Low-Intensity Pulsed Ultrasound Augments Tendon, Ligament, and Bone-Soft Tissue Healing in Preclinical Animal Models: A Systematic Review

Purpose: To appraise the available animal and human studies investigating low-intensity pulsed ultrasound stimulation (LIPUS) on tendon, ligament, and bone-soft tissue (B-ST) junction healing. Methods: A systematic review of PUBMED, EMBASE, and the Cochrane Library was performed for animal and human studies investigating the effects of LIPUS on tendon, ligament, and B-ST junction healing. The systematic search was performed using the key term "low intensity pulsed ultrasound" and any of the following: "tendon," "ligament," "tendon-bone," and "bone-tendon." Inclusion criteria consisted of (1) randomized controlled trials assessing the effect of LIPUS on bone, tendon, and soft tissue in animals or humans and (2) English-language articles. Results: A total of 28 animal and 2 human studies met inclusion criteria. Animal studies utilized various models, including Achilles and patellar tendon transections, medial collateral ligament transections, and surgical repair of patellar tendon, rotator cuff tendon, and anterior cruciate ligament, to evaluate the effects of LIPUS. Animal studies demonstrated significantly improved collagen content and organization, bone formation, fibrocartilage remodeling, and mechanical strength with LIPUS treatment compared with controls. In human trials, LIPUS treatment of chronic tendinopathies did not improve clinical outcomes. Conclusions: In acute injury animal models, LIPUS augmented healing of acute tendon, ligament, and B-ST junction injuries through increased collagen content and organization; increased antiinflammatory cellular signaling; and increased angiogenesis. However, in 2 human studies investigating chronic tendinopathy, LIPUS did not lead to superior outcomes compared with controls. Clinical Relevance: Animal models suggest that LIPUS may be a promising noninvasive treatment modality for accelerating patient recovery after acute tendon and ligament injuries, as well as after surgical repair of B-ST junction injuries, but this has not been demonstrated in human studies. Randomized clinical trials evaluating LIPUS for acute tendon and ligament injuries are warranted.