Rapamycin limits peritendinous fibrosis but does not affect intratendinous healing in a rodent Achilles tendon injury model
Tendon  injuries are common, affecting both athletes and the general population. Healing is often poor, with deposition of fibrotic, disorganised scar-like tissue leading to continued pain, dysfunction and reinjury. While a variety of therapeutics are available clinically to treat tendon injuries, outcomes remain variable and no treatments are able to fully restore tendon structure and function, hence novel regenerative therapies are required. The pathogenesis of many fibrotic diseases is influenced by the mammalian target of rapamycin (mTOR) signalling pathway, which modulates processes required for cell growth and proliferation. Rapamycin, an mTOR inhibitor, is a promising therapeutic for several fibrotic diseases, and can facilitate musculoskeletal tissue repair. Therefore, we used a needle injury model in the rat Achilles tendon to test the hypothesis that rapamycin treatment during the early stages of tendon injury enhances tendon healing via modulation of resident tendon cell populations and autophagy. The results demonstrate that, while rapamycin treatment decreased peritendinous fibrosis and appeared to modulate cell recruitment, it did not enhance healing of lesions within the tendon core, up to three weeks post-injury. Therefore, rapamycin is not an effective therapeutic for tendon injury in young adults. Future studies should establish if rapamycin is able to improve tendon healing in aged animals or with longer-term administration. Overall design: RNAseq profiling of Evs isolated from serum of rats subjected to tendon injury and treated either with rapamycin or vehicle control, 7 or 21 days post injury