EXTRACORPOREAL SHOCK WAVE THERAPY FOR SOFT TISSUE INJURIES AND WOUNDS: PATHOPHYSIOLOGY, MECHANISMS OF ACTION AND EFFICACY
DOI:
https://doi.org/10.32782/pub.health.2026.1.25Keywords:
soft tissue injuries and wounds, extracorporeal shock wave therapy, pathophysiology, mechanisms of action, effectivenessAbstract
Topicality. The combination of analysis of the pathophysiology of ballistic injuries and modern therapeutic approaches, in particular shock wave therapy (SWT), allows us to evaluate promising strategies for improving treatment outcomes and developing effective methods for patient recovery.
Purpose of the work. Analysis of modern views on the pathophysiology, mechanisms of action and efficacy of extracorporeal shock wave therapy for soft tissue injuries and wounds.
Materials and methods. The research that forms the basis of this article is based on a systematic analysis of published scientific literature on the problem of pathophysiology, mechanisms of action and efficacy of extracorporeal shock wave therapy for soft tissue injuries and wounds.
Research results. The higher clinical efficacy of UHT in the treatment of acute and chronic soft tissue wounds compared to monotherapy with traditional methods is substantiated. The need for further high-quality randomized studies is emphasized to more accurately determine its role and optimal application parameters. The prospects for developing complex therapeutic strategies that combine the natural regenerative potential of tissues with modern medical interventions are shown, including UHT as a non-invasive method of stimulating recovery. Attention is focused on early interventions aimed at activating satellite cells, inhibiting catabolic processes, and stimulating angiogenesis - effects that are partially realized under the influence of shock wave therapy. The use of tissue-engineered bioconstructs for restoring muscle mass in severe injuries, as well as the introduction of a multidisciplinary approach to treatment, is recognized as additionally promising.
Conclusions. It is necessary to conduct research aimed at optimizing rehabilitation programs, in particular, determining effective combinations of physical activity, nutritional support, and pharmacotherapy in combination with UHT to achieve the most complete functional recovery.
References
Moriscot A., Miyabara E. H., Langeani B., Belli A., Egginton S., Bowen T. S. Firearms-related skeletal muscle trauma: pathophysiology and novel approaches for regeneration. npj Regenerative Medicine. 2021. Vol. 17. P. 1–17. https://doi.org/10.1038/s41536-021-00127-1
Spear A. M., Lawton G., Staruch R. M. T., Rickard R. F. Regenerative medicine and war: a front-line focus for UK defence. NPJ Regenerative Medicine. 2018. Vol. 3. Art. 13. https://doi.org/10.1038/s41536-018-0053-4
Belmont P. J. Jr., McCriskin B. J., Sieg R. N., Burks R., Schoenfeld A. J. Combat wounds in Iraq and Afghanistan from 2005 to 2009. Journal of Trauma and Acute Care Surgery. 2012. Vol. 73. P. 3–12.https://doi.org/10.1097/TA.0b013e318250bfb4.
Davies M., Kerins M., Glucksman E. Inner-city gunshot wounds: 10 years on. Injury. 2011. Vol. 42. P. 488–491. https://doi.org/10.1016/j.injury.2010.09.041.
Bartlett C. S., Helfet D. L., Hausman M. R., Strauss E. Ballistics and gunshot wounds: effects on musculoskeletal tissues. Journal of the American Academy of Orthopaedic Surgeons. 2000. Vol. 8. P. 21–36. https://doi.org/10.5435/00124635-200001000-00003.
Stefanopoulos P. K. et al. Wound ballistics of military rifle bullets: an update on controversial issues and associated misconceptions. Journal of Trauma and Acute Care Surgery. 2019. Vol. 87. P. 690–698. https://doi.org/10.1097/TA.0000000000002290.
Lendrum R. A., Lockey D. Trauma system development. Anaesthesia. 2013. Vol. 68. P. 30–39.https://doi.org/10.1111/anae.12049.
Lale A., Krajewski A., Friedman L. S. Undertriage of firearm-related injuries in a major metropolitan area. JAMA Surgery. 2017. Vol. 152. P. 467–474. https://doi.org/10.1001/jamasurg.2016.5049.
Mauro A. Satellite cell of skeletal muscle fibers. Journal of Biophysical and Biochemical Cytology. 1961. Vol. 9. P. 493–495. https://doi.org/10.1083/jcb.9.2.493.
Yin H., Price F., Rudnicki M. A. Satellite cells and the muscle stem cell niche. Physiological Reviews. 2013. Vol. 93. P. 23–67. https://doi.org/10.1152/physrev.00043.2011.
Baghdadi M. B., Tajbakhsh S. Regulation and phylogeny of skeletal muscle regeneration. Developmental Biology. 2018. Vol. 433. P. 200–209. https://doi.org/10.1016/j.ydbio.2017.07.026.
Schmidt M., Schuler S. C., Huttner S. S., von Eyss B., von Maltzahn J. Adult stem cells at work: regenerating skeletal muscle. Cellular and Molecular Life Sciences. 2019. Vol. 76. P. 2559–2570. https://doi.org/10.1007/s00018-019-03093-6.
Tidball J. G. Inflammatory cell response to acute muscle injury. Medicine and Science in Sports and Exercise. 1995. Vol. 27. P. 1022–1032. https://doi.org/10.1249/00005768-199507000-00011.
Bentzinger C. F., Wang Y. X., Dumont N. A., Rudnicki M. A. Cellular dynamics in the muscle satellite cell niche. EMBO Reports. 2013. Vol. 14. P. 1062–1072. https://doi.org/ 10.1038/embor.2013.182.
Dort J., Fabre P., Molina T., Dumont N. A. Macrophages are key regulators of stem cells during skeletal muscle regeneration and diseases. Stem Cells International. 2019. Art. 4761427. https://doi.org/ 10.1155/2019/4761427
Relaix F., Zammit P. S. Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage. Development. 2012. Vol. 139. P. 2845–2856.https://doi.org/10.1242/dev.069088.
Hardy D. et al. Comparative study of injury models for studying muscle regeneration in mice. PLoS ONE. 2016. Vol. 11. Art. e0147198. https://doi.org/10.1371/journal.pone.0147198
Stilhano R. S. et al. Reduction in skeletal muscle fibrosis of spontaneously hypertensive rats after laceration by microRNA targeting angiotensin II receptor. PLoS ONE. 2017. Vol. 12. Art. e0186719.https://doi.org/10.1371/journal.pone.0186719.
Miyabara E. H. et al. Mammalian target of rapamycin complex 1 is involved in differentiation of regenerating myofibers in vivo. Muscle & Nerve. 2010. Vol. 42. P. 778–787.https://doi.org/10.1002/mus.21754.
Feige P., Brun C. E., Ritso M., Rudnicki M. A. Orienting muscle stem cells for regeneration in homeostasis, aging, and disease. Cell Stem Cell. 2018. Vol. 23. P. 653–664.https://doi.org/10.1016/j.stem.2018.10.006.
Evano B., Tajbakhsh S. Skeletal muscle stem cells in comfort and stress. npj Regenerative Medicine. 2018. Vol. 3. Art. 24. https://doi.org/10.1038/s41536-018-0062-3
Fuchs E., Blau H. M. Tissue stem cells: architects of their niches. Cell Stem Cell. 2020. Vol. 27. P. 532–556.https://doi.org/10.1016/j.stem.2020.09.011.
Forcina L., Cosentino M., Musaro A. Mechanisms regulating muscle regeneration: insights into the interrelated and time-dependent phases of tissue healing. Cells. 2020. Vol. 9. https://doi.org/10.3390/cells9051297
Sicherer S. T., Venkatarama R. S., Grasman J. M. Recent trends in injury models to study skeletal muscle regeneration and repair. Bioengineering (Basel). 2020. Vol. 7. https://doi.org/10.3390/bioengineering7030076
Carnes M. E., Pins G. D. Skeletal muscle tissue engineering: biomaterials-based strategies for the treatment of volumetric muscle loss. Bioengineering (Basel). 2020. Vol. 7. DOI: https://doi.org/10.3390/bioengineering7030085
Grogan B. F., Hsu J. R., Skeletal Trauma Research Consortium. Volumetric muscle loss. Journal of the American Academy of Orthopaedic Surgeons. 2011. Vol. 19. P. S35–S37.https://doi.org/10.5435/00124635-201102001-00007.
Greising S. M. et al. Unwavering pathobiology of volumetric muscle loss injury. Scientific Reports. 2017. Vol. 7. Art. 13179. https://doi.org/10.1038/s41598-017-13306-2
Aguilar C. A. et al. Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury. Cell Death Discovery. 2018. Vol. 4. Art. 33. https://doi.org/10.1038/s41420-018-0027-8
Matecki S. et al. Leaky ryanodine receptors contribute to diaphragmatic weakness during mechanical ventilation. Proceedings of the National Academy of Sciences of the USA. 2016. Vol. 113. P. 9069–9074.https://doi.org/10.1073/pnas.1609707113.
Schiaffino S., Dyar K. A., Ciciliot S., Blaauw B., Sandri M. Mechanisms regulating skeletal muscle growth and atrophy. FEBS Journal. 2013. Vol. 280. P. 4294–4314.https://doi.org/10.1111/febs.12253.
Evans K. N. et al. Inflammatory cytokine and chemokine expression is associated with heterotopic ossification in high-energy penetrating war injuries. Journal of Orthopaedic Trauma. 2012. Vol. 26. P. e204–e213. https://doi.org/10.1097/BOT.0b013e31825d60a5
Friedrich O. et al. The sick and the weak: neuropathies/myopathies in the critically ill. Physiological Reviews. 2015. Vol. 95. P. 1025–1109.https://doi.org/10.1152/physrev.00028.2014.
Siriett V. et al. Antagonism of myostatin enhances muscle regeneration during sarcopenia. Molecular Therapy. 2007. Vol. 15. P. 1463–1470.https://doi.org/10.1038/sj.mt.6300182.
Crossland H., Skirrow S., Puthucheary Z. A., Constantin-Teodosiu D., Greenhaff P. L. The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end-points. Journal of Physiology. 2019. Vol. 597. P. 1259–1270.https://doi.org/10.1113/JP275444.
Powers S. K., Morton A. B., Ahn B., Smuder A. J. Redox control of skeletal muscle atrophy. Free Radical Biology and Medicine. 2016. Vol. 98. P. 208–217.https://doi.org/10.1016/j.freeradbiomed.2016.02.021.
Dridi H. et al. Mitochondrial oxidative stress induces leaky ryanodine receptor during mechanical ventilation. Free Radical Biology and Medicine. 2020. Vol. 146. P. 383–391.https://doi.org/10.1016/j.freeradbiomed.2019.11.019.
Ottenheijm C. A., Heunks L. M., Geraedts M. C., Dekhuijzen P. N. Hypoxia induced skeletal muscle fiber dysfunction: role for reactive nitrogen species. American Journal of Physiology. Lung Cellular and Molecular Physiology. 2006. Vol. 290. P. L127–L135.https://doi.org/10.1152/ajplung.00073.2005.
Lord J. M. et al. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet. 2014. Vol. 384. P. 1455–1465.https://doi.org/10.1016/S0140-6736(14)60687-5.
Olfert I. M., Baum O., Hellsten Y., Egginton S. Advances and challenges in skeletal muscle angiogenesis. American Journal of Physiology. Heart and Circulatory Physiology. 2016. Vol. 310. P. H326–H336.https://doi.org/10.1152/ajpheart.00635.2015.
Moens S., Goveia J., Stapor P. C., Cantelmo A. R., Carmeliet P. The multifaceted activity of VEGF in angiogenesis: implications for therapy responses. Cytokine & Growth Factor Reviews. 2014. Vol. 25. P. 473–482.https://doi.org/10.1016/j.cytogfr.2014.07.009.
Li T., Kang G., Wang T., Huang H. Tumor angiogenesis and anti-angiogenic gene therapy for cancer. Oncology Letters. 2018. Vol. 16. P. 687–702. https://doi.org/ 10.3892/ol.2018.8733
Hoier B. et al. Pro- and anti-angiogenic factors in human skeletal muscle in response to acute exercise and training. Journal of Physiology. 2012. Vol. 590. P. 595–606.https://doi.org/10.1113/jphysiol.2011.216135.
Aurora A., Garg K., Corona B. T., Walters T. J. Physical rehabilitation improves muscle function following volumetric muscle loss injury. BMC Sports Science, Medicine and Rehabilitation. 2014. Vol. 6. Art. 41.https://doi.org/10.1186/2052-1847-6-41.
Quarta M. et al. Bioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss. Nature Communications. 2017. Vol. 8. Art. 15613.https://doi.org/10.1038/ncomms15613.
Tawfik V. L. et al. Angiotensin receptor blockade mimics the effect of exercise on recovery after orthopaedic trauma by decreasing pain and improving muscle regeneration. Journal of Physiology. 2020. Vol. 598. P. 317–329.https://doi.org/10.1113/JP278991.
Wuerfel T., Schmitz C., Jokinen L. L. J. The effects of the exposure of musculoskeletal tissue to extracorporeal shock waves. Biomedicines. 2022. Vol. 10. 1084. https://doi.org/10.3390/biomedicines10051084.https://doi.org/10.3390/biomedicines10051084.
Reilly J. M., Bluman E., Tenforde A. S. Effect of shockwave treatment for management of upper and lower extremity musculoskeletal conditions: a narrative review. PM&R. 2018. Vol. 10. P. 1385–1403.https://doi.org/10.1016/j.pmrj.2018.05.007.
Alshihri A., Niu W., Kammerer P. W. et al. The effects of shock wave stimulation of mesenchymal stem cells on proliferation, migration, and differentiation in an injectable gelatin matrix for osteogenic regeneration. Journal of Tissue Engineering and Regenerative Medicine. 2020. Vol. 14. P. 1630–1640.https://doi.org/10.1002/term.3126.
Leone L., Raffa S., Vetrano M. et al. Extracorporeal shock wave treatment (ESWT) enhances the in vitro-induced differentiation of human tendon-derived stem/progenitor cells (hTSPCs). Oncotarget. 2016. Vol. 7. P. 6410–6423.https://doi.org/10.18632/oncotarget.7064.
Schmitz C., Csaszar N. B., Milz S. et al. Efficacy and safety of extracorporeal shock wave therapy for orthopedic conditions: a systematic review on studies listed in the PEDro database. British Medical Bulletin. 2015. Vol. 116. P. 115–138.https://doi.org/10.1093/bmb/ldv047.
Van der Worp H., Van den Akker-Scheek I., Van Schie H., Zwerver J. ESWT for tendinopathy: technology and clinical implications. Knee Surgery, Sports Traumatology, Arthroscopy. 2013. Vol. 21. P. 1451–1458.https://doi.org/10.1007/s00167-012-2009-3.
Csaszar N. B., Angstman N. B., Milz S. et al. Radial shock wave devices generate cavitation. PLoS ONE. 2015. Vol. 10. e0140541. https://doi.org/10.1371/journal.pone.0140541
Vidal X., Marti-Fabregas J., Canet O. et al. Efficacy of radial extracorporeal shock wave therapy compared with botulinum toxin type A injection in treatment of lower extremity spasticity in subjects with cerebral palsy: a randomized controlled cross-over study. Journal of Rehabilitation Medicine. 2020. Vol. 52. e00076.https://doi.org/10.2340/16501977-2703.
Hausdorf J., Lemmens M. A., Heck K. D. et al. Selective loss of unmyelinated nerve fibers after extracorporeal shockwave application to the musculoskeletal system. Neuroscience. 2008. Vol. 155. P. 138–144.https://doi.org/10.1016/j.neuroscience.2008.03.062.
Bolt D. M., Burba D. J., Hubert J. D. et al. Determination of functional and morphologic changes in palmar digital nerves after nonfocused extracorporeal shock wave treatment in horses. American Journal of Veterinary Research. 2004. Vol. 65. P. 1714–1718.https://doi.org/10.2460/ajvr.2004.65.1714.
Takahashi N., Ohtori S., Saisu T. et al. Second application of low-energy shock waves has a cumulative effect on free nerve endings. Clinical Orthopaedics and Related Research. 2006. No. 443. P. 315–319.https://doi.org/10.1097/01.blo.0000188064.56091.a7.
Morgan J. P. M., Hamm M., Schmitz C., Brem M. H. Return to play after treating acute muscle injuries in elite football players with radial extracorporeal shock wave therapy. Journal of Orthopaedic Surgery and Research. 2021. Vol. 16. 708.https://doi.org/10.1186/s13018-021-02853-0.
Melzack R., Wall P. D. Pain mechanisms: a new theory. Science. 1965. Vol. 150. P. 971–979.https://doi.org/10.1126/science.150.3699.971.
Suputtitada A., Chen C. P. C., Ngamrungsiri N., Schmitz C. Effects of repeated injection of 1% lidocaine vs. radial extracorporeal shock wave therapy for treating myofascial trigger points: a randomized controlled trial. Medicina. 2022. Vol. 58. 479.https://doi.org/10.3390/medicina58040479.
Goats G. C. Massage – the scientific basis of an ancient art: Part 2. Physiological and therapeutic effects. British Journal of Sports Medicine. 1994. Vol. 28. P. 153–156. https://doi.org/ 10.1136/bjsm.28.3.153
Kohrs R. T., Zhao C., Sun Y. L. et al. Tendon fascicle gliding in wild type, heterozygous, and lubricin knockout mice. Journal of Orthopaedic Research. 2011. Vol. 29. P. 384–389.https://doi.org/10.1002/jor.21247.
Willkomm L. M., Bickert B., Wendt H. et al. Weiterbehandlung und Rehabilitation nach Beugesehnenverletzungen (postoperative treatment and rehabilitation following flexor tendon injuries). Unfallchirurg. 2020. Vol. 123. P. 126–133.https://doi.org/10.1007/s00113-019-00758-6.
Pavan P. G., Stecco A., Stern R., Stecco C. Painful connections: densification versus fibrosis of fascia. Current Pain and Headache Reports. 2014. Vol. 18. 441.https://doi.org/10.1007/s11916-014-0441-4.
Zhang L., Fu X. B., Chen S. et al. Efficacy and safety of extracorporeal shock wave therapy for acute and chronic soft tissue wounds: a systematic review and meta-analysis. International Wound Journal. 2018. Vol. 15. P. 590–599. https://doi.org/10.1111/iwj.12902.






