For almost 30 years, extracorporeal shock wave therapy has been clinically implemented as an effective treatment to disintegrate urinary stones. This technology has also emerged as an effective noninvasive treatment modality for several orthopedic and traumatic indications including problematic soft tissue wounds. Delayed/nonhealing or chronic wounds constitute a burden for each patient affected, significantly impairing quality of life. Intensive wound care is required, and this places an enormous burden on society in terms of lost productivity and healthcare costs. Therefore, cost-effective, noninvasive, and efficacious treatments are imperative to achieve both (accelerated and complete) healing of problematic wounds and reduce treatment-related costs. Several experimental and clinical studies show efficacy for extracorporeal shock wave therapy as means to accelerate tissue repair and regeneration in various wounds. However, the biomolecular mechanism by which this treatment modality exerts its therapeutic effects remains unclear. Potential mechanisms, which are discussed herein, include initial neovascularization with ensuing durable and functional angiogenesis. Furthermore, recruitment of mesenchymal stem cells, stimulated cell proliferation and differentiation, and anti-inflammatory and antimicrobial effects as well as suppression of nociception are considered important facets of the biological responses to therapeutic shock waves. This review aims to provide an overview of shock wave therapy, its history and development as well as its current place in clinical practice. Recent research advances are discussed emphasizing the role of extracorporeal shock wave therapy in soft tissue wound healing.

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Significance Inducing the growth of new blood vessels by specific factors is an attractive strategy to restore blood flow in ischemic tissues. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, yet clinical trials of VEGF gene delivery failed. Major challenges include the need to control the tissue distribution of factor dose and the duration of expression. Here, we developed a highly tunable fibrin-based platform to precisely control the dose and duration of VEGF protein delivery in tissues. Optimized delivery of fibrin-bound VEGF ensured normal, stable, and functional angiogenesis and improved perfusion of ischemic tissues, without genetic modification and with limited duration of VEGF delivery. These findings suggest a strategy to improve both safety and efficacy of therapeutic angiogenesis.