Overuse injuries are common clinical problems, athletically and occupationally, with estimates that nearly 50% of all injuries are overuse. Though a major clinical issue, the underlying etiology of tendon overuse injuries is unknown. Currently, the prevailing thought centers on microdamage accumulation. This is where loading (well below failure levels) causes damage at the fibrillar level. When this damage outpaces the tendon’s ability to repair itself, then tendinopathy is thought to occur.

The elastic limit beyond which this microdamage occurs has long been accepted at 4% strain. The first objective was to examine this idea utilizing newer methodologies by first loading tendons to various subfailiure strain levels, then loading to failure after rest. The elastic limit approached the failure strain limit (16%), implicating cellular responses as the driving factor in tendinopathy.

To examine overuse tendinopathy, the next objective was to develop and characterize a model to apply and monitor complex, cyclic loadings to viable tendon. This device was able to significantly reduce the mechanical properties of loaded tendons (relative to control) as well as monitor this damage (strain accumulation).

With a model established, cyclic loadings were performed across varying periods to assess cellular responses’ role on tendon’s mechanical and biochemical characteristics. Compositional changes, as well as pronounced magnitude and duration dependant effects in collagenase, cellularity and the inflammatory mediator PGE₂ were observed. Significant loss of material properties were also observed with respect to loading magnitude. To determine the magnitude effect of these responses and separate it from duration dependence, an experiment with four levels of loading was performed across three days. This duration proved too short for compositional changes, however, significant magnitude dependant cellular responses were observed in regards to collagenase, cellularity and PGE₂.

PGE₂, long hypothesized to contribute to tendinopathy development, was examined across cyclic loadings. PGE₂ treatment caused decreased stiffness, resulting in increased strain and cellular responses. COX inhibitors were effective at reducing PGE2, as well as its responses. This study suggests PGE₂ may contribute in driving healthy tendons into tendinopathy, however this response is reducible with COX inhibitors which otherwise showed no negative effects in an explant model.