Hydrogen peroxide induced tendinopathic changes in a rat model of patellar tendon injury

Tendinopathy includes cases with chronic tendon pain and spontaneous tendon ruptures, which is putatively resulted from failed tendon healing. Overuse is a major risk factor of tendinopathy, which can impose mechanical and oxidative stress to tendons. Previous studies investigated the influences of mechanical stress, but the direct impact of oxidative stress on tendon healing remains unclear. We hypothesized that imposed oxidative stress can impair tendon healing and lead to tendinopathic changes. Thirty-nine rats were operated for patellar tendon window injury. From weeks 3-5 post-operation, the rats received three weekly subcutaneous injections of saline, 50 or 500 μM H₂ O₂ (n = 13) over patellar tendon. Gait analysis for pain assessment and 3D ultrasound imaging for detection of tendinopathic changes were performed at pre-injury and 6-week post-operation. At week 6, knee specimens were harvested for histology or tensile mechanical test. Elastic modulus of the healing patellar tendons was significantly lower in 50 μM but not 500 μM H₂ O₂ group, while ultimate mechanical stress was not significantly different across groups. Similarly, only the 50 μM H₂ O₂ group exhibited pain-associated gait asymmetry. Significant tendon swelling with increased tendon volume was observed in the 50 μM H₂ O₂ group. There were hypoechogenic changes in the tendon wound, but there was no significant difference in percentage vascularity. H₂ O₂ impaired tendon healing and elicited tendinopathic changes, with respect to pain and structural abnormalities. Oxidative stress plays a role in the failed tendon healing of tendinopathies, and H₂ O₂ -induced failed tendon healing may serve as a good animal model to study tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3268-3274, 2018.