Maturation-Dependent Tendon Mechanical and Structural Response to Overload in Rat Model of Synergist Ablation

Aging musculoskeletal tissues have a progressively declining ability to maintain homeostasis, increasing the risk of tendinopathy and tendon rupture. In young rats (3 months old), in vivo mechanical overload induced adaptive changes at 8 weeks, where load-bearing ability increased, which transitioned to degenerative changes at 16-weeks, where mechanical properties declined. It is unknown how maturation will influence the timeline of tendon outcomes to overload. The primary objective of this study was to evaluate mechanical and structural responses to overload in "middle-aged" (12-month-old) rats, representing an age when human tendon injuries become more prevalent, using a synergist ablation (SynAb) model. 12-month-old rats demonstrated adaptive changes in structural properties after 8-weeks of overload and no alterations in material properties, similar to prior findings in 3-month-old rats. Contrary to our findings in young animals, middle-age animals did not exhibit mechanical degeneration but rather they returned to control levels. MRI and μCT revealed no overload-dependent differences in tissue-scale structure, tendon cellularity, and collagen organization at either timepoint. A secondary objective was to evaluate natural age-related changes in untreated tendons. Twelve-month-old tendons, compared to 3-month-old tendons, exhibited greater load bearing-capacity, reduced extensibility, increased linear modulus, more heterotopic ossification, and a shift toward rounder nuclear morphology. These findings indicate that maturation still induces an initial adaptive response but does not lead to degeneration at later timepoints, differing from younger rats.