Spontaneous rupture of the Achilles tendon is increasingly common in the middle aged population. However, the cause for the particularly high incidence of injury in this age group is not well understood. Therefore, the objective of this study was to identify age-specific differences in the Achilles tendon-muscle complex using an animal model. Functional measures were performed in vivo and tissues were harvested following euthanasia for mechanical, structural, and histological analysis from young, middle aged, and old rats. Numerous alterations in tendon properties were detected across age groups, including inferior material properties (maximum stress, modulus) with increasing age. Differences in function were also observed, as older animals exhibited increased ankle joint passive stiffness and decreased propulsion force during locomotion. Macroscale differences in tendon organization were not observed, although cell density and nuclear shape did vary between age groups. Muscle fiber size and type distribution were not notably affected by age, indicating that other factors may be more responsible for age-specific Achilles tendon rupture rates. This study improves our understanding of the role of aging in Achilles tendon biomechanics and ankle function, and helps provide a potential explanation for the disparate incidence of Achilles tendon ruptures in varying age groups.

Conservative treatment (non-operative) of Achilles tendon ruptures is suggested to produce equivalent capacity for return to function; however, long term results and the role of return to activity (RTA) for this treatment paradigm remain unclear. Therefore, the objective of this study was to evaluate the long term response of conservatively treated Achilles tendons in rodents with varied RTA. Sprague Dawley rats (n=32) received unilateral blunt transection of the Achilles tendon followed by randomization into groups that returned to activity after 1-week (RTA1) or 3-weeks (RTA3) of limb casting in plantarflexion, before being sacrificed at 16-weeks post-injury. Uninjured age-matched control animals were used as a control group (N=10). Limb function, passive joint mechanics, tendon properties (mechanical, histological), and muscle properties (histological, immunohistochemical) were evaluated. Results showed that although hindlimb ground reaction forces and range of motion returned to baseline levels by 16-weeks regardless of RTA, ankle stiffness remained altered. RTA1 and RTA3 groups both exhibited no differences in fatigue properties; however, the secant modulus, hysteresis, and laxity were inferior compared to uninjured age-matched control tendons. Despite these changes, tendons 16-weeks post-injury achieved secant stiffness levels of uninjured tendons. RTA1 and RTA3 groups had no differences in histological properties, but had higher cell numbers compared to control tendons. No changes in gastrocnemius fiber size or type in the superficial or deep regions were detected, except for type 2× fiber fraction. Together, this work highlights RTA-dependent deficits in limb function and tissue-level properties in long-term Achilles tendon and muscle healing.

The Achilles tendon is frequently injured. Data to support specific treatment strategies for complete and partial tears is inconclusive. Regardless of treatment, patients risk re‐rupture and typically have long‐term functional deficits. We previously showed that pulsed electromagnetic field (PEMF) therapy improved tendon‐to‐bone healing in a rat rotator cuff model. This study investigated the effects of PEMF on rat ankle function and Achilles tendon properties after (i) complete Achilles tendon tear and repair with immobilization, (ii) partial Achilles tendon tear without repair and with immobilization, and (iii) partial Achilles tendon tear without repair and without immobilization. We hypothesized that PEMF would improve tendon properties, increase collagen organization, and improve joint function, regardless of injury type. After surgical injury, animals were assigned to a treatment group: (i) no treatment control, (ii) 1 h of PEMF per day, or (iii) 3 h of PEMF per day. Animals were euthanized at 1, 3, and 6 weeks post‐injury. Joint mechanics and gait analysis were assessed over time, and fatigue testing and histology were performed at each time point. Results indicate no clear differences in Achilles healing with PEMF treatment. Some decreases in tendon mechanical properties and ankle function suggest PEMF may be detrimental after complete tear. Some early improvements were seen with PEMF after partial tear with immobilization; however, immobilization was found to be a confounding factor. This body of work emphasizes the distinct effects of PEMF on tendon‐to‐bone healing and supports trialing potential treatment strategies pre‐clinically across tendons before applying them clinically. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:70–81, 2020

Rotator cuff repair failure remains common due to poor tendon healing, particularly at the enthesis. We previously showed that pulsed electromagnetic field (PEMF) therapy improved the mechanical properties of the rat supraspinatus tendon postoperatively. However, little is known about the mechanisms behind PEMF‐dependent contributions to improved healing in this injury model. The objective of this study was to determine the influence of PEMF treatment on tendon gene expression and cell composition, as well as bone microarchitecture and dynamic bone metabolism during early stages of healing. We hypothesized that PEMF treatment would amplify tendon‐healing related signaling pathways while mitigating inflammation and improve bone metabolism at the repair site. Rats underwent rotator cuff injury and repair followed by assignment to either control (non‐PEMF) or PEMF treatment groups. Gene and protein expression as well as tendon and bone histological assessments were performed 3, 7, 14, 21, and 28 days after injury. Gene expression data demonstrated an upregulation in the bone morphogenetic protein 2 signaling pathway and increases in pro‐osteogenic genes at the insertion, supporting important processes to re‐establish the tendon‐bone interface. PEMF also downregulated genes related to a fibrotic healing response. Anti‐inflammatory effects were demonstrated by both gene expression and macrophage phenotype. PEMF significantly increased the rate of kinetic bone formation directly adjacent to the tendon enthesis as well as the number of cuboidal surface osteoblasts (active osteoblasts) in the humeral head. This study has provided insight into how PEMF affects cellular and molecular processes in the supraspinatus tendon and adjacent bone after injury and repair.

The high prevalence of tendon retear following rotator cuff repair motivates the development of new therapeutics to promote improved tendon healing. Controlled delivery of non-steroidal anti-inflammatory drugs to the repair site via an implanted scaffold is a promising option for modulating inflammation in the healing environment. Furthermore, biodegradable nanofibrous delivery systems offer an optimized architecture and surface area for cellular attachment, proliferation, and infiltration while releasing soluble factors to promote tendon regeneration. To this end, we developed a bilayer delivery system (BiLDS) for localized and controlled release of ibuprofen (IBP) to temporally mitigate inflammation and enhance tendon remodeling following surgical repair by promoting organized tissue formation. In vitro evaluation confirmed the delayed and sustained release of IBP from Labrafil-modified poly(lactic-co-glycolic) acid microspheres within sintered poly(ε-caprolactone) electrospun scaffolds. Biocompatibility of the BiLDS was demonstrated with primary Achilles tendon cells in vitro. Implantation of the IBP-releasing BiLDS at the repair site in a rat rotator cuff injury and repair model led to decreased expression of proinflammatory cytokine, tumor necrotic factor-α, and increased anti-inflammatory cytokine, transforming growth factor-β1. The BiLDS remained intact for mechanical reinforcement and recovered the tendon structural properties by 8 weeks. These results suggest the therapeutic potential of a novel biocompatible nanofibrous BiLDS for localized and tailored delivery of IBP to mitigate tendon inflammation and improve repair outcomes. Future studies are required to define the mechanical implications of an optimized BiLDS in a rat model beyond 8 weeks or in a larger animal model.