Scientific Support

Extracorporeal Shockwaves

High- and low energy shockwaves have been proven to work as a useful treatment in many different diseases. The underlying mechanism responsible for the broad variety of processes initiated (e.g. genexpression TGF-beta 1, neovascularization, anti-inflammatory response, up-regulation of PCNA), is known as cellular mechanical transduction. It is described as the ability to receive or rather forward mechanical input and to produce a biological answer. Not only over 80% of our cell parts are sensitive to mechanical stress but it has been shown, that physical input is able to activate our cells through mechanical transduction

“SW are able to relief pain, as well to positively regulate inflammation, 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.”

Link to source: https://pubmed.ncbi.nlm.nih.gov/26612525/

d’Agostino, M. C.; Craig, K.; Tibalt, E.; Respizzi, S. (2015): Shock wave as biological therapeutic tool: From mechanical stimulation to recovery and healing, through mechanotransduction. In: International journal of surgery (London, England) 24 (Pt B),147-53. doi: 10.1016/j.ijsu.2015.11.030.

Relieves pain, broadens range of motion and strengthens muscles in treatment of shoulder calcific tendinitis.

Link to source: https://europepmc.org/article/med/19358394

Avancini-Dobrovic, V., Frlan-Vrgoc, L., Stamenkovic, D., Pavlovic, I. & Vrbanic, T.S. (2011). Radial Extracorporeal Shockwave Therapy in the Treatment of Shoulder Calcific Tendinitis. Coll Antropol; 35(2)221-5.0.

“The success rate for treatment of tendinopathies, such as tennis elbow, periarthritis humeroscapularis or calcaneal spur, was approximately 80%. For calcific tendinitis shock wave therapy seems to be superior to all other minimal or noninvasive techniques without compromising a potential later operation.”

Link to source: https://pubmed.ncbi.nlm.nih.gov/9186313/

Haupt, G. (1997). Use of Extracorporeal Shock Waves in the Treatment of Pseudoarthrosis, Tendinopathy and Ohter Orthopedic Diseases. The Journal of UrologyM 158(1),4-11.

“Improves spasticity and motor functionality. ESWT might efficiently improve spasticity in affected children and also their gross motor functionality.”

Link to source: https://pubmed.ncbi.nlm.nih.gov/23603803/

Ilieva, E., Gonkova, M. & Chavdarov, I. (2011). Effect of Shock Wave Therapy on Muscle Spasticity in Children with Cerebral Palsy. Annals of Physical and Rehabilitation Medicine; 54(1).

“There is growing evidence that both, radial as well as focused ESWT and the combination of both are able to improve the degree of cellulite.”

Link to source: https://pubmed.ncbi.nlm.nih.gov/26209782/

Knobloch, K. & Kraemer, R. (2015). Extracorporeal shock wave therapy (ESWT) for the treatment of cellulite – A current metaanalysis. Int J Surg;24,210-7. doi:10.1016/j.ijsu.2015.07.644.

“Fibroblasts play a crucial role in wound healing and the healthy structure of the dermal connective tissue. They synthesize structureal proteins and components of the extracellular matrix. The fibroblast activity determines the appearance of the skin through the structure of the tissue, the promotion of migration and adhesion of cells and the regulation of the moisture balance. These observations contribute  to a tightening of the skin, which could be proven in-vivo. In particular, the combined use of hyaluronic acid and shock waves was ablte to reduce wrinkles and roughness in the periorbital and glabellar region over a period of three months.”

Link to source: https://ediss.sub.uni-hamburg.de/volltexte/2012/5682/pdf/Dissertation.pdf

Neumann, K.B. (2012). Untersuchung der Wirkung Extrakorporaler Stoßwellentherapie auf die Haut. Effekte der Mechanotransduktion auf Fibroblasten invitro und Analyse von Hautveränderungen in-vivo (Dissertation). Universität Hamburg, Hamburg.

“Therefore it seemed likely that physical shockwaves raise the machnotransduction and convert into biological signals that lead to a cascade of biological responses in tendons.”

Link to source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666498/

Notarnicola, A. & Moretti, B. (2012). The biological effects of extracorporal shock wave therapy (eswt) on tendon tissue. Muscles, ligaments and Tendons Journal,2(1):33-7.

“Extracorporeal shockwave treatment was shown to improve orthopaedic diseases and wound healing and to stimulate lymphangiogenesis in vivo. Our findings help to understand the cellular and molecular mechanisms underlying shockwave-induced lymphangiogenesis in vivo.”

Link to source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114806

Rohringer, S., Holnthoner, W., Hackl, M., Weihs, A. M., Rünzler, D. et al., (2014). Molecular and Cellular Effects of In Vitro Shockwave Treatment on Lymphatic Endothelial Cells.PLoS ONE 9(12).

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Mechanical Transduction

“Note that there are many excellent reviews in the literature that focus on different types of cells, including cardiac fibroblasts (MacKenna et al., 2000), cardiac myocytes (Sadoshima and Izumo, 1997), smooth muscle cells (Osol, 1995), endothelial cells (Davies, 1995; Resnick and Gimbrone, 1995), bone cells (Duncan and Turner, 1995), lung cells (Liu and Post, 2000), and dermal fibroblasts (Silver et al., 2003a). Interested readers should consult these references for an in-depth understanding of the topic of cellular mechanotransduction mechanisms.” (Wang, 2006, p.1573)

“As an example, neurotransmitter release from motor nerve terminals can be detected within 10–20 msec after cell surface integrins are mechanically stressed.”

Link to source: https://science.sciencemag.org/content/269/5230/1578

Chen, B.M. & Grinnell, A.D. (1995). Integrins and modulation of transmitter release from motor nerve terminals by stretch. Science 269:1578–1580, pmid:7667637.

Mechanical Transduction can influence essential cell functions like migration, proliferation, differentiation and apoptosis. Additionally it can higher the sensitivity of cells through mechanical preload.

Link to source: https://pubmed.ncbi.nlm.nih.gov/26612525/

d’Agostino, M. C., Craig, K., Tibalt, E. & Respizzi, S. (2015): Shock wave as biological therapeutic tool: From mechanical stimulation to recovery and healing, through mechanotransduction. In: International journal of surgery (London, England) 24 (Pt B), S. 147–153. DOI: 10.1016/j.ijsu.2015.11.030.

“Cells react to tensile forces of the extracellular matrix. Those forces may influence intracellular mechanisms like gene expression or the movement speed of cells.”

Link to source: https://pubmed.ncbi.nlm.nih.gov/25355505/

Humphrey, J.D., Dufresne, E.R. & Schwartz, M.A. (2014). Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol;15(12):802-812. doi:10.1038/nrm3896

Mechanical signals may be integrated with other environmental signals and transduced into a biochemical response through force-dependent changes in scaffold geometry or molecular mechanics.

Link to source: https://www.annualreviews.org/doi/abs/10.1146/annurev.physiol.59.1.575

Ingber, D. E. (1997). Tensegrity: the architectural basis of cellular mechanotransduction. Annu. Rev. Physiol., 59(1), 575–599. https://doi.org/10.1146/annurev.physiol.59.1.575

A majority of cell parameters are sensitive to mechanical stress. Molecular mechanisms of mechanical transduction are: higher cell activity, modification of catalytic activity of enzymes, alter biochemical activities through an influence of the elastic properties of peptides, higher chemical potential of proteins; „it should be clear from the discussion that cellular mechnotransduction cannot be understood in isolation or defined entirely in terms of mechanosensitive molecules. […] The cellular response will be governed by how mechanical forces are distributed throughout the organ and tissue of which it is a part, as well as by the level of preexisting tension in the ECM.“

Link to source: https://pubmed.ncbi.nlm.nih.gov/16675838/

Ingber, D. E. (2006). Cellular mechanotransduction: putting all the pieces together again. The FASEB Journal,20,811-27.

“Consequently, defects in mechanotransduction–often caused by mutations or misregulation of proteins that disturb cellular or extracellular mechanics–are implicated in the development of a wide array of diseases, ranging from muscular dystrophies and cardiomyopathies to cancer progression and metastasis.” Jaalouk & Lammerding furthermore provide detailed information about the biological components of mechanical transduction.

Link to source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668954/pdf/nihms98005.pdf

Jaalouk, D. E., &Lammerding, J. (2009). Mechanotransduction gone awry. Nature Reviews Molecular Cell Biology10,63-73 (Januar 2009).

“In conclusion, on the basis of our data and the proposed model, we suggest that connective tissue cells can coordinate their responses to mechanical forces through adherens junctions. These junctions mediate the activation of stretch-activated ion channels and subsequently facilitate the reorganization of actin filaments.”

Link to source: https:://www.jbc.org/contenct/276/38/35967.pdf

Ko, K.S., Arora, P.D. & McCullock, C.A. (2001). Cadherins mediate intercellular mechanical signaling in fibroblasts by activation of stretch-sensitive calcium-permeable channels. The Journal of Biological Chemistry, 276, 35967-77.

“During mechanotransduction, force allosterically alters the functions of mechanosensitive proteins within adhesions to elicit biochemical signals that regulate both rapid responses in cellular mechanics and long-term changes in gene expression. Integrin-mediated mechanotransduction plays important roles in development and tissue homeostasis, and its dysregulation is often associated with diseases.”

Link to source: https://pubmed.ncbi.nlm.nih.gov/27872252/

Sun, Z., Guo, S.S. & Fässler, R. (2016). Integrin-mediated mechanotransduction. J Cell Biol;215(4):445-456. doi:10.1083/jcb.201609037

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Low energy shockwaves (evocell)​

“Low energy level shockwaves with low impulses showed positive stimulatory effects, whereas the high energy level with high impulses had significant inhibitory effects. At lower energy, up-regulation of proliferating cell nuclear antigen (PCNA), collagen type 1 & 3 and TGF-beta 1 gene expression were observed, followed by an increase in NO [nitric oxide, ed. note] production, TGFb1 and collagen synthesis.” (Orhan et al., 2004)

In vivo studies and have demonstrated that extracorporeal cardiac shock wave therapy with a low-energy SW upregulates the expression of VEGF, induces neovascularization, and improves myocardial ischemia in a porcine model of chronic myocardial ischemia without any adverse effects in vivo.

Link to source: https://www.jstage.jst.go.jp/article/tjem/219/1/219_1_1/_article

Ito, K. & Fukumoto, Y., Shimokawa, H. (2009). Extracorporeal Shock Wave Therapy as a New and Non-invasive Angiogenic Strategy. The Tohoku journal of experimental medicine. 219. 1-9. 10.1620/tjem.219.1.

“Tenocytes at the hypertrophied cellular tissue and newly developed tendon tissue expressed strong proliferating cell nuclear antigen (PCNA) after ESW treatment, suggesting that physical ESW could increase the mitogenic responses of tendons.

Low‐energy shock wave effectively promoted tendon healing. TGF‐β1 and IGF‐I played important roles in mediating ESW‐stimulated cell proliferation and tissue regeneration of tendon.”

Link to source: https://onlinelibrary.wiley.com/doi/10.1016/j.orthres.2003.10.013

Chen, Y.-J., Wang, C.-J., Yang, K. D., Kuo, Y.-R., Huang, H.-C., Huang, Y.-T. et al. (2004). Extracorporeal shock waves promote healing of collagenase-induced Achilles tendinitis and increase TGF-beta1 and IGF-I expression. Journal of Orthopaedic Research: official publication of the Orthopaedic Research Society, 22 (4), 854-861. doi: 10.1016/j.orthres.2003.10.013.

A significant enhancement in normal or delayed healing was found with low-dose treatment (10 SW at 14 kV). The stimulating effect of low-energy shock waves coincides with significantly increased vascularization of the upper dermis and thicker layer of the newly formed epithelial cells covering the wound.

Link to source: https://europepmc.org/article/med/2359293

Haupt, G., & Chvapil, M. (1990). Effect of shock waves on the healing of partialthickness wounds in piglets. Journal of Surgical Research, 49(1), 45-8. https://doi.org/10.1016/0022-4804(90)90109-f.

“Low-energy shockwaves suppressed adipocyte differentiation by decreasing PPARγ. Our study suggests an insight into potential uses of shockwave-treatment for obesity.”

Link to source: https://www.mdpi.com/2073-4409/9/1/166/pdf

Cho, W.; Kim, S.; Jeong, M.; Park, Y.M. Shockwaves Suppress Adipocyte Differentiation via Decrease in PPARγ. Cells 2020, 9, 166.

“There was a significant alleviation of pain and improvement of function at all follow-ups in the treatment group.”

Link to source: https://link.springer.com/article/10.1007/BF00573445

Rompe, J.D., Hopf, C., Nafe, B., & Bürger, R. (1996). Low-energy extracorporeal shock wave therapy for painful heel: a prospective controlled single-blind study. Archives of Orthopaedic and Trauma Surgery; 115(2),75-9.

“These data demonstrate that brief exposure to extremely low-amplitude mechanical strains can enhance the biologic fixation of cementless implants. Moreover, the degree of ingrowth is dependent on the frequency of the applied strain.”

Link to source: https://europepmc.org/article/med/8118971

Rubin, C. T. & McLeod, K. J., (1984). Promotion of bony ingrowth by frequency-specific, low-amplitude mechanical strain. ClinOrthopRelat Res,298,165-74.

“Low intensity extracorporeal shock wave therapy has a positive short-term clinical and physiological effect on the erectile function of men who respond to oral phosphodiesterase type 5 inhibitor therapy.

Link to source: https://pubmed.ncbi.nlm.nih.gov/22425129/

Vardi, Y., Appel, B., Kilchevsky, A. & Gruenwald, I. (2012). Does Low Intensity Extracorporeal Shock Wave Therapy Have a Physiological Effect on Erectile Function? Short-Term Results of a Randomized, Double-Blind, Sham Controlled Study. The Journal of Urology;187(5);1769-75.

“We found cortical bone adaptation to mechanical loading to increase with increasing loading frequency up to 5-10 Hz and to plateau with frequencies beyond 10 Hz.”

Link to source: https://pubmed.ncbi.nlm.nih.gov/14962804/

Warden, S. J. & Turner, C. H., (2004). Mechanotransduction in cortical bone is most efficient at loading frequencies of 5-10 Hz. Bone,34,261-70.

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