Tendinopathy accounts for 30-50% of musculoskeletal complaints presented to clinicians and causes chronic pain and impaired mobility in an estimated 127 million people annually. Tendinopathy is thought to arise from accumulated tissue microtrauma and insufficient recovery from chronic repetitive use and overloads, which impair the tendon’s intrinsic healing response. Clinically, it presents as localized pain, swelling, and reduced mobility. However, diagnosis is limited to the later stages of the condition, when macro-scale damage is already detectable and the tendon is widely degenerated. Despite its high prevalence, the damage mechanisms that initiate chronic tendon degeneration remain poorly understood.

Tendon’s function derives from its multi-scale hierarchical organization that enables force transmission, fatigue resistance, and viscoelastic behavior. While prior work has identified candidate structural damage mechanisms, the direct link between these initiating mechanisms and in vivo tendon mechanical impairment is lacking. Repetitive loading, insufficient recovery, and the tendon’s limited intrinsic healing capacity due to hypovascularity leave the tissue prone to injury and disrupt its innate remodeling processes. Although tendinopathy is widely regarded as a degenerative condition, emerging evidence viindicates that inflammation plays an important role in the early stages of tendon injury. This dissertation assesses in vivo mechanics alongside tendon multi-scale structure and remodeling responses during the early stages of tendon overload injury.

To accomplish this, an in vivo loading system was used to deliver noninvasive, controlled loads to the rat Achilles tendon through passive cyclic ankle dorsiflexion. We first established an acute, physiologically relevant overload injury model and characterized the tendon’s acute healing response across repeated overload bouts. We next assessed how loading magnitude shapes tendon response and recovery, combining quantitative imaging and gene expression with in vivo mechanical measurements to resolve the relationship between joint- and tendon-level responses under repetitive load and limited recovery. Finally, we linked multi-scale structural changes to in vivo mechanical function during the early days following injuries.

Together, this body of work identifies early structural and biological responses to repetitive acute tendon overload in a physiologically relevant context. By linking in vivo tendon function to its multi-scale structure during the earliest stages of injury, this work advances understanding of what initiates tendon dysfunction and provides a foundation for earlier clinical intervention and diagnosis.