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Driver Capability Monitoring in Highly Automated Driving: from state to capability monitoring
(2015)
Since the early 1980s, shock wave treatment has been the golden standard treatment option for the disintegration of kidney stones in urology. A wide range of beneficial effects of shock waves on the human body was soon identified, starting with first observations of bone densification at the iliac crest after treatment of kidney stones. Since then, the indications for shock wave therapy have conquered areas apart from the field of urology. Nowadays, shock wave therapy is used for a variety of indications such as tendinopathies or impaired bone healing.
Furthermore, patients suffering from poor wound healing such as diabetic foot ulcers and also chronic, non-healing wounds are treated successfully with shock waves. Despite the versatile application fields of shock wave therapy, the general principles underlying the beneficial effect of this treatment still remain to be fully elucidated. Several in vitro and in vivo studies, mostly involving osteoblast like cells and the osteo-inductive potential of shock wave treatment, already highlighted the role of the activation of mechanotransductory signaling pathways. For the clinical application of shock wave therapy as an accepted treatment for critically healing wounds (e.g. chronic or diabetic wounds, burns), general mechanistic evidence to explain the underlying mechanisms is essential. These data would facilitate the standardized application of this non-invasive, cost efficient and low- risk bearing therapy, which can be performed in an outpatient setting.
First of all, an in vitro set-up was established and the necessary technical parameters for the optimal application of shock wave treatment on cell cultures were defined in this thesis. For this purpose, a molecule uptake assay was used as a functional assay. The following aims of this study were to elucidate the effect of shock wave treatment on intracellular signaling in vitro and to ultimately describe their role in the wound healing effect of shock wave treatment in vivo. To identify universal effects of shock wave treatment on intracellular signaling mechanisms, various cell lines were used, including the human U937 monocytic cell line, a human Jurkat T-cell line, the human MG63 osteosarcoma cell line, the C3H10T1/2 mouse mesenchymal progenitor cell line as well as primary human peripheral mononuclear cells. For the first time, the affected signaling cascade leading to the proliferative effect of shock wave treatment in vitro was described in detail in mouse C3H10T1/2 cells as well as in human adipose tissue-derived stem cells and human Jurkat T-cells. Further, ATP release from shock wave treated cells was shown to initiate intracellular Erk1/2 signaling activation via purinergic signaling. The thereby ultimately increased proliferation was reported to be dependent on shock wave treatment triggered Erk1/2 pathway activation. An in vivo study on impaired wound healing in rats confirmed the hypothesis on the essential role of Erk1/2 signaling in the shock wave treatment induced wound healing effect. Data clearly indicate the crucial importance of the Erk1/2 signaling cascade in the proliferative and wound healing effect of shock wave treatment.
Conclusively, purinergic signaling activated Erk1/2 signaling cascades play an essential role in the shock wave treatment induced proliferative and wound healing effect. The thereby broadened knowledge on the underlying mechanistic principles of the effect of shock wave treatment contributes to the establishment of shock wave therapy as a feasible standard treatment for soft tissue wound healing disorders such as diabetic or chronic wounds.