When Waves Meet Biology:

A Closer Look at Tissue, Cells and the Response to Spark Wave Therapy

Biological
Working Mechanism

The physical energy of shockwaves induces mechanical stimulation that propagates through the tissue and is detected by mechanoreceptors in the cell membrane. This mechanical input is translated into a cascade of biological responses. Scientific studies have shown that shockwaves enhance cellular metabolism, increase protein expression, stimulate cell proliferation, and trigger the recruitment of mesenchymal and hematopoietic stem cells. Together, these biological processes lead to clinically relevant outcomes such as pain reduction, improved blood circulation, decreased inflammation, and enhanced tissue repair and regeneration.

Biological Effect

Clinical Impact

Biological Effect

INCREASED CELL METABOLISM

Shockwave therapy triggers the release of ATP from cells. These signalling molecules bind to specific receptors leading to accelerated cellular metabolic activity and increased energy availability for various cellular functions. [1] [8]

ENHANCED PROTEIN EXPRESSION

Activated signalling pathways promote protein production, needed for tissue repair. Newly built proteins contribute to the cellular cascade of healing. [1] [8]

STEM CELL RECRUITMENT

Stimulation of integrins and mechanosensitive ion channels lead to the release of chemokines and growth factors. These cues create local gradients and increase adhesion, guiding circulating stem cells to the injury site to accelerate tissue regeneration. [1] [8]

CELL PROLIFERATION

The combination of activated biological pathways and the formation of new proteins eventually lead to cell growth and production. [1] [8]

Spark Wave Treatment (electrohydraulic shockwave treatment) of an orthopaedic indication

Clinical Impact

PAIN RELIEF

Extracorporeal Shockwave Therapy (ESWT) delivers powerful pain relief through multiple scientifically proven mechanisms, including:

Targeted Reduction of Nerve Fibers:

Decrease of small sensory unmyelinated nerve fibres that contribute to pain perception. 

Lowering Pain-Related Substances:

Lower levels of pain-related neuropeptides, such as Substance P and CGRP.

Hyperstimulation for Pain Modulation:

Desensitization of the affected area by stimulating nociceptors. 

Optimizing Pain Signal Transmission:

Altered pain signal transmission reduces discomfort over time.

[2] [3]

ANTI-INFLAMMATORY EFFECT

Modulation of nociceptive signal transmission: Shockwave therapy reduces the activity of pain-conducting nerve cells.

ESWT modulates inflammatory processes, particularly through its effects on macrophage populations. This optimizes the balance between pro-inflammatory M1 and anti-inflammatory M2 macrophages, promoting faster healing and tissue repair.

Activation of Toll-like receptor 3 (TLR3):

TLR3 modulates inflammation, stimulates regenerative cytokines, and promotes angiogenesis through VEGF upregulation. 

Macrophage Transition:

ESWT facilitates the shift from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages.  

Reduced Inflammation:

Increased immune modulation is crucial for resolving inflammation and initiating the healing process. 

[5] [6] [9]

IMPROVED BLOOD SUPPLY -
BLOOD VESSEL FORMATION

Repeated shockwave application leads to a measurable reduction in inflammation.

Mechanical stimuli lead to the release of growth factors, involved in a chain reaction of signalling pathways.

Increased blood supply:

Stimulation of the production of endothelial nitric oxide synthase (eNOS). This enzyme is responsible for generating nitric oxide (NO), a potent vasodilator that improves blood flow by relaxing blood vessels.

Formation of blood vessels:

The activation of endothelial cells upregulates the expression of Vascular Endothelial Growth Factor (VEGF), which is a key regulator of angiogenesis and neovascularization.  

[4]

TISSUE FORMATION & REGENERATION

Increased erythrocyte flow indicates enhanced blood circulation following shockwave treatment.

A key aspect of shockwave therapy is the process of the recruitment and activation of stem cells, which play a crucial role in tissue regeneration and repair.

Tissue Formation:

Activation of membrane proteins like integrins and adhesion molecules, ensuring that these regenerative cells attach, proliferate, and differentiate into functional tissue. 

Collagen Synthesis and Tissue Remodelling:

Promotion of collagen synthesis, a key structural protein in connective tissues. This increased collagen production contributes to improved tissue strength and integrity, facilitating the remodelling process essential for long-term healing. 

[2] [6] [7]

Extracorporeal Shockwave Therapy Mechanism in Musculoskeletal Regenerative Medicine

Progressive cellular repopulation visualizes tissue regeneration initiated by shock wave.

References

Szwarc-Hofbauer, D.; Simböck, E.; Hromada, C.; Stoiber, M.; Tomasch, J.; Weitzer, G.; Teuschl-Woller, A. Purinergic Receptors Play a Key Role in Shock Wave-Induced Proliferation. Sci Rep 2025, 15 (1), 19138.
Simplicio CL, Purita J, Murrell W, Santos GS, Dos Santos RG, Lana JFSD. Extracorporeal shock wave therapy mechanisms in musculoskeletal regenerative medicine. J Clin Orthop Trauma. 2020 May
Ryskalin, L.; Morucci, G.; Natale, G.; Soldani, P.; Gesi, M. Molecular Mechanisms Underlying the Pain-Relieving Effects of Extracorporeal Shock Wave Therapy: A Focus on Fascia Nociceptors. Life 2022
Mittermayr, R.; Hartinger, J.; Antonic, V.; Meinl, A.; Pfeifer, S.; Stojadinovic, A.; Schaden, W.; Redl, H. Extracorporeal Shock Wave Therapy (ESWT) Minimizes Ischemic Tissue Necrosis Irrespective of Application Time and Promotes Tissue Revascularization by Stimulating Angiogenesis. Annals of Surgery 2011, 253 (5), 1024–1032
Tepeköylü, C.; Lobenwein, D.; Urbschat, A.; Graber, M.; Pechriggl, E. J.; Fritsch, H.; Paulus, P.; Grimm, M.; Holfeld, J. Shock Wave Treatment after Hindlimb Ischaemia Results in Increased Perfusion and M2 Macrophage Presence: SWT Induces Angiogenesis Ischaemic Muscle via Macrophage Recruitment. J Tissue Eng Regen Med 2018, 12 (1), e486–e494.
d’Agostino, M. C.; Craig, K.; Tibalt, E.; Respizzi, S. Shock Wave as Biological Therapeutic Tool: From Mechanical Stimulation to Recovery and Healing, through Mechanotransduction. International Journal of Surgery 2015, 24, 147–153.
Saggini, R.; Saggini, A.; Spagnoli, A. M.; Dodaj, I.; Cigna, E.; Maruccia, M.; Soda, G.; Bellomo, R. G.; Scuderi, N. Extracorporeal Shock Wave Therapy: An Emerging Treatment Modality for Retracting Scars of the Hands. Ultrasound in Medicine & Biology 2016, 42 (1), 185–195.
Basoli, V.; Chaudary, S.; Cruciani, S.; Santaniello, S.; Balzano, F.; Ventura, C.; Redl, H.; Dungel, P.; Maioli, M. Mechanical Stimulation of Fibroblasts by Extracorporeal Shock Waves: Modulation of Cell Activation and Proliferation Through a Transient Proinflammatory Milieu. Cell Transplant 2020, 29, 096368972091617.
Holsapple, J. S.; Cooper, B.; Berry, S. H.; Staniszewska, A.; Dickson, B. M.; Taylor, J. A.; Bachoo, P.; Wilson, H. M. Low Intensity Shockwave Treatment Modulates Macrophage Functions Beneficial to Healing Chronic Wounds. IJMS 2021, 22 (15), 7844.