The effect of therapeutic ultrasound on tendon healing and sensory nerve regeneration after Achilles tendon rupture

Objectives. The underlying mechanisms of the effect of therapeutic ultrasound in promoting healing of Achilles tendon rupture are still not well understood. Recent immunochemical studies on the injured rat's Achilles tendon showed in-growth of different types of sensory nerve fibers at the early stage of healing, suggesting the importance of the role of intact sensory function in tendon repair. The purpose of this study was to investigate the role of the sensory nerve in tendon healing and its response to ultrasound stimulation in enhancing tendon healing.;Methods. A series of animal studies were carried out on totally 128 rats. The tendon injury model was the right medial Achilles tendon hemi-tenotomy. Pulsed ultrasound (PUS) was used for ultrasonic therapy. Animals were then randomly assigned equally into 4 groups: two neural intact groups received treatment of either sham PUS (control group) or true PUS (PUS group) to the injured area: the rats in the other 2 groups received an additional ipsilateral sciatic neurectomy (SN) and then the injured tendons were treated either by sham PUS (SN-control group) or true PUS (SN-PUS group). The animals were sacrificed at 2 or 4 weeks postinjury and bilateral Achilles tendons were harvested for biomechanical and histological analysis or immunohistochemical analysis.;Results. Two-way Analysis of Variance (ANOVA) on the biomechanical testing data showed that the PUS group had significantly higher normalized UTS and stiffness than the control group (p<0.01) in animals with intact nerve supply. However, in animals with sciatic neurectomy, no significant difference was found (p>0.05). Besides, the UTS of the injured leg in SN-contol group was significantly lower than that of the control group at 4 weeks postinjury.;In animals with intact neural supply, the collagen matrix was denser and the alignment of collagen fiber bundles more regular in the PUS group. However, in animals with sciatic neurectomy, the injured tendon was healed by scar tissue with inferior properties revealed by high cellularity, a lower portion of collagen matrix, and a higher fusifomi fibroblast to mature tenocytes ratio throughout the 4 weeks. There was no significant difference in the morphological appearance of the healing area between the SN-PUS and SN-control groups.;Immunohistochemical analysis on tendons with intact neural supply revealed a significantly higher invasion of CGRP positive nerve fibers in the PUS group at 2 weeks postinjury, while this difference was not found in the 2 groups with sciatic neurectomy. These results suggest a possible interaction between CGRP positive sensory nerve fibers and PUS in promoting tendon healing.;Conclusion. Results of this study suggested that PUS can improve tendon healing only when there is an intact nerve supply. Denervation impacted the tendon healing. This study suggests the importance of the involvement of neurological components in ultrasound-enhanced tendon healing and the vital role of tendon innervation.