How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks? Interplay between early regeneration and mechanical stimulation

Background Mechanical stimulation improves the repair of ruptured tendons. Injection of a platelet concentrate (platelet-rich plasma, PRP) can also improve repair in several animal models. In a rat Achilles tendon transection model, 1 postoperative injection resulted in increased strength after 4 weeks. Considering the short half-lives of factors released by platelets, this very late effect calls for an explanation. Methods We studied the effects of platelets on Achilles tendon regenerates in rats 3, 5 and 14 days after transection. The tendons were either unloaded by Botulinum toxin A (Botox) injections into the calf muscles, or mechanically stimulated in activity cages. No Botox injections and ordinary cages, respectively, served as controls. Repair was evaluated by tensile testing. Results At 14 days, unloading (with Botox) abolished any effect of the platelets and reduced the mechanical properties of the repair tissue to less than half of normal. Thus, some mechanical stimulation is a prerequisite for the effect of platelets at 14 days. Without Botox, both activity and platelets increased repair independently of each other. However, at 3 and 5 days, platelets improved the mechanical properties in Botox-treated rats. Interpretation Platelets influence only the early phases of regeneration, but this allows mechanical stimulation to start driving neo-tendon development at an earlier time point, which kept it constantly ahead of the controls.