Mechanisms of extracorporeal shock wave therapy on musculoskeletal system

Uvod: Več kot dvajset let se udarni globinski valovi uspešno uporabljajo za obravnavo različnih mišično-skeletnih okvar. Terapija z udarnimi globinskimi valovi pri tendinopatijah in drugih obolenjih gibalnega sistema velja za učinkovito, varno, neinvazivno terapijo in je brez hujših stranskih učinkov. Delovanje udarnih globinskih valov ni samo posledica neposrednega mehanskega draženja, ampak tudi različnih bioloških odgovorov na akustični dražljaj. Natančni mehanizmi delovanja na proces regeneracije tkiv gibalnega sistema še niso znani. Namen: Namen diplomskega dela je s pomočjo pregleda literature predstaviti znanstvene dokaze o mehanizmih delovanja udarnih globinskih valov na celice in tkiva. Metode dela: Izbrana metoda dela za diplomsko delo je pregled literature. Literatura je bila iskana v podatkovnih zbirkah Cochrane, ScienceDirect, PubMed in Mednar, v obdobju od avgusta 2016 do junija 2017. Rezultati: Vključitvenim in izključitvenim kriterijem je ustrezalo osem znanstvenih člankov, ki so raziskovali vpliv udarnih globinskih valov na osteoblaste, matične celice, makrofage, kožno tkivo (kožni presadek in dermalne fibroblaste) in tenocite. V študijah so analizirali vpliv udarnih globinskih valov na proliferacijo in diferenciacijo celic, izražanje genov za sintezo medceličnine, sproščanje dušikovega oksida, rastnih faktorjev in vnetnih citokinov. Razprava in sklep: Mehanizmi delovanja udarnih globinskih valov so posledica mehanotransdukcije, ki spremeni mehanski dražljaj v biološke signale v celici, kar sproži različne reakcije v tarčnem tkivu. Pri osteoblastih se po terapiji povečajo njihova proliferacija, diferenciacija, sinteza medceličnine in posledično mineralizacija tarčnega predela. Pri regeneraciji kože terapija z udarnimi globinskimi valovi poveča izražanje vazodilatatorjev v zgodnji fazi in spodbuja angiogenezo v kasnejši fazi. Pri dermalnih fibroblastih spodbudi proliferacijo, diferenciacijo in poveča izražanje genov za tvorbo kolagena. Terapija z udarnimi valovi pri tenocitih spodbudi proliferacijo, diferenciacijo in migracijo, s povečano koncentracijo rastnih faktorjev pa izražanje genov za tvorbo kolagena. Udarni globinski valovi vplivajo tudi na protivnetni odziv tkiva in ohranjajo mezenhimske markerje matičnih celic. Pravilna izbira parametrov udarnih valov ima pozitivne učinke, nepravilno doziranje pa negativne posledice. Potrebne so nadaljnje raziskave in vivo pri zdravih ljudeh in ljudeh z okvarami gibalnega sistema, ki bi ovrednotile tudi dolgoročni učinek udarnih globinskih valov.Introduction: Extracorporeal shockwave therapy has been successfully used for over 20 years to treat different orthopaedic conditions. This form of therapy is considered effective, safe, non-invasive, with little to no complications for treatment of tendinopathies and other conditions of the locomotor system. The effect of extracorporeal shock waves is not only an answer of the tissue to mechanical stimulus, but also a cascade of biological reactions of the cell through transduction of the shockwave signal into biological signals. Biomolecular mechanisms of the shockwave therapy are yet to be completely understood. Purpose: The purpose of this literature review is finding scientific evidence of biochemical mechanisms of extracorporeal shock waves on different tissues and types of cells. Methods: The method chosen for this thesis is a literature review. The literature was searched in Cochrane, ScienceDirect, PubMed and Mednar databases form August 2016 to June 2017. Results: Eight studies fit the inclusion and exclusion criteria and they researched the effect of extracorporeal shock waves on osteoblasts, stem cells, macrophages, skin tissue (skin flap, dermal fibroblasts) and tenocytes. They analysed proliferation, differentiation, expression of genes responsible for the synthesis of extracellular matrix, the concentration of nitric oxide, growth factors and inflammatory cytokines. Discussion and conclusion: The mechanism behind the effects of extracorporeal shock wave therapy is mechanotransduction, which transforms mechanical signal into a biological reaction in the target issue. After the shockwave therapy, there is an increase in proliferation, differentiation, matrix synthesis and consequently an increase in mineralization in osteoblasts. In skin regeneration, shockwaves increase the expression of vasodilatation factors in the early stages, and angiogenesis in late stages of regeneration. In dermal fibroblasts, it promotes proliferation, differentiation and expression of genes for the synthesis of collagen. In tenocytes, shockwave therapy improved proliferation, differentiation and collagen synthesis with increased levels of growth factors. Extracorporeal shockwaves also effect anti-inflammatory response and improve expression of mesenchymal markers of stem cells. The correct dosage of shockwaves has positive outcomes, but the wrong choice of parameters can lead to negative outcomes. However, long term outcomes and in vivo mechanisms on healthy and pathological tissues should be further investigated