Relationship between muscle pathology and tendon collagen organization in patients undergoing below-knee amputation

Muscles and tendons are routinely studied in isolation, limiting our understanding of how treatments or pathologies in one component of the musculotendinous unit affect or co-occur in the other. The purpose of this cross-sectional study was to examine baseline relationships between muscle and tendon components. Tendon and muscle specimens were obtained from individuals undergoing lower extremity amputation (age range: 37–65). Tensile mechanical testing with quantitative polarized light imaging quantified tendon mechanical properties and collagen alignment. Muscle biopsies obtained from the same muscle-tendon unit were assessed with histology (i.e. area fractions of extracellular matrix, intramuscular adipose tissue, neuropathy, and centrally nucleated fibers). Relationships in intramuscular/intratendinous lipid were assessed, and distributions of type I and III collagen tendon matrix components were evaluated. Statistically significant bivariate correlations were observed between muscle pathology (extracellular matrix, intramuscular adipose tissue, and neuropathy) and tendon collagen organization. Muscles with greater areas of pathology were connected to tendons with more aligned collagen. Muscle extracellular matrix and intramuscular adipose tissue explained the most variance in tendon collagen organization. There was no relationship between intramuscular and intratendinous lipid, and both lipid and collagen III were primarily within the intrafascicular and perivascular space within the tendon. Contrary to our hypothesis, muscle-tendon units with greater muscle pathology had tendons with more aligned collagen. These findings highlight the importance of assessing both tendon and muscle characteristics, as dysfunction in one component may not be shared with the other component.