Therapeutic potential of mesenchymal stem cells to treat Achilles tendon injuries

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An experimental study of low-level laser therapy in rat Achilles tendon injury

The aim of this controlled animal study was to investigate the effect of low-level laser therapy (LLLT) administered 30 min after injury to the Achilles tendon. The study animals comprised 16 Sprague Dawley male rats divided in two groups. The right Achilles tendons were injured by blunt trauma using a mini guillotine, and were treated with LLLT or placebo LLLT 30 min later. The injury and LLLT procedures were then repeated 15 hours later on the same tendon. One group received active LLLT (lambda = 904 nm, 60 mW mean output power, 0.158 W/cm(2) for 50 s, energy 3 J) and the other group received placebo LLLT 23 hours after LLLT. Ultrasonographic images were taken to measure the thickness of the right and left Achilles tendons. Animals were then killed, and all Achilles tendons were tested for ultimate tensile strength (UTS). All analyses were performed by blinded observers. There was a significant increase in tendon thickness in the active LLLT group when compared with the placebo group (p < 0.05) and there were no significant differences between the placebo and uninjured left tendons. There were no significant differences in UTS between laser-treated, placebo-treated and uninjured tendons. Laser irradiation of the Achilles tendon at 0.158 W/cm(2) for 50 s (3 J) administered within the first 30 min after blunt trauma, and repeated after 15 h, appears to lead to edema of the tendon measured 23 hours after LLLT. The guillotine blunt trauma model seems suitable for inflicting tendon injury and measuring the effects of treatment on edema by ultrasonography and UTS. More studies are needed to further refine this model.

Twelve-month outcomes following surgical repair of the achilles tendon

IntroductionIncidence of Achilles tendon rupture (ATR) has increased over recent years, and debate regarding optimal management has been widely documented. Most papers have focused on surgical success, complications and short term region-specific outcomes. Inconsistent use of standardised outcome measures following surgical ATR repair has made it difficult to evaluate the impact of ATR on a patient’s health status post-surgery, and to compare this to other injury types. This study aimed to report the frequency of surgical repairs of the Achilles tendon over a five-year period within an orthopaedic trauma registry, and to investigate return to work (RTW) status, health status and functional outcomes at 12 months post-surgical repair of the Achilles tendon.MethodsTwo hundred and four adults registered by the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) who underwent surgical repair of the Achilles tendon between July 2009 and June 2014 were included in this prospective cohort study. The Extended Glasgow Outcome Scale (GOS-E), 3-level European Quality of Life 5 Dimension measure (EQ-5D-3L), and RTW status 12 months following surgical ATR repair were collected through structured telephone interviews conducted by trained interviewers.ResultsAt 12 months, 92% of patients were successfully followed up. Of those working prior to injury, 95% had returned to work. 42% of patients reported a full recovery on the GOS-E scale. The prevalence of problems on the EQ-5D–3 L at 12 months was 0.5% for self-care, 11% for anxiety, 13% for mobility, 16% for activity, and 22% for pain. 16% of patients reported problems with more than one domain. The number of surgical repairs of the Achilles tendon within the VOTOR registry decreased by 68% over the five-year study period.ConclusionsOverall, patients recover well following surgical repair of the Achilles tendon. However, in this study, deficits in function persisted for over half of patients at 12 months post-injury. The decreased incidence of surgical Achilles tendon repair may reflect a change in practice at VOTOR hospitals whereby surgery may be becoming less favoured for initial ATR management.

The acute adaptations of normal and pathological human Achilles tendons to eccentric and concentric exercise

Eccentric exercise is the conservative treatment of choice for mid-portion Achilles tendinopathy. While there is a growing body of evidence supporting the medium to long term efficacy of eccentric exercise in Achilles tendinopathy treatment, very few studies have investigated the short term response of the tendon to eccentric exercise. Moreover, the mechanisms through which tendinopathy symptom resolution occurs remain to be established. The primary purpose of this thesis was to investigate the acute adaptations of the Achilles tendon to, and the biomechanical characteristics of, the eccentric exercise protocol used for Achilles tendinopathy rehabilitation and a concentric equivalent. The research was conducted with an orientation towards exploring potential mechanisms through which eccentric exercise may bring about a resolution of tendinopathy symptoms. Specifically, the morphology of tendinopathic and normal Achilles tendons was monitored using high resolution sonography prior to and following eccentric and concentric exercise, to facilitate comparison between the treatment of choice and a similar alternative. To date, the only proposed mechanism through which eccentric exercise is thought to result in symptom resolution is the increased variability in motor output force observed during eccentric exercise. This thesis expanded upon prior work by investigating the variability in motor output force recorded during eccentric and concentric exercises, when performed at two different knee joint angles, by limbs with and without symptomatic tendinopathy. The methodological phase of the research focused on establishing the reliability of measures of tendon thickness, tendon echogenicity, electromyography (EMG) of the Triceps Surae and the standard deviation (SD) and power spectral density (PSD) of the vertical ground reaction force (VGRF). These analyses facilitated comparison between the error in the measurements and experimental differences identified as statistically significant, so that the importance and meaning of the experimental differences could be established. One potential limitation of monitoring the morphological response of the Achilles tendon to exercise loading is that the Achilles tendon is continually exposed to additional loading as participants complete the walking required to carry out their necessary daily tasks. The specific purpose of the last experiment in the methodological phase was to evaluate the effect of incidental walking activity on Achilles tendon morphology. The results of this study indicated that walking activity could decrease Achilles tendon thickness (negative diametral strain) and that the decrease in thickness was dependent on both the amount of walking completed and the proximity of walking activity to the sonographic examination. Thus, incidental walking activity was identified as a potentially confounding factor for future experiments which endeavoured to monitor changes in tendon thickness with exercise loading. In the experimental phase of this thesis the thickness of Achilles tendons was monitored prior to and following isolated eccentric and concentric exercise. The initial pilot study demonstrated that eccentric exercise resulted in a greater acute decrease in Achilles tendon thickness (greater diametral strain) compared to an equivalent concentric exercise, in participants with no history of Achilles tendon pain. This experiment was then expanded to incorporate participants with unilateral Achilles tendinopathy. The major finding of this experiment was that the acute decrease in Achilles tendon thickness observed following eccentric exercise was modified by the presence of tendinopathy, with a smaller decrease (less diametral strain) noted for tendinopathic compared to healthy control tendon. Based on in vitro evidence a decrease in tendon thickness is believed to reflect extrusion of fluid from the tendon with loading. This process would appear to be limited by the presence of pathology and is hypothesised to be a result of the changes in tendon structure associated with tendinopathy. Load induced fluid movement may be important to the maintenance of tendon homeostasis and structure as it has the potential to enhance molecular movement and stimulate tendon remodelling. On this basis eccentric exercise may be more beneficial to the tendon than concentric exercise. Finally, EMG and motor output force variability (SD and PSD of VGRF) were investigated while participants with and without tendinopathy performed the eccentric and concentric exercises. Although between condition differences were identified as statistically significant for a number of force variability parameters, the differences were not greater than the limits of agreement for repeated measures. Consequently the meaning and importance of these findings were questioned. Interestingly, the EMG amplitude of all three Triceps Surae muscles did not vary with knee joint angle during the performance of eccentric exercise. This raises questions pertaining to the functional importance of performing the eccentric exercise protocol at each of the two knee joint angles as it is currently prescribed. EMG amplitude was significantly greater during concentric compared to eccentric muscle actions. Differences in the muscle activation patterns may result in different stress distributions within the tendon and be related to the different diametral strain responses observed for eccentric and concentric muscle actions.

Achilles tendinopathy has an aberrant strain response to eccentric exercise

Purpose: Eccentric exercise has become the treatment of choice for Achilles tendinopathy. However, little is known about the acute response of tendons to eccentric exercise or the mechanisms underlying its clinical benefit. This research evaluated the sonographic characteristics and acute anteroposterior (AP) strain response of control (healthy), asymptomatic, and symptomatic Achilles tendons to eccentric exercise. Methods: Eleven male adults with unilateral midportion Achilles tendinopathy and nine control male adults without tendinopathy participated in the research. Sagittal sonograms of the Achilles tendon were acquired immediately before and after completion of a common eccentric rehabilitation exercise protocol and again 24 h later. Tendon thickness, echogenicity, and AP strain were determined 40 mm proximal to the calcaneal insertion. Results: Compared with the control tendon, both the asymptomatic and symptomatic tendons were thicker (P < 0.05) and hypoechoic (P < 0.05) at baseline. All tendons decreased in thickness immediately after eccentric exercise (P < 0.05). The symptomatic tendon was characterized by a significantly lower AP strain response to eccentric exercise compared with both the asymptomatic and control tendons (P < 0.05). AP strains did not differ in the control and asymptomatic tendons. For all tendons, preexercise thickness was restored 24 h after exercise completion. Conclusions: These observations support the concept that Achilles tendinopathy is a bilateral or systemic process and structural changes associated with symptomatic tendinopathy alter fluid movement within the tendon matrix. Altered fluid movement may disrupt remodeling and homeostatic processes and represents a plausible mechanism underlying the progression of tendinopathy.

The effect of exercise repetition on the frequency characteristics of motor output force : Implications for Achilles tendinopathy rehabilitation

Objectives: To investigate the frequency characteristics of the ground reaction force (GRF) recorded throughout the eccentric Achilles tendon rehabilitation programme described by Alfredson. Design: Controlled laboratory study, longitudinal. Methods: Nine healthy adult males performed six sets (15 repetitions per set) of eccentric ankle exercise. Ground reaction force was recorded throughout the exercise protocol. For each exercise repetition the frequency power spectrum of the resultant ground reaction force was calculated and normalised to total power. The magnitude of peak relative power within the 8-12 Hz bandwidth and the frequency at which this peak occurred was determined. Results: The magnitude of peak relative power within the 8-12 Hz bandwidth increased with each successive exercise set and following the 4th set (60 repetitions) of exercise the frequency at which peak relative power occurred shifted from 9 to 10 Hz. Conclusions: The increase in magnitude and frequency of ground reaction force vibrations with an increasing number of exercise repetitions is likely connected to changes in muscle activation with fatigue and tendon conditioning. This research illustrates the potential for the number of exercise repetitions performed to influence the tendons' mechanical environment, with implications for tendon remodelling and the clinical efficacy of eccentric rehabilitation programmes for Achilles tendinopathy.

Measuring mechanical properties of tendon in vivo

Introduction: Understanding the mechanical properties of tendon is an important step to guiding the process of improving athletic performance, predicting injury and treating tendinopathies. The speed of sound in a medium is governed by the bulk modulus and density for fluids and isotropic materials. However, for tendon,which is a structural composite of fluid and collagen, there is some anisotropy requiring an adjustment for Poisson’s ratio. In this paper, these relationships are explored and modelled using data collected, in vivo, on human Achilles tendon. Estimates for elastic modulus and hysteresis based on speed of sound data are then compared against published values from in vitro mechanical tests. Methods: Measurements using clinical ultrasound imaging, inverse dynamics and acoustic transmission techniques were used to determine dimensions, loading conditions and longitudinal speed of sound for the Achilles tendon during a series of isometric plantar flexion exercises against body weight. Upper and lower bounds for speed of sound versus tensile stress in the tendon were then modelled and estimates derived for elastic modulus and hysteresis. Results: Axial speed of sound varied between 1850 to 2090 m.s−1 with a non-linear, asymptotic dependency on the level of tensile stress in the tendon 5–35 MPa. Estimates derived for the elastic modulus ranged between 1–2 GPa. Hysteresis derived from models of the stress-strain relationship, ranged from 3–11%. These values agree closely with those previously reported from direct measurements obtained via in vitro mechanical tensile tests on major weight bearing tendons. Discussion: There is sufficiently good agreement between these indirect (speed of sound derived) and direct (mechanical tensile test derived) measures of tendon mechanical properties to validate the use of this non-invasive acoustic transmission technique. This non-invasive method is suitable for monitoring changes in tendon properties as predictors of athletic performance, injury or therapeutic progression.

The acute transverse strain response of the patellar tendon to quadriceps exercise

Introduction: The human patellar tendon is highly adaptive to changes in habitual loading but little is known about its acute mechanical response to exercise. This research evaluated the immediate transverse strain response of the patellar tendon to a bout of resistive quadriceps exercise. Methods: Twelve healthy adult males (mean age 34.0+/-12.1 years, height 1.75+/-0.09 m and weight 76.7+/-12.3 kg) free of knee pain participated in the research. A 10-5 MHz linear-array transducer was used to acquire standardised sagittal sonograms of the right patellar tendon immediately prior to and following 90 repetitions of a double-leg parallel-squat exercise performed against a resistance of 175% bodyweight. Tendon thickness was determined 20-mm distal to the pole of the patellar and transverse Hencky strain was calculated as the natural log of the ratio of post- to pre-exercise tendon thickness and expressed as a percentage. Measures of tendon echotexture (echogenicity and entropy) were also calculated from subsequent gray-scale profiles. Results: Quadriceps exercise resulted in an immediate decrease in patellar tendon thickness (P<.05), equating to a transverse strain of -22.5+/-3.4%, and was accompanied by increased tendon echogenicity (P<.05) and decreased entropy (P<.05). The transverse strain response of the patellar tendon was significantly correlated with both tendon echogenicity (r = -0.58, P<.05) and entropy following exercise (r=0.73, P<.05), while older age was associated with greater entropy of the patellar tendon prior to exercise (r=0.79, P<.05) and a reduced transverse strain response (r=0.61, P<.05) following exercise. Conclusions: This study is the first to show that quadriceps exercise invokes structural alignment and fluid movement within the matrix that are manifest by changes in echotexture and transverse strain in the patellar tendon., (C)2012The American College of Sports Medicine

The acute response of tendon to loading: implications for rehabilitation

Achilles tendinopathy is a common disorder involving physically active and sedentary individuals alike. Although the processes underlying its development are poorly understood, tendinopathy is widely regarded as an ‘overuse’ injury in which the tendon fails to adapt to prevalent loading conditions. Paradoxically, there is emerging evidence that heavy eccentric loading of the Achilles tendon may be an effective conservative approach for treatment of tendinopathy, with success rates of 60–80% reported. Interestingly, loading exercises involving other forms of muscle action, such as concentric activation, have been shown to be less effective treatment options. However, little is known about the acute response of tendon to exercise at present, and there are few plausible explanatory mechanisms for the observed beneficial effects of eccentric exercise, as opposed to other forms of strain stimuli. This paper presents the findings from a series of experiments undertaken to evaluate the effect of various strain stimuli on the time-dependent response of human Achilles tendon in vivo. It was shown for the first time, that heavy resistive ankle plantarflexion/ dorsiflexion exercises induced an immediate and significant decrease in Achilles tendon thickness (~15%). While thickness returned to pre-exercise levels within 24 hours, the recovery was exponential, with primary recovery occurring in less than 6 hours post-exercise. We proposed that such a diametral strain response with tensile loading reflects collagen realignment, Poison’s effects and radial extrusion of water from the tendon core. With unloading, the recovery of tendon dimensions likely reflects the re-diffusion of water via osmotic and/or inflammatory driven processes. Interestingly, prolonged walking was found to induce a similar diametral strain response. In subsequent studies, we demonstrated that eccentric exercise resulted in a greater reduction (-21%) in Achilles tendon thickness than isolated concentric exercise alone (-5%), despite a similar loading impulse. These novel findings, coupled with observations of a reduced diametral strain response with tendon pathology, highlight the importance of fluid movement to tendon function, nutrition and health. They also provide new insights into potential mechanisms underlying Achilles tendinopathy that impact rehabilitation strategies.

Non-invasive clinical measurement of the viscoelastic properties of tendon using acoustic wave transmission

Background. In isotropic materials, the speed of acoustic wave propagation is governed by the bulk modulus and density. For tendon, which is a structural composite of fluid and collagen, however, there is some anisotropy requiring an adjustment for Poisson's ratio. This paper explores these relationships using data collected, in vivo, on human Achilles tendon and then compares estimates of elastic modulus and hysteresis against published values from in vitro mechanical tests. Methods. Measurements using conventional B-model ultrasound imaging, inverse dynamics and acoustic transmission techniques were used to determine dimensions, loading conditions and longitudinal speed of sound in the Achilles tendon during a series of isometric plantar flexion exercises against body weight. Upper and lower bounds for speed of sound versus tensile stress in the tendon were then modelled and estimates of the elastic modulus and hysteresis of the Achilles tendon derived. Results. Axial speed of sound varied between 1850 and 2090 ms-1 with a non-linear, asymptotic dependency on the level of tensile stress (5-35 MPa) in the tendon. Estimates derived for the elastic modulus of the Achilles tendon ranged between 1-2 GPa. Hysteresis derived from models of the stress-strain relationship, ranged from 3-11%. Discussion. Estimates of elastic modulus agree closely with those previously reported from direct measurements obtained via mechanical tensile tests on major weight bearing tendons in vitro [1,2]. Hysteresis derived from models of the stress-strain relationship is consistent with direct measures from various mamalian tendon (7-10%) but is lower than previous estimates in human tendon (17-26%) [3]. This non-invasive method would appear suitable for monitoring changes in tendon properties during dynamic sporting activities.

Fiabilité et changement minimal détectable de mesures obtenues à partir d'images enregistrées par ultrasonographie afin de caractériser l'intégrité du tendon d'Achille

Problématique : La quantification de l’intégrité du tendon d’Achille (TA) représente un défi en réadaptation. L’adoption de mesures quantitatives du TA, extraites à partir d’une image ultrasonographique (QUS), pourrait remédier à cette lacune. Objectifs : 1) Évaluer la fiabilité test-retest et la précision de mesures QUS du TA; 2) Déterminer le meilleur protocole de collecte de mesures QUS à employer en pratique clinique. Méthodologie : Un total de 23 TAs présentant des symptômes d’une tendinopathie achilléenne et 63 TAs asymptomatiques ont été évalués. Pour chaque TA, 8 images ont été enregistrées (2 visites * 2 évaluatrices * 2 images). Différents types de mesures QUS ont été prises : géométriques (épaisseur, largeur, aire), dérivées d’un histogramme des niveaux de gris et dérivées d’une matrice de co-occurrence. Une étude de généralisabilité a quantifié la fiabilité et la précision de chaque mesure QUS et une étude de décision a fait ressortir les meilleurs protocoles de prise de mesures. Résultats : Les mesures géométriques ont démontré une excellente fiabilité et précision. Les mesures dérivées de l’histogramme des niveaux de gris ont démontré une fiabilité et précision médiocres. Les mesures dérivées d’une matrice de co-occurrence ont démontré une fiabilité modérée à excellente et une précision variable. En pratique clinique, il est recommandé de moyenner les résultats de trois images collectées par un évaluateur lors d’une visite. Conclusion : L’utilisation des mesures QUS géométriques permet de quantifier l’intégrité du TA (clinique et recherche). Davantage d’études sur les mesures QUS dérivées d’une matrice de co-occurrence s’avèrent nécessaires.

Effects of low-level laser therapy and eccentric exercises in the treatment of recreational athletes with chronic achilles tendinopathy

Background: Eccentric exercises (EEs) are recommended for the treatment of Achilles tendinopathy, but the clinical effect from EE has a slow onset. Hypothesis: The addition of low-level laser therapy (LLLT) to EE may cause more rapid clinical improvement. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 52 recreational athletes with chronic Achilles tendinopathy symptoms were randomized to groups receiving either EE + LLLT or EE + placebo LLLT over 8 weeks in a blinded manner. Low-level laser therapy (lambda = 820 nm) was administered in 12 sessions by irradiating 6 points along the Achilles tendon with a power density of 60 mW/cm(2) and a total dose of 5.4 J per session. Results: The results of the intention-to-treat analysis for the primary outcome, pain intensity during physical activity on the 100-mm visual analog scale, were significantly lower in the LLLT group than in the placebo LLLT group, with 53.6 mm versus 71.5 mm (P = .0003) at 4 weeks, 37.3 mm versus 62.8 mm (P = .0002) at 8 weeks, and 33.0 mm versus 53.0 mm (P =.007) at 12 weeks after randomization. Secondary outcomes of morning stiffness, active dorsiflexion, palpation tenderness, and crepitation showed the same pattern in favor of the LLLT group. Conclusion: Low-level laser therapy, with the parameters used in this study, accelerates clinical recovery from chronic Achilles tendinopathy when added to an EE regimen. For the LLLT group, the results at 4 weeks were similar to the placebo LLLT group results after 12 weeks.

Achilles tendinopathy

Achilles tendon injury (tendinopathy) and pain occur in active individuals, when the tendon is subject to high or unusual load. Achilles tendinopathy can be resistant to treatment, and symptoms may persist despite both conservative and surgical intervention. The pathology of overuse tendinopathy is non-inflammatory, with a degenerative or failed healing tendon response. The diagnosis of Achilles tendinopathy requires excellent differential diagnosis and an understanding of the role of tendon imaging. Conservative treatment must include exercise, with a bias to eccentric contractions. Surgical treatment is effective after complete tendon rupture, but may not assist recovery from overuse tendinopathy. Further research into the clinical aspects of Achilles tendinopathy is required.