Comparative Analysis of Tendon Healing in a Clinically Relevant Mouse Model of Achilles Tendon Repair.

Adult tendon injuries are common and debilitating, with limited regenerative potential. In recent years, the mouse has emerged as a potent tool to identify cell and molecular mechanisms of healing and test novel biologics, however injury models frequently vary between studies. Both non-reconstructive injuries (such as full or partial tenotomies or window defects), as well as full tenotomy followed by surgical repair have been applied. However, direct comparisons of healing between reconstructive and non-reconstructive approaches have rarely been carried out. In this study, we compare three clinically relevant injury models in the Achilles tendon: tenotomy-only injury, tenotomy with cast immobilization, and tenotomy with microsurgical repair and cast immobilization. We find that surgical repair resulted in the most improved functional recovery, with lowest recruitment of inflammatory macrophages, enhanced tenogenic gene expression, and reduced fibrotic gene expression. Lineage tracing further showed enhanced recruitment of Scleraxis-lineage tenocytes. Collectively, these results suggest that there are distinct differences in functional, cellular, and molecular outcomes with and without surgical repair following tenotomy. These differences in healing may be considered when selecting the most appropriate injury model for specific scientific questions.