Biological effects of extracorporeal shock waves on fibroblasts. A review

Tissue homeostasis is influenced by mechanical forces which regulate the normal function of connective tissues. Mechanotransduction, the process that transforms mechanical stimuli in chemical signals, involves mechanosensory units integrated in cell membrane. The mechanosensory units are able to activate gene expression for growth factors or cytochines as well as to induce a biological event which results in cell proliferation and/or differentiation. In connective tissue the fibroblasts are the cells more represented and are considered as a model of mechanosensitive cells. They are ubiquitous but specific for each type of tissue. Their heterogeneity consists in different morphological features and activity; the common function is the mechanosensitivity, the capacity to adhere to extracellular matrix (ECM) and to each other, the secretion of growth factors and ECM components. Extracorporeal shock waves (ESW) have been recently used to treat damaged osteotendineous tissues. Studies in vitro and in vivo confirmed that ESW treatment enhances fibroblast proliferation and differentiation by activation of gene expression for transforming growth factor β1 (TGF- β1) and Collagen Types I and III. In addition, an increase of nitric oxide (NO) release is even reported in early stage of the treatment and the subsequent activation of endothelial nitric oxide synthase (eNOS) and of vascular endothelial growth factor (VEGF) are related to TGF- β1 rise. The data have been related to the increase of angiogenesis observed in ESW treated tendons, an additional factor in accelerating the repairing process. A suitable treatment condition, characterized by a proper energy/shot number ratio, is the basis of treatment efficacy. Further ESWT applications are suggested in regenerative medicine, in all cases where fibroblast activity and the interaction with connective tissue can be positively influenced.