Focused Ultrasound Therapies for the Non-Invasive Treatment of Tendinopathies - PROJECT SUMMARY Achilles tendinopathy is a disabling, often painful condition that can progress to further degenerative tissue changes or result in tendon rupture if not effectively managed. It is widely held that therapeutic mechano- transduction processes promote healing of the injured tendon. Clinical ultrasound therapies deliver energy in the form of propagated sound waves to targeted tissues. However, current therapeutic ultrasound treatments commonly provide minimal mechanical stimulation of the injured tendon. Focused ultrasound (FUS) is an emerging, non-invasive therapy capable of inducing bio-effects through mechanical and/or thermal mechanisms with high spatial and temporal precision. Recent pre-clinical tendon models have demonstrated the potential of FUS to achieve mechanical fractionation with no deleterious effects on tendon function or healing; however, no studies have investigated FUS as a rehabilitative loading treatment for tendinopathy. The primary objectives of this study are to (1) utilize numerical modeling to establish FUS protocols for precise acoustic stimulation of murine Achilles tendons, (2) identify FUS stimulation parameters for effective in vivo treatment of murine Achilles tendinopathy, and (3) characterize the cell and matrix responses associated with distinct FUS stimulation regimes. We will first develop an integrated computational modeling - experimental approach to characterize ex vivo tendon temperature changes and mechanical strain under a range of FUS treatment parameters (Aim 1). Protocols developed in Aim 1 will then be applied towards in vivo FUS treatments of injured tendons, with healing assessed using biomechanical, histologic, and cell biologic outcomes (Aim 2). We hypothesize that (a) the application of FUS will augment healing of injured Achilles tendons, and that (b) mechanical FUS regimes will be more effective than thermal FUS regimes. Successful demonstration of the potential of FUS to stimulate tendon healing will considerably strengthen the rationale for using FUS as a non-invasive, rehabilitative treatment method for tendinopathy and provide encouraging evidence of a potentially effective alternative over existing ultrasound therapies for tendon injuries. Furthermore, our project will generate novel insights into the relationships between acoustic stimulation parameters and tendon mechanotransduction. Finally, this project will establish a modular, scalable experimental platform upon which future studies in larger species and/or different tendon types can readily be undertaken.
