Dynamic Tensile Stress Promotes Regeneration of Achilles Tendon in a Panda Rope Bridge Technique Mice Model.

Abstract

Regeneration of ruptured Achilles tendon remains a clinical challenge owing to its limited regenerative capacity. Dynamic tensile stress plays a positive role in the regeneration of tendon, although the specific underlying mechanisms remain unclear. In this study, the Achilles tendon defect-regeneration model was created in male C57BL/6 mice aged 8weeks. The animals were randomly assigned to four groups-repair, non-repair, repair with fixation, and non-repair with fixation. The repair groupand repair with fixation group adopted the panda rope bridge technique (PRBT) repair method. Our results demonstrated the presence of more densely aligned and mature collagen fibers, as well as more tendon-related makers, in the repair group at both 2- and 4-week post-surgery. Furthermore, the biomechanical strength of the regenerated tendon in the repair group was highly improved. Most importantly, the expressions of integrin αv and its downstream and the phosphorylation levels of FAK and ERK were remarkably higher in the repair group than in the other groups. Furthermore, blocking FAK or ERK with selective inhibitors PF573228 and U0126 resulted in obvious adverse effects on the histological structure of the regenerated Achilles tendon. In summary, this study demonstrated that dynamic tensile stress based on the PRBT could effectively promote the regeneration of the Achilles tendon, suggesting that dynamic tensile stress enhances the cell proliferation and tenogenic differentiation via the activation of the integrin/FAK/ERK signaling pathway.