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Translational Research in Shock Wave Medicine
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Translational Research in Shock Wave Medicine

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 50230

Special Issue Editors

Dr. Yao-Chi Chuang

E-Mail Website
Guest Editor
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan
Interests: shock wave medicine; translational research of bladder dysfunction
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Chang-Chun Hsiao

E-Mail Website
Guest Editor
1. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
2. Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
Interests: shockwave medicine; epigenetics; genomic medicine; cancer science

Special Issue Information

Dear Colleagues,

Shock waves (SWs) are acoustic waves that carry energy from an area of positive pressure to an area of negative pressure and induce a cavitation effect and a mechanical shear force on the target tissue, which is followed by some molecular changes and biological effects. The energy associated with SWs is used for various applications in medical science. High-energy extracorporeal SW therapy has been widely used to disintegrate urolithiasis for 30 years. However, SWs at low-energy levels induce a series of cell signaling pathways and activate various biological processes, such as anti-inflammation, angiogenesis, cell proliferation, inhibition of apoptosis, and peripheral nerve regeneration, depending on individual tissue type and condition. Low energy shock wave (LESW) therapy has been used clinically to treat musculoskeletal disorders, ischemic cardiovascular disorders, erectile dysfunction, and chronic pelvic pain syndrome through the mechanisms of neovascularization, tissue regeneration, and anti-inflammation. Furthermore, LESW has been proposed to temporarily increase tissue permeability and facilitate drug delivery.

In addition, SWs can be used in combination with other treatment modalities to achieve more effective methods of curing some of the most treatment-resistant entities in medicine. The scope of medical applications for extracorporeal shock waves continues to grow and become more popular as our understanding of the mechanisms behind their diverse therapeutic effects increases.

This Special Issue on “Translational Research in Shock Wave Medicine” will provide review and original articles to advance our knowledge of SWs in medical use and might inspire more discoveries for new medical applications for SWs. 

Dr. Yao-Chi Chuang
Prof. Dr. Chang-Chun Hsiao
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • shock wave
  • medicine
  • tissue regeneration
  • anti-inflammation
  • drug delivery

Published Papers (17 papers)

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27 pages, 3955 KiB  
Article
ESWT Diminishes Axonal Regeneration following Repair of the Rat Median Nerve with Muscle-In-Vein Conduits but Not after Autologous Nerve Grafting
by Johannes C. Heinzel, Viola Oberhauser, Claudia Keibl, Barbara Schädl, Nicole V. Swiadek, Gregor Längle, Helen Frick, Cyrill Slezak, Cosima Prahm, Johannes Grillari, Jonas Kolbenschlag and David Hercher
Biomedicines 2022, 10(8), 1777; https://doi.org/10.3390/biomedicines10081777 - 22 Jul 2022
Cited by 1 | Viewed by 2251
Abstract
Investigations reporting positive effects of extracorporeal shockwave therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT [...] Read more.
Investigations reporting positive effects of extracorporeal shockwave therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT after repair of the rat median nerve with either autografts (ANGs) or MVCs. In male Lewis rats, a 7 mm segment of the right median nerve was reconstructed either with an ANG or an MVC. For each reconstructive technique, one group of animals received one application of ESWT while the other rats served as controls. The animals were observed for 12 weeks, and nerve regeneration was assessed using computerized gait analysis, the grasping test, electrophysiological evaluations and histological quantification of axons, blood vessels and lymphatic vasculature. Here, we provide for the first time a comprehensive analysis of ESWT effects on nerve regeneration in a rat model of median nerve injury. Furthermore, this study is among the first reporting the quantification of lymphatic vessels following peripheral nerve injury and reconstruction in vivo. While we found no significant direct positive effects of ESWT on peripheral nerve regeneration, results following nerve repair with MVCs were significantly inferior to those after ANG repair. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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22 pages, 3983 KiB  
Article
Effects of Extracorporeal Shockwave Therapy on Functional Recovery and Circulating miR-375 and miR-382-5p after Subacute and Chronic Spinal Cord Contusion Injury in Rats
by Mohamed Ashmwe, Katja Posa, Alexander Rührnößl, Johannes Christoph Heinzel, Patrick Heimel, Michael Mock, Barbara Schädl, Claudia Keibl, Sebastien Couillard-Despres, Heinz Redl, Rainer Mittermayr and David Hercher
Biomedicines 2022, 10(7), 1630; https://doi.org/10.3390/biomedicines10071630 - 07 Jul 2022
Cited by 2 | Viewed by 2694
Abstract
Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT—applied [...] Read more.
Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT—applied within the subacute and chronic phase of SCI (spinal cord injury) on recovery in a rat spinal cord contusion model. Outcomes were evaluated by gait analysis, µCT and histological analysis of spinal cords. A panel of serum-derived miRNAs after SCI and after ESWT was investigated to identify injury-, regeneration- and treatment-associated expression patterns. Rats receiving ESWT showed significant improvement in motor function in both a subacute and a chronic experimental setting. This effect was not reflected in changes in morphology, µCT-parameters or histological markers after ESWT. Expression analysis of various miRNAs, however, revealed changes after SCI and ESWT, with increased miR-375, indicating a neuroprotective effect, and decreased miR-382-5p potentially improving neuroplasticity via its regulatory involvement with BDNF. We were able to demonstrate a functional improvement of ESWT-treated animals after SCI in a subacute and chronic setting. Furthermore, the identification of miR-375 and miR-382-5p could potentially provide new targets for therapeutic intervention in future studies. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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16 pages, 1573 KiB  
Article
A Comparative Feasibility Study for Transcranial Extracorporeal Shock Wave Therapy
by Cyrill Slezak, Jonas Flatscher and Paul Slezak
Biomedicines 2022, 10(6), 1457; https://doi.org/10.3390/biomedicines10061457 - 20 Jun 2022
Cited by 3 | Viewed by 1807
Abstract
The potential beneficial regenerative and stimulatory extracorporeal shock wave therapy (ESWT) applications to the central nervous system have garnered interest in recent years. Treatment zones for these indications are acoustically shielded by bones, which heavily impact generated sound fields. We present the results [...] Read more.
The potential beneficial regenerative and stimulatory extracorporeal shock wave therapy (ESWT) applications to the central nervous system have garnered interest in recent years. Treatment zones for these indications are acoustically shielded by bones, which heavily impact generated sound fields. We present the results of high-resolution tissue-realistic simulations, comparing the viability of different ESWT applicators in their use for transcranial applications. The performances of electrohydraulic, electromagnetic, and piezoelectric transducers for key reflector geometries are compared. Based on density information obtained from CT imaging of the head, we utilized the non-linear wave propagation toolset Matlab k-Wave to obtain spatial therapeutic sound field geometries and waveforms. In order to understand the reliability of results on the appropriate modeling of the skull, three different bone attenuation models were compared. We find that all currently clinically ESWT applicator technologies show significant retention of peak pressures and energies past the bone barrier. Electromagnetic transducers maintain a significantly higher energy flux density compared to other technologies while low focusing strength piezoelectric applicators have the weakest transmissions. Attenuation estimates provide insights into sound field degradation and energy losses, indicating that effective transcranial therapies can readily be attained with current applicators. Furthermore, the presented approach will allow for future targeted in silico development and the design of applicators and therapy plans to ultimately improve therapeutic outcomes. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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17 pages, 2987 KiB  
Article
Exploiting Shock Waves to Trigger the Anticancer Sonodynamic Activity of 5-Aminolevulinc Acid-Derived Protoporphyrin IX on In Vitro 2D and 3D Cancer Models
by Federica Foglietta, Patrizia Panzanelli, Loredana Serpe and Roberto Canaparo
Biomedicines 2022, 10(3), 615; https://doi.org/10.3390/biomedicines10030615 - 06 Mar 2022
Cited by 5 | Viewed by 2198
Abstract
Sonodynamic therapy (SDT) is a noninvasive method for cancer treatment based on selective activation of a sonosensitiser by ultrasound (US), which results in the generation of reactive oxygen species (ROS) and cancer cell death. SDT uses a similar approach to photodynamic therapy (PDT), [...] Read more.
Sonodynamic therapy (SDT) is a noninvasive method for cancer treatment based on selective activation of a sonosensitiser by ultrasound (US), which results in the generation of reactive oxygen species (ROS) and cancer cell death. SDT uses a similar approach to photodynamic therapy (PDT), but can overcome the main drawback of PDT, i.e., poor tissue penetration of light. This research work investigated the anticancer effect of SDT on various two- (2D) and three-dimensional (3D) in vitro tumour models, using PDT as a reference treatment. Sonodynamic experiments were performed with pulsed US, specifically with shock waves (SW) and the prodrug 5-aminolevulinic acid (Ala), which is converted—at the mitochondrial level—into the sonosensitiser protoporphyrin IX (PPIX). SW-mediated PPIX sonodynamic activation resulted in a significant decrease in cell proliferation, especially on human fibrosarcoma (HT-1080) cells, where PPIX accumulation was higher compared to human melanoma (A2058) and neuroblastoma (SH-SY5 Y) cells. Moreover, SW-mediated SDT showed significant ROS generation, cell line-dependent in its amount, probably due to differences in Ala-induced PPIX synthesis. In all cancer cell lines, apoptosis was highlighted as the main cancer cell death pathway determined by SW-mediated SDT, along with significant cytochrome c release, and a consequent increase in DNA damage. The efficacy of SDT with SW and Ala in halting cancer cell proliferation was also confirmed in 3D cancer spheroids. The present study suggests that SW-mediated SDT is a valuable approach to slow down tumour proliferation, thus opening an innovative scenario in cancer treatment. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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15 pages, 2235 KiB  
Article
Shock Waves Enhance Expression of Glycosphingolipid Tumor Antigen on Renal Cell Carcinoma: Dynamics of Physically Unmasking Hidden Intracellular Markers Independent of Gene-Signaling Pathways
by Nushin Hosano, Zahra Moosavi-Nejad, Makoto Satoh and Hamid Hosano
Biomedicines 2022, 10(3), 545; https://doi.org/10.3390/biomedicines10030545 - 24 Feb 2022
Viewed by 1458
Abstract
Antigens associated with tumors have proven valuable in cancer immunotherapy. Their insufficient expression in the majority of tumors, however, limits their potential value as therapeutic markers. Aiming for a noninvasive approach applicable in clinical practice, we investigated the possibility of using focused shock [...] Read more.
Antigens associated with tumors have proven valuable in cancer immunotherapy. Their insufficient expression in the majority of tumors, however, limits their potential value as therapeutic markers. Aiming for a noninvasive approach applicable in clinical practice, we investigated the possibility of using focused shock waves to induce membrane expression of hidden intracellular tumor markers. Here, we studied the in vitro effect of a thousand focused shock waves at 16 MPa overpressure on the membrane expression of a cytosolic glycosphingolipid, monosialosyl-galactosyl-globoside (MSGG). Double-staining flow cytometry with propidium-iodide and monoclonal antibody RM1 revealed an immediate increase in MSGG expression on renal carcinoma cells (18% ± 0.5%) that reached its peak value (20.73% ± 0.4%) within one hour after the shock waves. The results of immunoelectron microscopy confirmed the incorporation of MSGG into newly formed cytosolic vesicles and their integration with the cell membrane. Based on the enzymatic nature of MSGG production that is not controlled directly by genes, the immediate upregulation of MSGG membrane expression implies that a chain of mechanochemical events affecting subcellular structures are responsible for the shock-wave-induced antigenic modification. Physically unmasking hidden tumor antigens and enhancing their expression by focused shock waves presents a potential noninvasive method of boosting tumor immunogenicity as a theranostic strategy in cancer immunotherapy. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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21 pages, 59104 KiB  
Article
Extracorporeal Shock Wave Therapy Combined with Platelet-Rich Plasma during Preventive and Therapeutic Stages of Intrauterine Adhesion in a Rat Model
by Yin-Hua Cheng, Ni-Chin Tsai, Yun-Ju Chen, Pei-Ling Weng, Yun-Chiao Chang, Jai-Hong Cheng, Jih-Yang Ko, Hong-Yo Kang and Kuo-Chung Lan
Biomedicines 2022, 10(2), 476; https://doi.org/10.3390/biomedicines10020476 - 17 Feb 2022
Cited by 7 | Viewed by 4339
Abstract
Intrauterine adhesion (IUA) is caused by artificial endometrial damage during intrauterine cavity surgery. The typical phenotype involves loss of spontaneous endometrium recovery and angiogenesis. Undesirable symptoms include abnormal menstruation and infertility; therefore, prevention and early treatment of IUA remain crucial issues. Extracorporeal shockwave [...] Read more.
Intrauterine adhesion (IUA) is caused by artificial endometrial damage during intrauterine cavity surgery. The typical phenotype involves loss of spontaneous endometrium recovery and angiogenesis. Undesirable symptoms include abnormal menstruation and infertility; therefore, prevention and early treatment of IUA remain crucial issues. Extracorporeal shockwave therapy (ESWT) major proposed therapeutic mechanisms include neovascularization, tissue regeneration, and fibrosis. We examined the effects of ESWT and/or platelet-rich plasma (PRP) during preventive and therapeutic stages of IUA by inducing intrauterine mechanical injury in rats. PRP alone, or combined with ESWT, were detected an increased number of endometrial glands, elevated vascular endothelial growth factor protein expression (hematoxylin-eosin staining and immunohistochemistry), and reduced fibrosis rate (Masson trichrome staining). mRNA expression levels of nuclear factor-kappa B, tumor necrosis factor-α, transforming growth factor-β, interleukin (IL)-6, collagen type I alpha 1, and fibronectin were reduced during two stages. However, PRP alone, or ESWT combined with PRP transplantation, not only increased the mRNA levels of vascular endothelial growth factor (VEGF) and progesterone receptor (PR) during the preventive stage but also increased PR, insulin-like growth factor 1 (IGF-1), and IL-4 during the therapeutic stage. These findings revealed that these two treatments inhibited endometrial fibrosis and inflammatory markers, thereby inhibiting the occurrence and development of intrauterine adhesions. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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12 pages, 3315 KiB  
Article
Comparison of Extracorporeal Shockwave Therapy with Non-Steroid Anti-Inflammatory Drugs and Intra-Articular Hyaluronic Acid Injection for Early Osteoarthritis of the Knees
by Shun-Wun Jhan, Ching-Jen Wang, Kuan-Ting Wu, Ka-Kit Siu, Jih-Yang Ko, Wen-Chiung Huang, Wen-Yi Chou and Jai-Hong Cheng
Biomedicines 2022, 10(2), 202; https://doi.org/10.3390/biomedicines10020202 - 18 Jan 2022
Cited by 3 | Viewed by 3877
Abstract
Conservative treatments for early osteoarthritis (OA) of the knee included the use of non-steroid anti-inflammatory drugs (NSAIDs) and intra-articular hyaluronic acid (HA) injection. Recently, several animal studies reported that extracorporeal shockwave therapy (ESWT) demonstrated chondroprotective effects on knee OA. The present study compared [...] Read more.
Conservative treatments for early osteoarthritis (OA) of the knee included the use of non-steroid anti-inflammatory drugs (NSAIDs) and intra-articular hyaluronic acid (HA) injection. Recently, several animal studies reported that extracorporeal shockwave therapy (ESWT) demonstrated chondroprotective effects on knee OA. The present study compared the efficacy of oral NSAIDs, HA injection, and noninvasive ESWT for early OA of the knee. Forty-five patients with early knee OA were randomized into three groups. NSAIDs group received celecoxib 200 mg daily for 3 weeks. HA group received intra-articular injection of HA once a week for 3 weeks. ESWT group received ESWT for 3 sessions at bi-weekly interval. All patients were followed up for one year. Evaluations included the visual analogue scale (VAS) score, serum enzyme-linked immunosorbent assay (ELISA), plain radiography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI). In addition, the functional scores were performed including, WOMAC (Western Ontario and McMaster Universities Arthritis Index) score, KOOS (knee injury and osteoarthritis outcome) score, and IKDC (International Knee Documentation Committee) score. All three groups showed significant improvement in VAS and functional scores as well as in the collected one-year follow-up data after treatments. ESWT group had better pain relief than NSAIDs and HA groups. ESWT group had better therapeutic effects in the functional scores than NSAIDs and HA groups. The bone mineral density (BMD) of proximal tibia is significantly increased after ESWT than others. In the serum ELISA, ESWT inhibited the expression of COMP in knee OA patients as compared with NSAIDs and HA groups. The parameters of MRI showed no significant differences between three groups after treatments. ESWT and intra-articular HA injection showed comparable results than NSAIDs. ESWT was superior in pain relief than HA and NSAIDs. The results demonstrated that ESWT was an effective and alternative therapy than HA and NSAIDs for early osteoarthritis of the knees. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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18 pages, 11403 KiB  
Article
Extracorporeal Shock Wave Therapy Salvages Critical Limb Ischemia in B6 Mice through Upregulating Cell Proliferation Signaling and Angiogenesis
by Pei-Hsun Sung, Tsung-Cheng Yin, Han-Tan Chai, John Y. Chiang, Chih-Hung Chen, Chi-Ruei Huang and Hon-Kan Yip
Biomedicines 2022, 10(1), 117; https://doi.org/10.3390/biomedicines10010117 - 06 Jan 2022
Cited by 7 | Viewed by 1703
Abstract
(1) This study tests hypothesis whether extracorporeal shock wave (ECSW) therapy effectively salvages mouse critical limb ischemia (CLI). In vitro result demonstrated that the angiogenesis parameters (i.e., tubular length/cluster/network formation) and protein expressions of EGFR/VEGFR2/RAS/c-Raf/MEK/ERK/VEGF/p-PI3K/p-Akt/p-m-TOR were significantly and progressively increased with stepwise augmentation [...] Read more.
(1) This study tests hypothesis whether extracorporeal shock wave (ECSW) therapy effectively salvages mouse critical limb ischemia (CLI). In vitro result demonstrated that the angiogenesis parameters (i.e., tubular length/cluster/network formation) and protein expressions of EGFR/VEGFR2/RAS/c-Raf/MEK/ERK/VEGF/p-PI3K/p-Akt/p-m-TOR were significantly and progressively increased with stepwise augmentation of ECSW energy (0.1/0.14/0.20 mJ/mm2/140 impulses). On the other hand, they were suppressed by administration of Avastin (20 μM). Adult male B6 mice (n = 24) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 [CLI + ECSW (0.12 mJ/mm2/120 impulses/at days 1/3/7 after CLI induction)] and group 4 [CLI + ECSW (0.12 mJ/mm2/120 impulses) + Avastin (1 mg/intramuscular-injection)] at days 1/3/7 after CLI induction] and quadriceps were harvested by day 14. The laser Doppler result showed that the ratio of left (ischemia) to right (normal) limb blood flow was highest in group 1, lowest in group 2, and significantly higher in group 3 than in group 4 by days 7/14 after the CLI procedure (p < 0.0001). The protein expressions of cell proliferation/migration/angiogenesis receptors (EGFR/VEGFR2), angiogenesis biomarkers (VEGF/CXCR4/SDF-1) and cell proliferation/growth/survival (Ras/c-Raf/MEK/ERK)/(PI3K/Akt/m-TOR) and cell motility/proliferation (p-FAK/p-Scr) signaling biomarkers were significantly higher in group 3 than in groups 1/2/4, and significantly lower in group 1 than in groups 2/4, but they did not show a difference between groups 2 and 4 (all p < 0.001). The small vessel density and cellular levels of endothelial cell surface marker (CD31+) exhibited an identical pattern of blood flow, whereas the angiogenesis (CXCR4+/VEGF+) displayed an identical pattern of VEGFR2 among the groups (all p < 0.0001). The in vitro and in vivo studies found ECSW salvaged the CLI mainly through upregulating Ras-Raf-MEK/ERK/cell motility, cell proliferation/growth pathways and angiogenesis. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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17 pages, 15679 KiB  
Article
Adipose-Derived Mesenchymal Stem Cells-Conditioned Medium Modulates the Expression of Inflammation Induced Bone Morphogenetic Protein-2, -5 and -6 as Well as Compared with Shockwave Therapy on Rat Knee Osteoarthritis
by Jai-Hong Cheng, Chieh-Cheng Hsu, Shan-Ling Hsu, Wen-Yi Chou, Yi-No Wu, Chun-En Aurea Kuo, Tsai-Chin Hsu, Li-Yen Shiu and Shun-Wun Jhan
Biomedicines 2021, 9(10), 1399; https://doi.org/10.3390/biomedicines9101399 - 05 Oct 2021
Cited by 10 | Viewed by 2370
Abstract
The dose-dependent effects of adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) were compared with those of shockwave (SW) therapy in the treatment of early osteoarthritis (OA). Anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was performed in rats divided into sham, OA, SW, [...] Read more.
The dose-dependent effects of adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) were compared with those of shockwave (SW) therapy in the treatment of early osteoarthritis (OA). Anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was performed in rats divided into sham, OA, SW, CM1 (intra-articular injection of 100 μL ADSC-CM into knee OA), and CM2 (intra-articular injection of 200 μL ADSC-CM) groups. Cartilage grading, grading of synovium changes, and specific molecular analysis by immunohistochemistry staining were performed. The OARSI and synovitis scores of CM2 and SW group were significantly decreased compared with those of the OA group (p < 0.05). The inflammatory markers interleukin 1β, terminal deoxynucleotidyl transferase dUTP nick end labeling and matrix metalloproteinase 13 were significantly reduced in the CM2 group compared to those in the SW and CM1 groups (p < 0.001). Cartilage repair markers (type II collagen and SRY-box transcription factor 9, SOX9) expression were significantly higher in the CM2 group than in the other treatment groups (p < 0.001; p < 0.05). Furthermore, inflammation-induced growth factors such as bone morphogenetic protein 2 (BMP2), BMP5, and BMP6 were significantly reduced in the treatment groups, and the CM2 group showed the best results among the treatments (p < 0.05). In conclusion, ADSC-CM and SW ameliorated the expression of inflammatory cytokines and inflammation-induced BMPs to protect the articular cartilage of the OA joint. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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18 pages, 5083 KiB  
Article
Extracorporeal Shock Wave Therapy Protected the Functional and Architectural Integrity of Rodent Urinary Bladder against Ketamine-Induced Damage
by Yen-Ta Chen, Kuan-Hui Huang, John Y. Chiang, Pei-Hsun Sung, Chi-Ruei Huang, Yi-Ching Chu, Fei-Chi Chuang and Hon-Kan Yip
Biomedicines 2021, 9(10), 1391; https://doi.org/10.3390/biomedicines9101391 - 04 Oct 2021
Cited by 3 | Viewed by 2126
Abstract
This study tested the hypothesis that extracorporeal-shock-wave (ECSW) protected the functional and anatomical integrity of rat urinary-bladder against ketamine-induced damage. In in vitro study, the rat bladder smooth muscle cells (RBdSMCs) were categorized into G1 (sham-control), G2 (RBdSMCs + menadione), G3 (RBdSMCs + [...] Read more.
This study tested the hypothesis that extracorporeal-shock-wave (ECSW) protected the functional and anatomical integrity of rat urinary-bladder against ketamine-induced damage. In in vitro study, the rat bladder smooth muscle cells (RBdSMCs) were categorized into G1 (sham-control), G2 (RBdSMCs + menadione), G3 (RBdSMCs + ECSW) and G4 (RBdSMCs + menadione + ECSW). The results showed protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), inflammatory markers (MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-6/IL-1ß/MMP-9/iNOS), and cell-stress response signalings (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38/p-53) were significantly increased in G2 than in G1 and G3, and those were significantly reversed in G4 (all p < 0.0001). Adult-male SD rats (n = 24) were equally categorized into group 1 (sham-control), group 2 (ketamine/30 mg/kg/daily i.p. injection for four weeks), group 3 [ketamine/30 mg/kg + ECSW/optimal energy (0.12 mJ/mm2/120 impulses/at 3 h and days 3/7/14/21/28 after ketamine administration)] and group 4 [(ketamine/30 mg/kg + ECSW/higher energy (0.16 mJ/mm2/120 impulses)] and animals were euthanized by day 42. The results showed the urine levels of pro-inflammatory cytokines (TNF-α/IL-6) were lowest in group 1, highest in group 2 and significantly higher in group 3 than in group 4 at days 1/7/14/28 (all p < 0.0001). The duration of urinary bladder contraction was lowest in group 2, highest in group 1 and significantly higher in group 4 than in group 3, whereas the maximal pressure of urinary bladder exhibited an opposite pattern of bladder contraction among the groups (all p < 0.0001). The histopathological findings of fibrosis/inflammation/keratinization and protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), and inflammatory (TLR-2/TLR-4/MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-1ß/MMP-9/iNOS) and cell-stress response (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38) signalings and apoptotic/fibrotic biomarkers (cleaved-caspas3/cleaved-PARB/Smad3/TFG-ß) exhibited an identical pattern of urine proinflammatory cytokine among the groups (all p < 0.0001). ECSW effectively attenuated ketamine-induced bladder damage and dysfunction. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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21 pages, 5616 KiB  
Article
Extracorporeal Shock Wave Enhanced Exogenous Mitochondria into Adipose-Derived Mesenchymal Stem Cells and Further Preserved Heart Function in Rat Dilated Cardiomyopathy
by Pei-Hsun Sung, Mel S. Lee, Han-Tan Chai, John Y. Chiang, Yi-Chen Li, Yi-Ching Chu, Chi-Ruei Huang and Hon-Kan Yip
Biomedicines 2021, 9(10), 1362; https://doi.org/10.3390/biomedicines9101362 - 30 Sep 2021
Cited by 2 | Viewed by 1749
Abstract
This study tested whether extracorporeal shock wave (ECSW) supported-exogenous mitochondria (Mito) into adipose-derived mesenchymal stem cells (ADMSCs) would preserve left-ventricular-ejection-fraction (LVEF) in doxorubicin/12 mg/kg-induced dilated cardiomyopathy (DCM) rat. Adult-male-SD rats were equally categorized into group 1 (sham-control), group 2 (DCM), group 3 (DCM [...] Read more.
This study tested whether extracorporeal shock wave (ECSW) supported-exogenous mitochondria (Mito) into adipose-derived mesenchymal stem cells (ADMSCs) would preserve left-ventricular-ejection-fraction (LVEF) in doxorubicin/12 mg/kg-induced dilated cardiomyopathy (DCM) rat. Adult-male-SD rats were equally categorized into group 1 (sham-control), group 2 (DCM), group 3 (DCM + ECSW/1.5 mJ/mm2 for 140 shots/week × 3 times/since day 14 after DCM induction), group 4 (DCM + ECSW/1.5 mJ/mm2/100 shots-assisted mito delivery (500 μg) into ADMSCs/1.2 × 106 cells, then implanted into LV myocardium day 14 after DCM induction) and group 5 (DCM + ECSW-assisted mito delivery into ADMSCs/1.2 × 106 cells, then implanted into LV, followed by ECSW/1.5 mJ/mm2 for 140 shots/week × 3 times/since day 14 after DCM induction) and euthanized by day 49. Microscopic findings showed mitochondria were abundantly enhanced by ECSW into H9C2 cells. The q-PCR showed a significant increase in relative number of mitDNA in mitochondrial-transferred H9C2 cells than in control group (p < 0.01). The angiogenesis/angiogenesis factors (VEGF/SDF-1α/IG-F1) in HUVECs were significantly progressively increased by a stepwise-increased amount of ECSW energy (0.1/0.25/0.35 mJ/mm2) (all p < 0.001). The 49-day LVEF was highest in group 1 and significantly progressively increased from groups 2 to 5 (all p < 0.0001). Cardiomyocyte size/fibrosis exhibited an opposite pattern of LVEF, whereas cellular/protein levels of angiogenesis factors (VEGF/SDF-1α) in myocardium were significantly progressively increased from groups 1 to 5 (all p < 0.0001). The protein expressions of apoptotic/mitochondrial (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax/cytosolic-cytochrome-C), fibrotic (p-Smad3/TGF-ß), oxidative-stress (NOX-1/NOX-2) and pressure-overload/heart failure (BNP/ß-MHC) biomarkers exhibited an opposite pattern of LVEF among the five groups (all p < 0.0001). ECSW-assisted mitochondrial-delivery into ADMSCs plus ECSW offered an additional benefit for preserving LVEF in DCM rat. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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Review

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14 pages, 303 KiB  
Review
Translational Applications of Extracorporeal Shock Waves in Dental Medicine: A Literature Review
by Abdulmonem Alshihri
Biomedicines 2022, 10(4), 902; https://doi.org/10.3390/biomedicines10040902 - 14 Apr 2022
Cited by 2 | Viewed by 1965
Abstract
Extracorporeal shock wave therapy (ESWT) has been studied and applied extensively in medical practice for various applications including musculoskeletal, dermal, vascular, and cardiac indications. These indications have emerged from primary ESWT use in treating urolithiasis and cholelithiasis. Likewise, dental medicine has had its [...] Read more.
Extracorporeal shock wave therapy (ESWT) has been studied and applied extensively in medical practice for various applications including musculoskeletal, dermal, vascular, and cardiac indications. These indications have emerged from primary ESWT use in treating urolithiasis and cholelithiasis. Likewise, dental medicine has had its share of utilizing ESWT in various investigations. This review aimed to provide an up-to-date summary of ESWT use in preclinical and clinical dental medicine. There is growing interest in ESWT use stemming from its non-invasiveness, low cost, and safe qualities in addition to its proven regenerative biostimulating aspects. Targeted tissue and parameters of ESWT delivery continue to be an integral part of successful ESWT treatment to attain the clinical value of the anticipated dose’s effect. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
17 pages, 1317 KiB  
Review
New Frontiers of Extracorporeal Shock Wave Medicine in Urology from Bench to Clinical Studies
by Po-Yen Chen, Jai-Hong Cheng, Zong-Sheng Wu and Yao-Chi Chuang
Biomedicines 2022, 10(3), 675; https://doi.org/10.3390/biomedicines10030675 - 15 Mar 2022
Cited by 11 | Viewed by 3713
Abstract
A shock wave (SW), which carries energy and propagates through a medium, is a type of continuous transmitted sonic wave that can achieve rapid energy transformations. SWs have been applied for many fields of medical science in various treatment settings. In urology, high-energy [...] Read more.
A shock wave (SW), which carries energy and propagates through a medium, is a type of continuous transmitted sonic wave that can achieve rapid energy transformations. SWs have been applied for many fields of medical science in various treatment settings. In urology, high-energy extracorporeal SWs have been used to disintegrate urolithiasis for 30 years. However, at lower energy levels, SWs enhance the expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), proliferating cell nuclear antigen (PCNA), chemoattractant factors, and the recruitment of progenitor cells, and inhibit inflammatory molecules. Low energy extracorporeal shock wave (LESW) therapy has been used in urology for treating chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), interstitial cystitis/bladder pain syndrome (IC/BPS), overactive bladder, stress urinary incontinence, and erectile dysfunction through the mechanisms of anti-inflammation, neovascularization, and tissue regeneration. Additionally, LESW have been proven to temporarily increase tissue permeability and facilitate intravesical botulinum toxin delivery for treating overactive bladders in animal studies and in a human clinical trial. LESW assisted drug delivery was also suggested to have a synergistic effect in combination with cisplatin to improve the anti-cancer effect for treating urothelial cancer in an in vitro and in vivo study. LESW assisted drug delivery in uro-oncology is an interesting suggestion, but no comprehensive clinical trials have been conducted as of yet. Taken together, LESW is a promising method for the treatment of various diseases in urology. However, further investigation with a large scale of clinical studies is necessary to confirm the real role of LESW in clinical use. This article provides information on the basics of SW physics, mechanisms of action on biological systems, and new frontiers of SW medicine in urology. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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15 pages, 2952 KiB  
Review
Use of the Shock Wave Therapy in Basic Research and Clinical Applications—From Bench to Bedsite
by Piotr Rola, Adrian Włodarczak, Mateusz Barycki and Adrian Doroszko
Biomedicines 2022, 10(3), 568; https://doi.org/10.3390/biomedicines10030568 - 28 Feb 2022
Cited by 13 | Viewed by 4881
Abstract
Shock Waves (SW) are acoustic disturbances that propagate through a medium carrying the energy. These specific sonic pulses are composed of two phases—high positive pressure, a rise time < 10 ns, and a tensile wave. Originally Shock Waves were introduced to clinical practice [...] Read more.
Shock Waves (SW) are acoustic disturbances that propagate through a medium carrying the energy. These specific sonic pulses are composed of two phases—high positive pressure, a rise time < 10 ns, and a tensile wave. Originally Shock Waves were introduced to clinical practice as a part of the lithotripsy therapy focused on disrupting calcific deposits in the body. Since that time, shock wave therapy (SWT) has gone far beyond the original application related to the destruction of kidney stones. In this narrative Review, we present basic clinical applications of the SWT along with the potential therapeutic application in clinical practice. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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17 pages, 1431 KiB  
Review
Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment
by Yuan-Hong Jiang, Jia-Fong Jhang, Yu-Khun Lee and Hann-Chorng Kuo
Biomedicines 2022, 10(2), 396; https://doi.org/10.3390/biomedicines10020396 - 07 Feb 2022
Cited by 11 | Viewed by 2888
Abstract
Low-energy shock wave (LESW) therapy is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated to be effective in treating chronic prostatitis and pelvic pain syndrome as well as overactive bladder, and it has a potential effect [...] Read more.
Low-energy shock wave (LESW) therapy is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated to be effective in treating chronic prostatitis and pelvic pain syndrome as well as overactive bladder, and it has a potential effect on interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. LESW reduces pain behavior, downregulates nerve growth factor expression, and suppresses bladder overactivity by decreasing the expression of inflammatory proteins. Previous rat IC models have shown that LESW can increase urothelial permeability, facilitate intravesical delivery of botulinum toxin A (BoNT-A), and block acetic acid-induced hyperactive bladder, suggesting that LESW might be a potential therapeutic module for relieving bladder inflammatory conditions, such as bladder oversensitivity, IC/BPS, and overactive bladder. A recent clinical trial showed that LESW monotherapy was associated with a significant reduction in pain scores and IC symptoms. BoNT-A detrusor injection or liposome-encapsulated BoNT-A instillation could also inhibit inflammation and improve IC symptoms. However, BoNT-A injection requires anesthesia and certain complications might occur. Our preliminary study using LESW plus intravesical BoNT-A instillation every week demonstrated an improvement in global response assessment without any adverse events. Moreover, an immunohistochemistry study revealed the presence of cleaved SNAP25 protein in the suburothelium of IC bladder tissue, indicating that BoNT-A could penetrate across the urothelial barrier after application of LESW. These results provide evidence for the efficacy and safety of this novel IC/BPS treatment by LESW plus BoNT-A instillation, without anesthesia, and no bladder injection. This article reviews the current evidence on LESW and LESW plus intravesical therapeutic agents on bladder disorders and the pathophysiology and pharmacological mechanism of this novel, minimally invasive treatment model for IC/BPS. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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Other

Jump to: Research, Review

31 pages, 719 KiB  
Systematic Review
The Effects of the Exposure of Musculoskeletal Tissue to Extracorporeal Shock Waves
by Tobias Wuerfel, Christoph Schmitz and Leon L. J. Jokinen
Biomedicines 2022, 10(5), 1084; https://doi.org/10.3390/biomedicines10051084 - 06 May 2022
Cited by 11 | Viewed by 4873
Abstract
Extracorporeal shock wave therapy (ESWT) is a safe and effective treatment option for various pathologies of the musculoskeletal system. Many studies address the molecular and cellular mechanisms of action of ESWT. However, to date, no uniform concept could be established on this matter. [...] Read more.
Extracorporeal shock wave therapy (ESWT) is a safe and effective treatment option for various pathologies of the musculoskeletal system. Many studies address the molecular and cellular mechanisms of action of ESWT. However, to date, no uniform concept could be established on this matter. In the present study, we perform a systematic review of the effects of exposure of musculoskeletal tissue to extracorporeal shock waves (ESWs) reported in the literature. The key results are as follows: (i) compared to the effects of many other forms of therapy, the clinical benefit of ESWT does not appear to be based on a single mechanism; (ii) different tissues respond to the same mechanical stimulus in different ways; (iii) just because a mechanism of action of ESWT is described in a study does not automatically mean that this mechanism is relevant to the observed clinical effect; (iv) focused ESWs and radial ESWs seem to act in a similar way; and (v) even the most sophisticated research into the effects of exposure of musculoskeletal tissue to ESWs cannot substitute clinical research in order to determine the optimum intensity, treatment frequency and localization of ESWT. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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20 pages, 2713 KiB  
Systematic Review
Relative Effect of Extracorporeal Shockwave Therapy Alone or in Combination with Noninjective Treatments on Pain and Physical Function in Knee Osteoarthritis: A Network Meta-Analysis of Randomized Controlled Trials
by Chun-De Liao, Yu-Yun Huang, Hung-Chou Chen, Tsan-Hon Liou, Che-Li Lin and Shih-Wei Huang
Biomedicines 2022, 10(2), 306; https://doi.org/10.3390/biomedicines10020306 - 28 Jan 2022
Cited by 4 | Viewed by 3359
Abstract
Extracorporeal shockwave therapy (ESWT) has been recommended for managing pain in patients with knee osteoarthritis (KOA). The difference in therapeutic effects between radial shockwave characteristics (RaSW) and focused shockwave characteristics (FoSW) with different energy levels for KOA remains controversial. The purpose of this [...] Read more.
Extracorporeal shockwave therapy (ESWT) has been recommended for managing pain in patients with knee osteoarthritis (KOA). The difference in therapeutic effects between radial shockwave characteristics (RaSW) and focused shockwave characteristics (FoSW) with different energy levels for KOA remains controversial. The purpose of this network meta-analysis (NMA) was to identify the effects relative to the different ESWT regime and combination treatments on pain and functional outcomes in individuals with KOA. The randomized controlled trials (RCTs) which investigated the efficacy of RaSW, FoSW, and combination treatments in patients with KOA were identified by searches of electronic databases. The included RCTs were analyzed through NMA and risk-of-bias assessment. We analyzed 69 RCTs with a total of 21 treatment arms in the NMA. Medium-energy FoSW plus physical therapy, medium-energy acupoint RaSW plus Chinese medicine, and high-energy FoSW alone were the most effective treatments for reducing pain [standard mean difference (SMD) = −4.51], restoring function (SMD = 4.97), and decreasing joint inflammation (SMD = −5.01). Population area and study quality influenced the treatment outcomes, particularly pain. Our findings indicate that medium-energy ESWT combined with physical therapy or Chinese medicine is beneficial for treating pain and increasing function in adults with KOA. Full article
(This article belongs to the Special Issue Translational Research in Shock Wave Medicine)
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