Initiation Timing of Low-Intensity Pulsed Ultrasound Stimulation for Tendon-Bone Healing in a Rabbit Model

Background: Low-intensity pulsed ultrasound stimulation (LIPUS) has been proven to be a beneficial biophysical therapy for tendon-bone (T-B) healing. However, the optimal time to initiate LIPUS treatment has not been determined yet. LIPUS initiated at different stages of the inflammatory phase may profoundly affect T-B healing. Purpose: An established rabbit model was used to preliminarily investigate the effect of LIPUS initiation timing on T-B healing. Study Design: Controlled laboratory study. Methods: A total of 112 mature rabbits that underwent partial patellectomy were randomly assigned to 4 groups: daily mock sonication (control group) and daily ultrasonication started immediately postoperatively (immediate group), on postoperative day 7 (7-day delayed group), or on postoperative day 14 (14-day delayed group). Peripheral leukocyte counts at the inflammatory phase were used to assess postoperative inflammation. The rabbits were sacrificed at 8 or 16 weeks postoperatively for microarchitectural, histological, and mechanical evaluations of the patella–patellar tendon (PPT) junction. Results: The biomechanical properties of the PPT junction were significantly improved in the LIPUS-treated groups. Significantly higher ultimate strength and stiffness were seen in the 7-day delayed group compared with the other groups at 8 weeks postoperatively ( P < .05 for all). Newly formed bone expansion from the remaining patella in the ultrasonic treatment groups was significantly increased and remodeled compared with the control group. Micro–computed tomography analysis showed that the 7-day delayed group had significantly more bone volume and bone mineral content at the interface as compared with the other groups at 8 weeks postoperatively ( P < .05 for all). Histologically, the ultrasonic treatment groups exhibited a significantly better PPT junction, as shown by more formation and remodeling of the fibrocartilage layer and newly formed bone. Additionally, peripheral leukocyte counts displayed a significant increase from postoperative day 1 to day 3 in the immediate group as compared with the other groups. Furthermore, postoperative hydrarthrosis was more likely in the immediate group. Conclusion: LIPUS started at postoperative day 7 had a more prominent effect on T-B healing compared with the other treatment regimens in this study. Clinical Relevance: The findings of the study may help optimize the initiation timing of LIPUS for T-B healing.