Application of Focused Ultrasound for the Treatment of Tendinopathy: An In Vivo Feasibility, Safety, and Efficacy Study.

Mechanical loading-based rehabilitation of tendinopathies improves symptoms and tendon biomechanics, motivating interest in non-invasive treatment options. Focused ultrasound (FUS) is a promising technology that precisely targets tissue regions, inducing desired bioeffects while minimally affecting surrounding tissues. To explore its potential for treating tendinopathies, we sequentially characterized FUS-induced tendon temperature elevations ex vivo, treated uninjured mouse Achilles tendons in vivo, and finally assessed the in vivo effects of FUS treatment of tendinopathic tissues. FUS (1.1 MHz transducer) consisted of thermal-dominant (0.5 MPa peak-peak pressure, continuous pulsing, 100% duty cycle) or mechanical-dominant (2 or 5 MPa, 10 Hz, 1% duty cycle) pulsing for four sessions over 1 week. No adverse events were observed, and mice did not exhibit pain or distress. Relative to untreated tendons, thermal FUS treatment of uninjured tendons did not alter mechanical properties while mechanical (5 MPa) FUS treatment significantly reduced maximum stress and elastic modulus. Tendons from both treatments exhibited mild matrix disorganization and increased cellularity, indicating an adaptive response. When applied to injured tendons, mechanical (5 MPa) FUS treatment reduced cross-sectional area and restored elastic modulus and yield stress to levels of naïve tendons. Although signs of injury persisted, the FUS-treated region exhibited fewer rounded cells and a reduction in sulfated glycosaminoglycan deposits, indicative of injury improvement. These pre-clinical studies demonstrate the safety, feasibility and preliminary efficacy of FUS for tendinopathy treatment. This foundational methodology facilitates further exploration of acoustic treatment parameters and strategies to augment tendon healing.