Multiscale mechanisms of tendon fatigue damage progression and severity are strain and cycle dependent

Stephen J. Ros, Patrick M. Muljadi, Evan L. Flatow, Nelly Andarawis-Puri

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Tendinopathies are common chronic injuries that occur when damage accumulation caused by sub-rupture fatigue loading outpaces repair. Studies have linked fatigue loading with various mechanical, structural, and biological changes associated with pathology. However, the multiscale progression of damage accumulation with respect to area, severity and the distinct contributions of strain level and number of cycles has not been fully elucidated. The objective of this study was to investigate multiscale mechanisms underlying fatigue damage accumulation and their effect on the cellular environment. Using an in situ model in rat tail tendon (RTT), fatigue loading was applied at various strains and cycle numbers to induce fatigue damage. Pre- and post- fatigue diagnostic mechanical testing, second harmonic generation (SHG) imaging, and transmission electron microscope (TEM) imaging were used to investigate extracellular and cellular damage modes at multiple scales. Fatigue loading at strains at or below 1.0% resulted in no significant changes in SHG damage area or severity and no changes in collagen fibril or cell morphology compared with controls. Fatigue loading at strains above 1.5% resulted in greater mechanical changes correlated with increased damage area measured by SHG and collagenous damage observed by TEM. Increased cycles at high strain further altered mechanical properties, increased structural damage severity (but not area), and altered TEM collagen rupture patterns. Cell morphology was similarly progressively affected with increased strain and cycle number. These damage mechanisms that may trigger degenerative changes characteristic of tendinopathy could be targeted as a part of prevention or therapy.

Original languageEnglish
Pages (from-to)148-156
Number of pages9
JournalJournal of Biomechanics
StatePublished - 6 Mar 2019


  • Electron microscopy
  • Fatigue damage
  • Microstructure
  • Second harmonic generation
  • Tendinopathy


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