Postinjury biomechanics of Achilles tendon vary by sex and hormone status

Abstract

Achilles tendon ruptures are common injuries. Sex differences are present in mechanical properties of uninjured Achilles tendon, but it remains unknown if these differences extend to tendon healing. We hypothesized that ovariectomized females (OVX) and males would exhibit inferior postinjury tendon properties compared with females. Male, female, and OVX Sprague-Dawley rats (n = 32/group) underwent acclimation and treadmill training before blunt transection of the Achilles tendon midsubstance. Injured hindlimbs were immobilized for 1 wk, followed by gradual return to activity and assessment of active and passive hindlimb function. Animals were euthanized at 3 or 6 wk postinjury to assess tendon structure, mechanics, and composition. Passive ankle stiffness and range of motion were superior in females at 3 wk; however, by 6 wk, passive and active function were similar in males and females but remained inferior in OVX. At 6 wk, female tendons had greater normalized secant modulus, viscoelastic behavior, and laxity compared with males. Normalized secant modulus, cross-sectional area and tendon glycosaminoglycan composition were inferior in OVX compared with females at 6 wk. Total fatigue cycles until tendon failure were similar among groups. Postinjury muscle fiber size was better preserved in females compared with males, and females had greater collagen III at the tendon injury site compared with males at 6 wk. Despite male and female Achilles tendons withstanding similar durations of fatigue loading, early passive hindlimb function and tendon mechanical properties, including secant modulus, suggest superior healing in females. Ovarian hormone loss was associated with inferior Achilles tendon healing.

Aging leads to inferior Achilles tendon mechanics and altered ankle function in rodents

“…Animals (n=12–16/group) were acclimated to an instrumented walkway, and spatial, temporal, and kinetic parameters were quantified during autonomous locomotion as previously described (Fryhofer et al, 2016). Briefly, maximum ground reaction forces (medial/lateral, braking, propulsion, vertical) were calculated following isolation of the hindlimb on either one of two six degree-of-freedom force plates and reported as percent of animal body weight (%BW).…”

Mechanical, histological, and functional properties remain inferior in conservatively treated Achilles tendons in rodents: Long term evaluation

“…We used an established animal model of Achilles tendon transection and post-injury hind limb immobilization (Freedman et al, 2016a; Freedman et al, 2016b; Fryhofer et al, 2016) to carefully control the activity paradigm of animals for longitudinal functional and tissue-level follow-up. As most studies examining long-term follow-up in Achilles tendon healing have been completed in humans, this work provides fundamental insight into the tissue-level mechanical and histological changes that exist following injury.…”

“…Ground reaction forces and temporal patterns for the right hind limb were used to evaluate active limb function prior to surgery, and at 4-, 6-, 10-, and 16-weeks post-injury (Freedman et al, 2016a; Freedman et al, 2016b; Fryhofer et al, 2016). Briefly, animals ambulated across an instrumented walkway containing load/torque cells and a camera, and all animals were acclimated four times prior to formal data collection.…”

“…Full-length images of SAF-O stained tendon sections were obtained by stitching of several smaller images (FOV: 2.14 × 1.61mm) and were evaluated for GAG intensity (1, blue; 2, light red; 3, light to dark red). Additionally, the gastrocnemius/soleus muscle complex was harvested, sectioned axially (10 μm), and stained for antibodies against laminin (L9393, Sigma Aldrich) and myosin heavy chain (MyHC) types 1, 2a, and 2b (type 1: BA-D5; type 2a: SC-71; type 2b: BF-F3), as described (Fryhofer et al, 2016; Pardes et al, 2016). The anti-MyHC antibodies were obtained from the Developmental Studies Hybridoma Bank, created by the National Institute of Child Health and Development of the National Institutes of Health (Schiaffino, S; University of Iowa, Department of Biology; Iowa City, IA).…”

Tendon Healing: Mechanical Loading, Microdamage and Gene Expression

“…On the other hand, studies on humans has shown that women's response to exercise in Achilles tendons is differently compared to men, and might reduce their ability to adapt to exercise (7). Additionally, female rats seem to improve their mechanical properties faster in healing Achilles tendons compared to males and ovariectomized females (24). We have only studied female rats and that might be a limitation of our findings, as there seems to be a difference between genders.…”