Novel animal model for Achilles tendinopathy: Controlled experimental study of serial injections of collagenase in rabbits

PLoS One. 2018 Feb 13;13(2):e0192769. doi: 10.1371/journal.pone.0192769. eCollection 2018.


Our goal was to develop a novel technique for inducing Achilles tendinopathy in animal models which more accurately represents the progressive histological and biomechanical characteristic of chronic Achilles tendinopathy in humans. In this animal research study, forty-five rabbits were randomly assigned to three groups and given bilateral Achilles injections. Low dose (LD group) (n = 18) underwent a novel technique with three low-dose (0.1mg) injections of collagenase that were separated by two weeks, the high dose group (HD) (n = 18) underwent traditional single high-dose (0.3mg) injections, and the third group were controls (n = 9). Six rabbits were sacrificed from each experimental group (LD and HD) at 10, 12 and 16 weeks. Control animals were sacrificed after 16 weeks. Histological and biomechanical properties were then compared in all three groups. At 10 weeks, Bonar score and tendon cross sectional area was highest in HD group, with impaired biomechanical properties compared to LD group. At 12 weeks, Bonar score was higher in LD group, with similar biomechanical findings when compared to HD group. After 16 weeks, Bonar score was significantly increased for both LD group (11,8±2,28) and HD group (5,6±2,51), when compared to controls (2±0,76). LD group showed more pronounced histological and biomechanical findings, including cross sectional area of the tendon, Young's modulus, yield stress and ultimate tensile strength. In conclusion, Achilles tendinopathy in animal models that were induced by serial injections of low-dose collagenase showed more pronounced histological and biomechanical findings after 16 weeks than traditional techniques, mimicking better the progressive and chronic characteristic of the tendinopathy in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / pathology*
  • Animals
  • Biomechanical Phenomena
  • Collagenases / administration & dosage*
  • Disease Models, Animal*
  • Female
  • Rabbits
  • Tendinopathy / chemically induced*
  • Tendinopathy / pathology


  • Collagenases

Grant support

This study was funded by the Brazilian Government Agency: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), URL: