Extracorporeal shockwaves as regenerative therapy in orthopedic traumatology: a narrative review from basic research to clinical practice.

Extracorporeal Shock Wave Therapy (ESWT), after its first medical application in the urological field for lithotripsy, nowadays represents a valid therapeutical tool also for many musculoskeletal diseases, as well as for regenerative medicine applications. This is possible thanks to its mechanisms of action, which in the non-urological field are not related to mechanical disruption (as for renal stones), but rather to the capacity, by mechanotransduction, to induce neoangiogenesis, osteogenesis and to improve local tissue trophism, regeneration and remodeling, through stem cell stimulation. On the basis of these biological assumptions, it becomes clear that ESWT can represent a valid therapeutic tool also for all those pathological conditions that derive from musculoskeletal trauma, and are characterized by tissue loss and/or delayed healing and regeneration (mainly bone and skin, but not only). As a safe, repeatable and non–invasive therapy, in many cases it can represent a first–line therapeutic option, as an alternative to surgery (for example, in bone and skin healing disorders), or in combination with some other treatment options. It is hoped that with its use in daily practice also the muscle–skeletal field will grow, not only for standard indications, but also in post–traumatic sequelae, in order to improve recovery and shorten healing time, with undoubted advantages for the patients and lower health service expenses.

Early angiogenic response to shock waves in a three-dimensional model of human microvascular endothelial cell culture (HMEC-1).

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.

Extracorporeal shock wave therapy for the treatment of osteonecrosis and bone vascular diseases: a systematic review of randomized controlled trials.

OBJECTIVE: The aim of the study is to review the available literature on the use of Extracorporeal Shock Wave Therapy (ESWT) for the treatment of osteonecrosis (ON) and bone vascular disease (BVD), to understand its therapeutic potential and compare it with other therapies. MATERIALS AND METHODS: A systematic review was performed on the PubMed, Scopus, Science Direct, and Research Gate databases with the following inclusion criteria: 1) randomized controlled trials (RCTs); 2) written in English; 3) published in indexed journals within the last 25 years (1995-2020); and 4) dealing with the use of ESWT for the treatment of BVD or ON. The risk of bias was assessed by the Cochrane Risk of Bias tool for RCTs. RESULTS: Five studies involving 199 patients in total (68 female and 131 male) were included. Patients in the control groups received different treatments, like surgery, bisphosphonates in combination with prostacyclin or ESWT, and hyperbaric oxygen therapy. Looking at the quality of the available literature, none of the studies included could be considered a "good quality" study; only one was ranked as "fair" and the remaining were marked "poor" quality studies. No major complications or serious adverse events were reported in any of the included studies. Based on the available data, ESWT can produce rapid pain relief and functional improvement. CONCLUSIONS: Overall, a substandard quality of method emerged from the analysis of the literature, with most studies flawed by relevant bias. Ultimately, ESWT has the potential to be a useful conservative treatment in bone degeneration due to vascular and tissue turnover impairment.

Shock wave as biological therapeutic tool: From mechanical stimulation to recovery and healing, through mechanotransduction.

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.