Early response to tendon fatigue damage accumulation in a novel in vivo model
Introduction
Tendinopathy and tendon rupture are common painful and debilitating clinical problems. The Achilles, patellar and rotator cuff tendons are particularly prone to tendinopathies (Kannus and Jozsa, 1991; Maffulli et al., 2004) due to their tensile overload, material and structural inhomogeneity, and poor healing response (Leadbetter, 1992; Maganaris et al., 2004; Mehta et al., 2003; Riley, 2004). Observed degenerative changes in ruptured tendons suggest pre-rupture damage accumulation (Kannus and Jozsa, 1991; Tallon et al., 2001). Additionally, matrix disorganization with cellular proliferation and lipid accumulation was observed in macroscopically “healthy” tendons from older subjects (Kannus and Jozsa, 1991), suggesting damage accumulation. It is thus thought that cumulative injury from overuse causes degeneration leading to tendon weakening and failure.
Overuse/cyclic loading protocols have been used to investigate the mechanical basis of degradation and matrix degeneration in tendons. Studies evaluating the relationship between applied stress and number of cycles to failure of devitalized tendons and ligaments showed progressive degradation of mechanical properties (Ker et al., 2000; Pike et al., 2000; Schechtman and Bader, 1997, Schechtman and Bader, 2002; Wang and Ker, 1995; Wang et al., 1995; Wren et al., 2003). In vivo tendon modeled overuse injuries by utilizing treadmill running, muscle stimulation and repeated reaching tasks (Backman et al., 1990; Nakama et al., 2005; Soslowsky et al., 2000) and showed tendon damage, including fiber disorganization, microtears, and reduction of modulus and maximum stress. Furthermore, inability of degenerative changes to recover with time (Soslowsky et al., 2000) indicate a poor repair response likely from disrupted collagen fibrillogenesis, which is required for the scar tissue deposition, collagen synthesis, and tissue remodeling seen in wound healing (Hiranuma et al., 1996; Oshiro et al., 2003; Sakai et al., 2001; Williams et al., 1984)). However, the process of microstructural damage initiation and accumulation from loading, and the resulting tendon weakening and cellular-matrix response should be evaluated.
Previously, we investigated fatigue-induced damage accumulation in tendons using an ex vivo model of rat flexor digitorum longus (FDL) tendons (Fung et al., 2008). Results demonstrated changes in morphology and mechanical properties representing key mechanistic events during fatigue life. In this study, we developed an in vivo animal model to evaluate tendon response to fatigue loading at various damage levels based on previous ex vivo studies. For comparison, we concurrently evaluated the response of the patellar tendon to laceration and suture-repair. We hypothesize that fatigue-induced damage in tendons does not elicit the typical healing response seen in laceration. More specifically, while the extent to which a fatigue damage tendon may undergo any structural repair is unknown, we expect that its response to fatigue damage accumulation will differ from that of a lacerated tendon in that it will not exhibit the expression spectrum of collagens that accompanies the lacerated tendon's attempt to undergo structural repair.
Section snippets
Animal model for in vivo fatigue loading
Our criteria for selecting an animal model were (1) a small animal previously used to investigate tendon biomechanics, tissue adaptation, and biochemical and molecular studies of tendon physiology and pathology; (2) a tendon that can be fatigue loaded with control; and (3) a tendon that exhibits tendinopathy in humans. Candidates evaluated included the FDL, Achilles, patellar, supraspinatus and tail tendons in mice, rats, rabbits and dogs.
Patellar tendons in adult female Sprague-Dawley rats (n
Animal model
At completion of the loading protocol, gross inspection of the knee joint and the patellar tendon showed no damage from clamping. Rats resumed normal cage activity with no evidence of lameness or inability to use the loaded limb within 2 h of recovery. At all time points, there was no gross evidence of acute inflammation at the gripping sites or in the tendon. Incision sites showed only normal granulation tissue.
Biomechanics
No tendons failed during the course of fatigue loading. Tendons were loaded for
Discussion
We developed an in vivo model in which rat patellar tendons were fatigue loaded to precisely defined levels of cumulative damage to explore mechanisms of tendon degeneration. Results showed that low level fatigue damage is represented by isolated kinked fiber patterns that transversely span across several fibers. In mid-fatigue life, tendons exhibited a greater density of deformation patterns. Surprisingly at Low- and Mid-levels, tendon damage caused increased stiffness and decreased
Conflict of interest
None of the authors have any relevant commercial relationships which may lead to a conflict of interest.
Acknowledgements
This study was supported by Aircast Foundation and NIH (AR41210, AR44927, AR49967, and AR52743).
References (33)
- et al.
Changes in collagen matrix composition in human posterior tibial tendon dysfunction
Jt. Bone Spine
(2002) - et al.
Comparison of damage accumulation measures in human cortical bone
J. Biomech.
(1997) Cell–matrix response in tendon injury
Clin. Sports Med.
(1992)- et al.
Biomechanics of tendon injury and repair
J. Biomech.
(2004) - et al.
Etiologic and pathogenetic factors for rotator cuff tendinopathy
Clin. Sports Med.
(2003) - et al.
Flexor tendon healing in the rat: a histologic and gene expression study
J. Hand Surg. [Am.]
(2003) - et al.
Type I and type III procollagen gene expressions in the early phase of ligament healing in rabbits: an in situ hybridization study
J. Orthop. Res.
(2001) - et al.
Changes in histoanatomical distribution of types I, III and V collagen promote adaptative remodeling in posterior tibial tendon rupture
Clinics
(2008) - et al.
In vitro fatigue of human tendons
J. Biomech.
(1997) - et al.
Fatigue damage of human tendons
J. Biomech.
(2002)
Laminated tears of the human rotator cuff: a histologic and immunochemical study
J. Shoulder Elbow Surg.
Neer Award 1999. Overuse activity injures the supraspinatus tendon in an animal model: a histologic and biomechanical study
J. Shoulder Elbow Surg.
Healing ligaments have decreased cyclic modulus compared to normal ligaments and immobilization further compromises healing ligament response to cyclic loading
J. Orthop. Res.
Chronic achilles paratenonitis with tendinosis: an experimental model in the rabbit
J. Orthop. Res.
Extracellular matrices in peritendinous connective tissue after surgical injury to the chicken flexor tendon
Arch. Orthop. Trauma Surg.
Cited by (120)
Glycosaminoglycans modulate microscale mechanics and viscoelasticity in fatigue injured tendons
2023, Journal of BiomechanicsDevelopment and application of a novel in vivo overload model of the Achilles tendon in rat
2023, Journal of BiomechanicsReview of human supraspinatus tendon mechanics. Part I: fatigue damage accumulation and failure
2022, Journal of Shoulder and Elbow Surgery