic and anti-inflammatory effects. However, the molecular mechanisms translating tissue exposure to shock waves (SW) in a biological response with potential therapeutic activity are largely unknown. As macrophages take part in both the onset and amplification of the inflammatory response, and well in its resolution, we investigated the effect of SW on their biology.
Human monocyte-derived macrophages were polarized to classic (M1) pro-inflammatory macrophages or alternative (M2) anti-inflammatory macrophages and exposed to SW ad different intensities. Expression levels of marker genes of macrophage activation were measured by qPCR at different time points.
SW did not induce activation of resting macrophages at any energy level used. Conversely, when used at low energy SW caused a significant inhibition of some M1 marker genes (CD80, COX2, CCL5) in M1 macrophages and a significant synergistic effect for some M2 marker genes (ALOX15, MRC1, CCL18) in M2 macrophages. SW also affected cytokine and chemokine production, inducing in particular a significant increase in IL-10 and reduction in IL-1β production.
Macrophage exposure to low energy SW dampens the induction of the pro-inflammatory profile characterizing M1 macrophages and promotes the acquisition of an anti-inflammatory profile synergizing with macrophage alternative activation.
Copyright © 2015. Published by Elsevier Ltd.
Cells actively sense and process mechanical information that is provided by the extracellular environment to make decisions about growth, motility and differentiation. It is important to understand the underlying mechanisms given that deregulation of the mechanical properties of the extracellular matrix (ECM) is implicated in various diseases, such as cancer and fibrosis. Moreover, matrix mechanics can be exploited to program stem cell differentiation for organ-on-chip and regenerative medicine applications. Mechanobiology is an emerging multidisciplinary field that encompasses cell and developmental biology, bioengineering and biophysics. Here we provide an introductory overview of the key players important to cellular mechanobiology, taking a biophysical perspective and focusing on a comparison between flat versus three dimensional substrates.
Copyright © 2015. Published by Elsevier B.V.
To evaluate the efficacy, safety and patient satisfaction rate with low-intensity extracorporeal shockwave therapy (LiESWT) in Australian men with erectile dysfunction (ED), as LiESWT induces neovascularisation and potentially enhances penile perfusion and improves erectile function.
Open-label single-arm prospective study of patients with ED with five-item version of the International Index of Erectile Function (IIEF-5) scores of >12 at baseline were enrolled after informed consent. Patient demographics, change in IIEF-5 and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores, and overall satisfaction score (on a 5-point scale) were recorded. Treatment consists of 3000 shockwaves (1000 shockwaves to the distal penis, base of penis and corporal bodies at the perineum) twice weekly for 6 weeks.
All patients had tried and failed oral phosphodiesterase type 5 inhibitors and most of the patients hah had ED for >18 months [mean (range) 21.8 (6-60) months]. No side-effects to LiESWT were reported. Most patients reported an improvement in IIEF-5 score by 5 points (60%) and EDITS Index score by >50% (70%). Most patients were satisfied (scoring 4 out of 5; 67%) and would recommend the therapy to their friends (80%).
LiESWT appears to improve erectile function, is safe and potential plays an important role in penile rehabilitation in men whom failed medical therapy.
© 2015 The Authors. BJU International © 2015 BJU International.
Endothelial progenitor cells (EPCs) are adult stem cells that play a central role in neovascularization. EPCs are mobilized from bone marrow into peripheral blood, attach to existing endothelial cells, and then transmigrate across the endothelium into tissues, where they proliferate,
differentiate, and form new blood vessels. In the process, EPCs are exposed to shear stress, a biomechanical force generated by flowing blood and tissue fluid flow. When cultured EPCs are exposed to controlled levels of shear stress in a flow-loading device, their bioactivities in terms of
proliferation, anti-apoptosis, migration, production of bioactive substances, anti-thrombosis, and tube formation increase markedly. Expression of endothelial marker genes and proteins by EPCs also increases in response to shear stress, and they differentiate into mature endothelial cells.
Great advances have been made in elucidating the mechanisms by which mature endothelial cells sense and respond to shear stress, but not in EPCs. Further study of EPC responses to shear stress will be necessary to better understand the physiological and pathophysiological roles of EPCs and
to apply EPCs to new therapies in the field of regenerative medicine.
The incidence of patients with refractory angina (RA) is increasing. Medical therapy for RA is limited and prognosis is poor. Experimental data suggest that the use of Extracorporeal shockwave myocardial revascularization (ESMR) may contribute to angiogenesis and improve symptoms of angina in patients with RA. Purpose of our study is to determine the efficacy of cardiac shock wave therapy (ESMR) in the management of patients with nonrevascolarized coronary artery disease (CAD).
We performed a prospective cohort study to examine the efficacy of ESMR applcation in patients with RA despite optimal medical therapy, not suitable for further PCI or CABG. Characteristics such as angina class scores (CCS class score), nitroglycerin consumption and hospitalization rate among cases (patients with RA who received ESMR) and controls (patients with RA who did not receive ESMR) were compared at baseline and 6months after ESMR therapy. In patients receiveing d ESMR the effect of on cardiac perfusion was assessed.
There were 43 patients in the case group and 29 patients in the control group. The mean age of the patients was 70±9.5years in the case group and 71±5.3years in the control group. Other characteristics (diabetes, coronary artery bypass graft, percutaneus coronary intervention, baseline CCS class score) were similar in both groups. There was a significant improvement in CCS class score (1.33±0.57 in cases and 1.92±0.69 in controls; p=0.0002), nitroglycerin consumption (20% in case cases, and 44.8% in controls; P<0.03) and hospitalization rate significantly reduced (13.9% in case cases, and 37.9% in controls; P<0.03). The patients who received ESMR, there was a significantly improvement in myocardial perfusion after 6months with a 33% relative reduction of summed stress score (SSS) (p=0.002).
This case control study demonstrates the beneficial effect of ESMR therapy on cardiac symptoms, myocardial perfusion and reduced hospitalization in patients with refractory angina. Ther current study supports a role for ESMR as a non-invasive therapuetic option for patients with RA.
Copyright © 2014 Elsevier Inc. All rights reserved.
Macrophages are tissue-resident immune cells that play a critical role in maintaining homeostasis and fighting infection. In addition, these cells are involved in the progression of many pathologies including cancer and atherosclerosis. In response to a variety of microenvironmental stimuli, macrophages can be polarized to achieve a spectrum of functional phenotypes. This review will discuss some emerging evidence in support of macrophage phenotypic regulation by physical and mechanical cues. As alterations in the physical microenvironment often underlie pathophysiological states, an understanding of their effects on macrophage phenotype and function may help provide mechanistic insights into disease pathogenesis.
Cells respond to mechanical signals, but the subcellular mechanisms are not well understood. The nucleus has recently emerged as an important mechanosensory organelle in the cell, as it is intimately connected to the cytoskeleton. Mechanical forces applied to cells that act on membrane-embedded receptors are transmitted through the cytoskeleton to the nuclear surface. Interfering with linkers of the nucleus to the cytoskeleton causes defects in cell mechanosensing and cell function. In this chapter, we discuss recent work in this area, highlighting the role that the nuclear linkages with the cytoskeleton play in cellular mechanotransduction.
In this work, the role of shock wave-induced increase of bone morphogenetic proteins in modulating the osteogenic properties of osteoblast-like cells seeded on a bioactive scaffold was investigated using gremlin as a bone morphogenetic protein antagonist. Bone-like glass-ceramic scaffolds, based on a silicate experimental bioactive glass developed at the Politecnico di Torino, were produced by the sponge replication method and used as porous substrates for cell culture. Human MG-63 cells, exposed to shock waves and seeded on the scaffolds, were treated with gremlin every two days and analysed after 20 days for the expression of osteoblast differentiation markers. Shock waves have been shown to induce osteogenic activity mediated by increased expression of alkaline phosphatase, osteocalcin, type I collagen, BMP-4 and BMP-7. Cells exposed to shock waves plus gremlin showed increased growth in comparison with cells treated with shock waves alone and, conversely, mRNA contents of alkaline phosphatase and osteocalcin were significantly lower. Therefore, the shock wave-mediated increased expression of bone morphogenetic protein in MG-63 cells seeded on the scaffolds is essential in improving osteogenic activity; blocking bone morphogenetic protein via gremlin completely prevents the increase of alkaline phosphatase and osteocalcin. The results confirmed that the combination of glass-ceramic scaffolds and shock waves exposure could be used to significantly improve osteogenesis opening new perspectives for bone regenerative medicine.
Introduction There is accumulating evidence for the effectiveness of extracorporeal shock wave therapy (ESWT) when treating lower limb tendinopathies including greater trochanteric pain syndrome (GTPS), patellar tendinopathy (PT) and Achilles tendinopathy (AT). The aim of this study was to evaluate the effectiveness of ESWT for lower limb tendinopathies
Methods PubMed (Medline), Embase, Web of Knowledge, Cochrane and CINAHL were searched from inception to February 2013 for studies of any design investigating the effectiveness of ESWT in GTPS, PT and AT. Citation tracking was performed using PubMed and Google Scholar. Animal and non-English language studies were excluded. Quality assessment was performed by two independent reviewers and effect size calculations were completed where sufficient data were provided.
Results 20 studies were identified with 13 providing sufficient data to complete effect size calculations. The energy level, number of impulses, number of sessions, and the use of local anaesthetic varied between studies. Evidence is limited by low participant numbers and methodological weaknesses including inadequate randomisation. Moderate evidence indicates ESWT is more effective than home training and corticosteroid injection in the short (<12 months) and long (>12 months) term for GTPS. Limited evidence indicates ESWT is more effective than alternative conservative managements including non-steroidal anti-inflammatory drugs, physiotherapy and an exercise programme and equal to patellar tenotomy surgery in the long term for PT [Furia, 2013]. Moderate evidence indicates ESWT is more effective than eccentric loading for insertional AT and equal to eccentric loading for mid-portion AT in the short term. Additionally, there is moderate evidence that combining ESWT and eccentric loading in mid-portion AT may produce superior outcomes to eccentric loading alone [Rompe, 09] (Figure 1).
Discussion ESWT can play a role in treatment of patients with lower limb tendinopathy alongside progressive load and flexibility management. Both forms of treatment serve to induce tendon regeneration with rehabilitation exercise tending to be carried out over a period of many weeks, whereas ESWT treatment is typically administered weekly for 3 weeks. A suitable pathway would be using ESWT as an initial starting treatment to be followed by an exercise programme, with some evidence that combined treatments confer additional benefit the effect is even greater. More robust RCTs with larger sample sizes and control groups that include objective functional tests are needed to build upon the limited/moderate evidence that currently exists for ESWTs effectiveness in lower limb tendinopathy. Additionally, further RCTs specifically comparing the different elements of ESWT – energy levels, number of applications and number of days between applications are needed to identify the optimum protocol.
References Furia et al. Knee Surg Sports Traumatol Arthrosc. 2013;21:346–50
Rompe et al. Am J Sports Med. 2009;37:463–70
Focused extracorporeal shock waves have been found to upregulate the expression of collagen and to initiate cell proliferation in healthy tenocytes and to positively affect the metabolism of tendons, promoting the healing process. Recently, soft-focused extracorporeal shock waves have also been found to have a significant effect on tissue regeneration. However, very few in vitro reports have dealt with the application of this type of shock wave to cells, and in particular, no previous studies have investigated the response of tendon cells to this impulse. We devised an original model to investigate the in vitro effects of soft-focused shock waves on a heterogeneous population of human resident tendon cells in adherent monolayer culture. Our results indicate that soft-focused extracorporeal shock wave treatment (0.17 mJ/mm2) is able to induce positive modulation of cell viability, proliferation and tendon-specific marker expression, as well as release of anti-inflammatory cytokines. This could prefigure a new rationale for routine employment of soft-focused shock waves to treat the failed healing status that distinguishes tendinopathies.
Background:
Because direct application of low-energy shock waves induces angiogenesis, we investigated the safety and efficacy of this new therapy to develop a noninvasive method of repeatable therapeutic angiogenesis for treating peripheral arterial disease (PAD).
Subjects and methods:
The subjects were 10 patients who had symptomatic PAD and limited ischemia in a below-the-knee artery. Low-energy shock waves were directly applied to the calf muscles 6 times every other day. Intracorporeal changes were evaluated with ultrasonography to determine adverse effects of therapy. To assess blood flow of the microcirculation, transcutaneous oxygen tension (TcPO2), skin perfusion pressure (SPP), and (99m)technetium-tetrofosmin ((99m)Tc-TF) scintigraphy were performed before and after therapy. The TcPO2 was measured while subjects inhaled pure oxygen (maximum TcPO2). The (99m)Tc-TF perfusion index was determined as a ratio of uptake in muscle to that in the brain (control) for quantitative analysis.
Results:
No adverse effects were noted in any patient. Maximum TcPO2 values increased significantly on the calf (57.3±28.4 to 71.0±14.5 mm Hg, p=0.044) and the dorsum of the foot (52.2±21.8 to 76.1±17.9 mm Hg, p=0.012). The SPP tended to increase after therapy on the dorsum and plantar surfaces of the foot, but the differences were not significant. The (99m)Tc-TF perfusion index in the foot significantly increased (0.48±0.09 to 0.61±0.12, p=0.0013), but that in the leg did not change.
Conclusion:
We have demonstrated that low-energy shock wave therapy is safe and can restore blood flow in the microcirculation in patients with symptomatic PAD.
Shock wave therapy (SWT) reportedly improves ventricular function in ischemic heart failure. Angiogenesis and inflammation modulatory effects were described. However, the mechanism remains largely unknown. We hypothesized that SWT modulates inflammation via toll-like receptor 3 (TLR3) through the release of cytosolic RNA. SWT was applied to human umbilical vein endothelial cells (HUVECs) with 250 impulses, 0.08 mJ/mm(2) and 3 Hz. Gene expression of TLR3, inflammatory genes and signalling molecules was analysed at different time points by real-time polymerase chain reaction. SWT showed activation of HUVECs: enhanced expression of TLR3 and of the transporter protein for nucleic acids cyclophilin B, of pro-inflammatory cytokines cyclophilin A and interleukin-6 and of anti-inflammatory interleukin-10. No changes were found in the expression of vascular endothelial cell adhesion molecule. SWT modulates inflammation via the TLR3 pathway. The interaction between interleukin (IL)-6 and IL-10 in TLR3 stimulation can be schematically seen as a three-phase regulation over time.
Extracorporeal shock wave has been used in the noninvasive treatment of various diseases including musculoskeletal disorders. In particular, shock wave with low energy level showed anti-inflammatory effect and increased angiogenesis in ischemic tissues. However, the detailed cellular pathway in endothelial signaling is not fully understood. We investigate the role of shock wave with low energy level in angiogenic gene expression and underlying molecular mechanism by comparing the laminar and oscillatory fluid shear stresses in endothelial cells.
We show that shock wave with low energy level (0.012-0.045mJ/mm(2)) stimulated phosphorylation of Akt, eNOS and Erk 1/2 in a time-dependent manner which is similar to the effect of laminar fluid shear stress. The transfection of endothelial cells with siRNA encoding VEGFR2, VE-cadherin and PECAM-1 inhibited shock wave-induced phosphorylation of Akt, eNOS and Erk 1/2 and angiogenic gene expressions, including Akt, eNOS, KLF2/4, and Nur77. Moreover, mechanical stimulation through extracorporeal shock wave induced endothelial cell migration and tube formation.
Our results demonstrate that shock wave-induced Akt/eNOS phosphorylation and angiogenic gene expression were mediated through the mechanosensory complex formation involving VEGFR-2, VE-cadherin and PECAM-1 which was similar to the effect of laminar shear stress.
'Shock wave' therapies are now extensively used in the treatment of musculoskeletal injuries. This systematic review summarises the evidence base for the use of these modalities.
A thorough search of the literature was performed to identify studies of adequate quality to assess the evidence base for shockwave therapies on pain in specific soft tissue injuries. Both focused extracorporeal shockwave therapy (F-ESWT) and radial pulse therapy (RPT) were examined.
23 appropriate studies were identified. There is evidence for the benefit of F-ESWT and of RPT in a number of soft tissue musculoskeletal conditions, and evidence that both treatment modalities are safe. There is evidence that F-ESWT is effective in the treatment of plantar fasciitis, calcific tendinitis, and that RPT is effective in plantar fasciitis. Where benefit is seen in F-ESWT, it appears to be dose dependent, with greater success seen with higher dose regimes. There is low level evidence for lack of benefit of low-dose F-ESWT and RPT in non-calcific rotator cuff disease and mixed evidence in lateral epicondylitis.
Human bone marrow stromal cells (hBMSCs) bear tremendous clinical potential due to their immunomodulatory properties in transplantation settings and their contribution to tissue regeneration. In fact, they are among the most promising types of stem-like cells for therapeutic applications and are the subject of intense research. However, the clinical use of hBMSCs has been confounded by limitations in their availability; they are scarce cells cumbersome to isolate and purify. Additionally, they are difficult to target to the site of injury in regeneration experiments. In order to combat these limitations, focused extracorporeal shock waves (fESW, 0.2/0.3mJ∗mm(-2)) were applied to purified, cultured hBMSCs. fESW (0.2mJ∗mm(-2)) stimulations were found to increase hBMSCs' growth rate (p<0.05), proliferation (p<0.05), migration, cell tracking and wound healing (p<0.05, respectively), as well as to reduce the rate of apoptosis activation (p<0.05). The increase in hBMSC migration behavior was found to be mediated by active remodeling of the actin cytoskeleton as indicated by increased directed stress fiber formations (p<0.05). Furthermore, hBMSCs maintain their differentiation potentials after fESW treatment, whereas 0.2mJ∗mm(-2) is the most effective application. In conclusion, our results establish first-timely that hBMSCs' behavior can be modified and optimized in response to defined mechanical stimulation. These findings appear particularly promising as they suggest that mechanical stress preconditions hBMSCs for improved therapeutic performance without genetic manipulations and that mechanically preconditioned hBMSCs will be advantageous for hBMSC-based tissue regeneration. Therefore, this approach opens the door for exploiting the full potential of these cells in regenerative medicine.
It has long been thought that the effectiveness and efficiency of physical therapy would improve if our understanding of the cell biology/biochemistry that participates in mechanics could be improved. Traditional physical therapy focuses primarily on rehabilitation, but recent developments in mechanobiology that illuminated the effects of physical forces on cells and tissues have led to the realization that the old therapy model should be updated. To achieve this here, the term mechanotherapy is proposed and recent studies showing how mechanotherapies target particular cells, molecules, and tissues are reviewed. These studies show how mechanical force modulates integrin-mediated processes and other mechanosensors such as gap junctions, hemichannels, primary cilia, transient receptor potential channels (cell targeting), and intracellular mechanosignaling pathways (molecule targeting). The role of mechanical force in various therapies, including microdeformation, shockwave, tissue expansion, distraction osteogenesis, and surgical tension reduction (tissue targeting) therapies, is reviewed. This review aims to jumpstart research into this field, which promises to generate a new era of viable and novel pharmacological and engineering interventions that can overcome human diseases.
Extracorporeal shock-wave (ESW) treatment hasbeen shown to be effective in promoting the healing of fractures. We aimed to determine whether ESW could enhance the growth of bone-marrow osteoprogenitor cells. We applied ESW to the left femur of rats 10 mm above the knee at 0.16 mJ/mm ² in a range of between 250 and 2000 impulses. Bone-marrow cells were harvested after ESW for one day and subjected to assessment of colony-forming unit (CFU) granulocytes, monocytes, erythocytes, megakaryocytes (CFU-Mix), CFU-stromal cells (CFU-S) and CFU-osteoprogenitors (CFU-O).
We found that the mean value for the CFU-O colonies after treatment with 500 impulses of ESW was 168.2 CFU-O/well (sem 11.3) compared with 88.2 CFU-O/well (sem 7.2) in the control group. By contrast, ESW treatment did not affect haematopoiesis as shown by the CFU-Mix (p = 0.557). Treatment with 250 and 500 impulses promoted CFU-O, but not CFU-Mix formations whereas treatment with more than 750 impulses had an inhibiting effect. Treatment with 500 impulses also enhanced the activity of bone alkaline phosphatase in the subculture of CFU-O (p< 0.01), indicating a selective promotion of growth of osteoprogenitor cells. Similarly, formation of bone nodules in the long-term culture of bone-marrow osteoprogenitor cells was also significantly enhanced by ESW treatment with 500 impulses. The mean production of TGF-β1 was 610 pg/ml (sem 84.6) in culture supernatants from ESW-treated rats compared with 283 pg/ml (sem 36.8) in the control group.
Our findings suggest that optimal treatment with ESW could enhance rat bone-marrow stromal growth and differentiation towards osteoprogenitors presumably by induction of TGF-β1.
Objectives:
Shock waves have been shown to induce recruitment of intravenously injected endothelial progenitor cells to ischemic hind limbs in rats. We hypothesized that shock wave treatment as sole therapy would induce angiogenesis in this ischemia model and would lead to mobilization of endogenous endothelial (progenitor) cells.
Methods:
A total of 18 rats, aged 5 weeks old, were subdivided into 3 groups: sham (n = 6), ischemic muscle with shock wave treatment (shock wave treatment group, n = 6), and without shock wave treatment (control, n = 6). Hind limb ischemia was induced by ligation of the femoral artery. Three weeks later, shock wave treatment (300 impulses at 0.1 mJ/mm(2)) was applied to the adductor muscle; the controls were left untreated. Muscle samples were analyzed using real-time polymerase chain reaction for angiogenic factors and chemoattractants for endothelial progenitor cell mobilization. Fluorescence activated cell sorting analysis of the peripheral blood was performed for CD31/CD34-positive cells. Perfusion was measured using laser Doppler imaging. Functional improvement was evaluated by walking analysis.
Results:
Angiogenic factors/endothelial progenitor cell chemoattractants, stromal cell-derived factor-1 and vascular endothelial growth factor, were increased in the treatment group, as shown by real-time polymerase chain reaction, indicating the mobilization of endothelial progenitor cells. Fluorescence activated cell sorting analysis of the peripheral blood revealed high numbers of CD31/CD34-positive cells in the treatment group. Greater numbers of capillaries were found in the treated muscles. Blood perfusion increased markedly in the treatment group and led to functional restoration, as shown by the results from the walking analysis.
Conclusions:
Shock wave therapy therefore could develop into a feasible alternative to stem cell therapy in regenerative medicine, in particular for ischemic heart and limb disease.
Mononuclear phagocyte plasticity includes the expression of functions related to resolution of inflammation, tissue repair and remodelling, in particular when these cells are set in an M2 or an M2-like activation mode. Macrophages are credited with an essential role in remodelling during ontogenesis. In extraembryonic life, under homeostatic conditions, the macrophage trophic and remodelling functions are recapitulated in tissues such as the bone, mammary gland, decidua and placenta. In pathology, macrophages are key components of tissue repair and remodelling that occurs during wound healing, allergy, parasite infection and cancer. Interaction with cells bearing stem or progenitor cell properties is likely an important component of the role of macrophages in repair and remodelling. These properties of cells of the monocyte-macrophage lineage may represent a tool and a target for therapeutic exploitation. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Extracorporeal shock waves in orthopaedics are currently applied in the treatment of chronic enthesiopathies such as lateral epicondylitis, plantar heel spur, as well as in calcifying tendinitis of the shoulder or in bony nonunions. Detailed knowledge of physical parameters and properties of shock waves appear to be necessary to determine clinically relevant dose-effect relations and to make shock wave devices, clinical results, and basic science in shock wave therapy more comparable.
This study gives an overview of physical parameters and properties in shock wave therapy. Measurement technologies, types of shock wave devices, and mechanisms of shock waves are also described.
Extracorporeal shock waves have revolutionized urological stone treatment. Nowadays shock waves are widely used in orthopedics, too. This article reviews the applications of extracorporeal shock waves on bone and adjacent soft tissue. The osteoneogenetic effect of extracorporeal shock waves has heen proven and can be used to treat pseudarthrosis with a success rate of around 75%. Shock waves have a positive effect in tennis and golfer's elbow, calcaneal spur, and the complex called 'periarthritis humeroscapularis'. The mechanism for this is not yet known, and results from large prospective and randomized studies are still lacking. However, the treatment has been performed many thousands of times. In patients in whom conservative treatment has failed surgery used to be the only choice, but its success rate barely exceeds that of shock wave therapy and surgery can still be done if shock wave therapy fails. Extracorporeal shock waves will have an impact on orthopedics comparable to its effect in urology. Scientific evaluations, professional certifications, quality assurance and reimbursement issues present great challenges.
For almost 30 years, extracorporeal shock wave therapy has been clinically implemented as an effective treatment to disintegrate urinary stones. This technology has also emerged as an effective noninvasive treatment modality for several orthopedic and traumatic indications including problematic soft tissue wounds. Delayed/nonhealing or chronic wounds constitute a burden for each patient affected, significantly impairing quality of life. Intensive wound care is required, and this places an enormous burden on society in terms of lost productivity and healthcare costs. Therefore, cost-effective, noninvasive, and efficacious treatments are imperative to achieve both (accelerated and complete) healing of problematic wounds and reduce treatment-related costs. Several experimental and clinical studies show efficacy for extracorporeal shock wave therapy as means to accelerate tissue repair and regeneration in various wounds. However, the biomolecular mechanism by which this treatment modality exerts its therapeutic effects remains unclear. Potential mechanisms, which are discussed herein, include initial neovascularization with ensuing durable and functional angiogenesis. Furthermore, recruitment of mesenchymal stem cells, stimulated cell proliferation and differentiation, and anti-inflammatory and antimicrobial effects as well as suppression of nociception are considered important facets of the biological responses to therapeutic shock waves. This review aims to provide an overview of shock wave therapy, its history and development as well as its current place in clinical practice. Recent research advances are discussed emphasizing the role of extracorporeal shock wave therapy in soft tissue wound healing.
Extensive wounds of burn patients remain a challenge due to wound infection and subsequent septicemia. We wondered whether extracorporeal shock wave application (ESWA) accelerates the healing process. The aim of the study was to analyze microcirculation, angiogenesis and leukocyte endothelium interaction after burns by using ESWA with two types of low intensity.
Full-thickness burns were inflicted to the ears of hairless mice (n=51; area: 1.3mm(2)). The mice were randomized into five groups: (A) low-energy shock waves after burn injury (0.04mJ/mm(2)); (B) very low-energy shock waves after burn injury (0.015mJ/mm(2)); (C) mice received burns but no ESWA (control group); (D) mice without burn were exposed to low-energy shock waves; (E) mice without burns and with no shock wave application. Intravital fluorescent microscopy was used to assess microcirculatory parameters, angiogenesis and leukocyte behavior. ESWA was performed on day 1, 3 and 7 (500 shoots, 1Hz). Values were obtained straight after and on days 1, 3, 7 and 12 post burn.
Group A showed accelerated angiogenesis (non-perfused area at day 12: 5.3% vs. 9.1% (group B) and 12.6% (group C), p=0.005). Both shock wave groups showed improved blood flow after burn compared to group C. Shock waves significantly increased the number of rolling leukocytes compared to the non-ESWA-treated animals (group D: 210.8% vs. group E: 83.3%, p=0.017 on day 7 and 172.3 vs. 90.9%, p=0.01 on day 12).
Shock waves have a positive effect on several parameters of wound healing after burns, especially with regard to angiogenesis and leukocyte behaviour. In both ESWA groups, angiogenesis and blood flow outmatched the control group. Within the ESWA groups the higher intensity (0.04mJ/mm(2)) showed better results than the lower intensity group. Moreover, shock waves increased the number of rolling and sticking leukocytes as a part of an improved metabolism.
Peyronie's disease (PD) is a connective tissue disorder characterized by a fibrous plaque involving the tunica albuginea of the penis. The inelastic fibrous plaque leads to a penile curvature. Several Authors have suggested an immunological genesis of this disease, others have linked PD with Dupuytren's contracture. Signs of this disease are curvature, penile pain, penile deformity, difficulty with coitus, shortening, hinging, narrowing and erectile dysfunction. The natural history of PD and the clinical course can develop from spontaneous resolution of symptoms to progressive penile deformity and impotence. Surgical treatment is indicated when patients fail the conservative medical treatment and however, only in case of disease stabilization with a condition of impossibility of penetration. The medical treatment is indicated in the development stage of PD for at least one year after diagnosis and whenever in case of penile pain. Current non-surgical therapy includes vitamin-E, verapamil, para-aminobenzoate, propoleum, colchicine, carnitine, tamoxifen, interferons, collagenase, hyaluronidase, cortisone, pentoxifylline, superoxide dismutase, iontophoresis, radiation, extracorporeal shock wave therapy (ESWT) and the penile extender. The etiology of this fibrotic disease is not widely known, although in recent years pathophysiological knowledge has evolved and new studies propose the penile trauma as cause of the disease. The penile trauma results in a delamination of the tunica albuginea with a consequent small hematoma, then the process evolves as an inflammation with accumulation of inflammatory cells and production of reactive oxygen species (ROS). In the course of the inflammation, Peyronie's disease occurs due to the activation of nuclear factor kappa-B, that induces the production of inducible nitric oxide synthase (iNOS), with an increase of nitric oxide, leading to increased production of peroxynitrite anion. All these processes result in the proliferation of fibroblasts and myo-fibroblasts and excessive production of collagen between the layers of the tunica albuginea (penile plaque). Referring to the current knowledge of inflammatory and oxidative mechanisms of PD, a possible therapeutic strategy is then analyzed.
Multiple senses, including hearing, touch and osmotic regulation, require the ability to convert force into an electrical signal: A process called mechanotransduction. Mechanotransduction occurs through specialized proteins that open an ion channel pore in response to a mechanical stimulus. Many of these proteins remain unidentified in vertebrates, but known mechanotransduction channels in lower organisms provide clues into their identity and mechanism. Bacteria, fruit flies and nematodes have all been used to elucidate the molecules necessary for force transduction. This chapter discusses many different mechanical senses and takes an evolutionary approach to review the proteins responsible for mechanotransduction in various biological kingdoms.