Healthy Tendon Research Articles

Three‐dimensional morphology and volume of the free Achilles tendon at rest and under load in people with unilateral mid‐portion Achilles tendinopathy

What is the central question of this study? The aim was to determine the effect of mid-portion Achilles tendinopathy (MAT) on free Achilles tendon three-dimensional morphology and volume at rest and under load in people with unilateral MAT. What is the main finding and its importance? Tendinopathic tendon had a larger resting tendon cross-sectional area and anteroposterior diameter relative to healthy tendon. When loaded, tendinopathic tendon experienced a reduction in transverse morphology (i.e. cross-sectional area, anteroposterior and mediolateral diameters) and overall volume reduction. In contrast, the healthy tendon remained isovolumetric and bulged along the anteroposterior axis. These findings suggest a fundamental reorganization of tendinopathic tendon matrix components and altered tendon fluid content when under load. Mid-portion Achilles tendinopathy (MAT) adversely affects free Achilles tendon (AT) structure and composition. However, it is not known how these pathological alterations associated with MAT change the normal three-dimensional (3-D) morphology of free AT at rest and under load throughout the entire free tendon length. Here, we used 3-D ultrasound to examine the effect of unilateral MAT on free tendon 3-D morphology [length, cross-sectional area (CSA), anteroposterior (AP) diameter and mediolateral (ML) diameter] and volume at rest and during a submaximal (50%) voluntary isometric plantarflexion contraction bilaterally in individuals with unilateral MAT (n=10) compared with a matched healthy control group (n=10). The tendinopathic free AT had a greater CSA relative to the control tendons along the entire tendon length, which was mainly driven by a greater tendon AP diameter. Under load, the tendinopathic tendon experienced greater longitudinal and transverse strains than the control tendons. In contrast to the control tendons, which experienced a reduction in tendon CSA and ML diameter, bulged along the AP axis and behaved isovolumetrically under load, the tendinopathic tendon experienced a reduction in tendon CSA, AP diameter and ML diameter and an overall volume reduction. Overall, these findings suggest that the magnitude of longitudinal strain and volume change and the corresponding magnitude and direction of transverse strain under load are altered in MAT compared with normal tendon. These findings are indicative of a fundamental reorganization of the tendon matrix and alterations in tendon fluid content and distribution under load in tendinopathic tendon.

Bevacizumab Improves Achilles Tendon Repair in a Rat Model

Background/Aims: Effective wound-healing generally requires efficient re-vascularization after injury, ensuring sufficient supply with oxygen, nutrients, and various cell populations. While this applies to most tissues, tendons are mostly avascular in nature and harbor relatively few cells, probably contributing to their poor regenerative capacity. Considering the minimal vascularization of healthy tendons, we hypothesize that controlling angiogenesis in early tendon healing is beneficial for repair tissue quality and function. Methods: To address this hypothesis, Bevacizumab, a monoclonal antibody blocking VEGF-A signaling, was locally injected into the defect area of a complete tenotomy in rat Achilles tendon. At 28 days post-surgery, the defect region was investigated using immunohistochemistry against vascular and lymphatic epitopes. Polarization microscopy and biomechanical testing was used to determine tendon integrity and gait analysis for functional testing in treated vs non-treated animals. Results: Angiogenesis was found to be significantly reduced in the Bevacizumab treated repair tissue, accompanied by significantly reduced cross sectional area, improved matrix organization, increased stiffness and Young’s modulus, maximum load and stress. Further, we observed an improved gait pattern when compared to the vehicle injected control group. Conclusion: Based on the results of this study we propose that reducing angiogenesis after tendon injury can improve tendon repair, potentially representing a novel treatment-option.

The Achilles Tendon in Healthy Subjects: An Anthropometric and Ultrasound Mapping Study

Ultrasonography is an inexpensive, fast, and reliable imaging technique widely used to assess the Achilles tendon. Although significant data exists regarding pathologic tendon changes, ultrasound data from healthy individuals are more limited. We aimed to better characterize ultrasound Achilles tendon measurements in healthy individuals and identify important correlating factors. The information collected included patient demographics, body habitus, activity level, foot dominance, and resting ankle angle. Ultrasound analysis was performed bilaterally on the Achilles tendons of 50 subjects using a high-frequency transducer to measure tendon width, thickness, cross-sectional area, and length. Males had a significantly larger mean tendon length, width, thickness, and cross-sectional area. No statistically significant difference was found in any tendon dimension between the white and black participants. Similarly, no difference was found in any tendon parameter when comparing right versus left leg dominance. Healthy subjects had a mean ankle resting angle of 45.1° ± 24° with no statistically significant difference between right and left ankles. Considering all individuals, each tendon parameter (tendon length, width, thickness, and cross-sectional area) correlated positively with subject height, weight, tibia length, and foot size. Only the Achilles cross-sectional area correlated significantly with the activity level. The resting angle of the ankle correlated positively with both tendon length and thickness. In conclusion, we found significant variations in Achilles tendon anatomy in the healthy adult population. We have thoroughly characterized significant correlations between healthy tendon dimensions and various body habitus, activity levels, and ankle parameters. Greater knowledge of the normal Achilles tendon anatomy and characterization of its variations in the healthy population will potentially allow for better pathologic diagnosis and surgical repair.

Cytokines in tendon disease: A Systematic Review.

ObjectivesEmerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified.MethodsWe performed a systematic review of the literature using MEDLINE (U.S. National Library of Medicine, Bethesda, Maryland) in March 2017. Studies reporting the expression of interleukins (ILs), tumour necrosis factor alpha (TNF-α) and interferon gamma in diseased human tendon tissues, and animal models of tendon injury or exercise in comparison with healthy control tissues were included.ResultsIL-1β, IL-6, IL-10, and TNF-α are the cytokines that have been most frequently investigated. In clinical samples of tendinopathy and tendon tears, the expression of TNF-α tended not to change but IL-6 increased in tears. Healthy human tendons showed increased IL-6 expression after exercise; however, IL-10 remained unchanged. Animal tendon injury models showed that IL-1β, IL-6, and TNF-α tend to increase from the early phase of tendon healing. In animal exercise studies, IL-1β expression showed a tendency to increase at the early stage after exercise, but IL-10 expression remained unchanged with exercise.ConclusionsThis review highlights the roles of IL-1β, IL-6, IL-10, and TNF-α in the development of tendon disease, during tendon healing, and in response to exercise. However, there is evidence accumulating that suggests that other cytokines are also contributing to tendon inflammatory processes. Further work with hypothesis-free methods is warranted in order to identify the key cytokines, with subsequent mechanistic and interaction studies to elucidate their roles in tendon disease development.Cite this article: W. Morita, S. G. Dakin, S. J. B. Snelling, A. J. Carr. Cytokines in tendon disease: A Systematic Review. Bone Joint Res 2017;6:656–664. DOI: 10.1302/2046-3758.612.BJR-2017-0112.R1.

Chronic inflammation is a feature of Achilles tendinopathy and rupture

BackgroundRecent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified the importance of inflammation in the development and progression of tendon disease. These...

Beneficial effects of resistance training on the protein profile of the calcaneal tendon during aging

The calcaneal tendon (CT) is the most commonly injured tendon in the human body. Moreover, with advancing age, the amount of damage increases further. Resistance training (RT) could be used to minimize such damages. The aim of the present study was to obtain the identification, detailed protein cataloging and biochemical characterization based on the effects of the aging process and the RT in CT of rats. The analysis by liquid chromatography tandem-mass spectrometry showed 142 distinct proteins, however, only 29 proteins met the inclusion criteria and were analyzed. Aging causes a reduction in the abundance of seven proteins related to extracellular matrix organization, biological regulation and cellular processes. However, RT promoted the positive regulation of proteins important for the maintenance of healthy tendons: seven proteins in young trained and two in older trained group. This study contributes to a better understanding of molecular aspects of the tendon. The down regulation of proteins linked to mechanical function and extracellular matrix remodeling of the tendon during aging can contribute to the increase of injury and weakness in the tendon. Nevertheless, RT proved to be a tool to prevent these adverse effects during aging by increasing proteins involved in the functionality of the tendon.

Calf Muscle Atrophy and Achilles Tendon Elongation After Acute Achilles Tendon Rupture

Calf muscle atrophy and Achilles tendon elongation seems to be the principal structural explanations for calf muscle strength deficit at short and long term follow up and also explain surgery related greater plantar flexion strength compared conservative treatment after acute Achilles tendon rupture. Despite good clinical results of surgery and conservative treatment for acute Achilles tendon rupture (ATR), surgery may result in 10-18% better calf muscle strength. However, 12-18% strength deficit compared to the unaffected leg usually remains even in long-term follow up. We aimed to assess whether Achilles tendon elongation and calf muscle volume changes could explain the difference in calf muscle strength between conservative treatment and surgery and side-to side strength deficit of calf muscle for patients with operatively treated ATR in long term follow-up. Group 1; 60 patients with acute ATRs were randomized to surgery or conservative treatment. Conservative treatment and post operative treatments were identical; cast immobilization for one week, followed by functional orthosis for 6 weeks, which allowed full weight bearing after week 1 and active plantar flexion after week 5 post injury. At 18 months, MRI was used to evaluate the volume of calf muscles and the length of the affected Achilles tendon. Group 2; 60 patients with acute ATRs were randomized to simple end-to-end repair or augmented repair, both with postoperative bracing allowing free active plantar flexion for 3 weeks. After follow-up of =13 years, 55 patients (28 non-augmented, 27 augmented) were re-examined and MRI was used to evaluate the volume of calf muscles, and the length of the Achilles tendons for both legs. Group 1; At 18 months, the mean differences between healthy and affected soleus muscle volumes were 83.2 cm3 (17.7%) after surgery and 115.5 cm3 (24.8%) after conservative treatments (difference between means: 33.1 cm3, 95% CI: 1.3 to 65.0, p = 0.042). Achilles tendon length from calcaneal insertion to soleus muscle MTJ for affected leg was 18.7mm longer for conservative treatment compared operative treatment (95% CI: 8.5 to 28.8, p<0.001). All patients in group 1 suffered up to 21% calf muscle atrophy for affected leg, which was compensated by 11% hypertrophy in flexor hallucis longus (FHL) (p=0.001 in all). Group 2; At 14 years patients in group 2 suffered up to 12% calf muscle atrophy for affected leg which was compensated by 5.4% hypertrophy in flexor halluces longus (FHL) (p=0.001 in all). Achilles tendon length from calcaneal insertion to medial gastrocnemius muscle MTJ for affected leg was 12.1mm longer compared healthy tendon (95% CI, 8.6 to 15.6, p<0.001). At 18 months ATR conservative treatment with a functional rehabilitation protocol resulted in greater soleus muscle atrophy and 19 mm longer calcaneus to soleus MTJ length to surgical treatment. At 14 years ATR operative treatment resulted up to 12% calf muscle atrophy and 12mm longer Achilles tendon of the affected leg. Calf muscle atrophy in the affected leg was compensated with hypertrophy of the FHL both in short and long term follow-up. Achilles tendon elongation may be the principal structural explanation of calf muscle atrophy and muscle strength deficit at short and long term follow-up after ATR.

Increased 15-PGDH expression leads to dysregulated resolution responses in stromal cells from patients with chronic tendinopathy

The mechanisms underpinning the failure of inflammation to resolve in diseased musculoskeletal soft tissues are unknown. Herein, we studied bioactive lipid mediator (LM) profiles of tendon-derived stromal cells isolated from healthy donors and patients with chronic tendinopathy. Interleukin(IL)-1β treatment markedly induced prostaglandin biosynthesis in diseased compared to healthy tendon cells, and up regulated the formation of several pro-resolving mediators including 15-epi-LXA4 and MaR1. Incubation of IL-1β stimulated healthy tendon cells with 15-epi-LXA4 or MaR1 down-regulated PGE2 and PGD2 production. When these mediators were incubated with diseased cells, we only found a modest down regulation in prostanoid concentrations, whereas it led to significant decreases in IL-6 and Podoplanin expression. In diseased tendon cells, we also found increased 15-Prostaglandin Dehydrogenase (15-PGDH) expression as well as increased concentrations of both 15-epi-LXA4 and MaR1 further metabolites, 15-oxo-LXA4 and 14-oxo-MaR1. Inhibition of 15-PGDH using either indomethacin or SW033291 significantly reduced the further conversion of 15-epi-LXA4 and MaR1 and regulated expression of IL-6, PDPN and STAT-1. Taken together these results suggest that chronic inflammation in musculoskeletal soft tissues may result from dysregulated LM-SPM production, and that inhibition of 15-PGDH activity together with promoting resolution using SPM represents a novel therapeutic strategy to resolve chronic tendon inflammation.

Decorin and biglycan are necessary for maintaining collagen fibril structure, fiber realignment, and mechanical properties of mature tendons

The small leucine-rich proteoglycans (SLRPs), decorin and biglycan, are key regulators of collagen fibril and matrix assembly. The goal of this work was to elucidate the roles of decorin and biglycan in tendon homeostasis. Our central hypothesis is that decorin and biglycan expression in the mature tendon would be critical for the maintenance of the structural and mechanical properties of healthy tendons. Defining the function(s) of these SLRPs in tendon homeostasis requires that effects in the mature tendon be isolated from their influence on development. Thus, we generated an inducible knockout mouse model that permits genetic ablation of decorin and biglycan expression in the mature tendon, while maintaining normal expression during development. Decorin and biglycan expression were knocked out in the mature patellar tendon with the subsequent turnover of endogenous SLRPs deposited prior to induction. The acute absence of SLRP expression was associated with changes in fibril structure with a general shift to larger diameter fibrils in the compound knockout tendons, together with fibril diameter heterogeneity. In addition, tendon mechanical properties were altered. Compared to wild-type controls, acute ablation of both genes resulted in failure of the tendon at lower loads, decreased stiffness, a trend towards decreased dynamic modulus, as well as a significant increase in percent relaxation and tissue viscosity. Collagen fiber realignment was also increased with a delayed and slower in response to load in the absence of expression. These structural and functional changes in response to an acute loss of decorin and biglycan expression in the mature tendon demonstrate a significant role for these SLRPs in adult tendon homeostasis.

Promoter methylation status of the TIMP2 and ADAMTS4 genes and patellar tendinopathy

ObjectivesPatellar tendinopathy (PT) is a debilitating and prevalent condition that tends to affect those who are physically active or engaged in jumping sports. Although tendinopathies are known to have a genetic basis, the role of DNA methylation as an epigenetic factor and risk determinant for human PT has never been described.We sought to determine whether differences existed between the methylation profiles of both the TIMP2 and ADAMTS4 gene promoter sequences in a cohort of males having undergone surgery for patellar tendinopathy compared to controls. DesignCase-control epigenetic study using DNA from 10 males with PT and 10 males with healthy tendons. MethodsWe used PCR and targeted pyrosequencing to interrogate the methylation profiles of CpG sites upstream of both the TIMP2 (4 sites) and ADAMTS4 (6 sites) genes. We compared methylation differences between the two groups using t-tests. ResultsWe report no significant (p>0.05) methylation differences within the TIMP2 gene promoter between the PT group and controls across the 4 CpG sites investigated. In contrast, we detected a significant (p=0.016) difference in the methylation status of 1 CpG site, approximately 3kb upstream of the ADAMTS4 gene between the PT group and controls. ConclusionsTo our knowledge, this is the first study to investigate how DNA methylation impacts on the risk of human tendinopathy. Our data indicate that the methylation status of the ADAMTS4 gene is altered in patellar tendinopathy and we speculate on how this change might modify the patellar tendon extra-cellular matrix environment.

Test-retest reliability of echo intensity parameters in healthy Achilles tendons using a semi-automatic tracing procedure.

To evaluate the test-retest reliability of the ultrasound echo intensity parameters on healthy Achilles tendon using a semi-automatic tracing procedure. Eighteen healthy volunteers participated. B-mode images were acquired in the transverse plane (mid-tendon; insertion) and used to analyze tendon echogenicity. Grayscale distribution of the pixels within the selected ROIs was represented as a histogram. Descriptive statistics of the grayscale distribution (mean, variance, skewness, kurtosis, and entropy) and parameters from the co-occurrence matrix (contrast, energy, and homogeneity) were calculated. Reliability of echo intensity parameters of the mid-Achilles tendon ranged from high to very high with an ICC2.k of 0.94 for echogenicity, 0.87 for variance, 0.80 for skewness, 0.72 for kurtosis, 0.89 for entropy, 0.90 for contrast, 0.91 for energy, and 0.93 for homogeneity, while for tendon insertion they ranged from moderate to high with an ICC2.k of 0.74 for echogenicity, 0.88 for variance, 0.75 for skewness, 0.55 for kurtosis, 0.87 for entropy, 0.70 for contrast, 0.77 for energy, and 0.56 for homogeneity. Ultrasound echo intensity is a reliable technique to characterize the internal structure of the Achilles tendon.

* Meltblown Polymer Fabrics as Candidate Scaffolds for Rotator Cuff Tendon Tissue Engineering.

Various biomaterial technologies are promising for tissue engineering, including electrospinning, but commercial scale-up of throughput is difficult. The goal of the study was to evaluate meltblown fabrics as candidate scaffolds for rotator cuff tendon tissue engineering. Meltblown poly(lactic acid) fabrics were produced with several polymer crystallinities and airflow velocities [500(low), 900(medium) or 1400(high) m3air/h/m fabric]. Fiber diameter, alignment, and baseline bidirectional tensile mechanical properties were evaluated. Attachment and spreading of human adipose-derived stem cells (hASCs) were evaluated over 3 days immediately following seeding. After initial screening, the fabric with the greatest Young's modulus and yield stress was selected for 28-day in vitro culture and for evaluation of tendon-like extracellular matrix production and development of mechanical properties. As expected, airflow velocity of the polymer during meltblowing demonstrated an inverse relationship with fiber diameter. All fabrics exhibited fiber alignment parallel to the direction of collector rotation. All fabrics demonstrated mechanical anisotropy at baseline. Cells attached, proliferated, and spread on all fabrics over the initial three-day culture period. Consistent with the observed loss of integrity of the unseeded biomaterial, hASC-seeded scaffolds demonstrated a significant decrease in Young's modulus over 28 days of culture. However, dsDNA, sulfated glycosaminoglycan, and collagen content increased significantly over 28 days. Histology and polarized light microscopy demonstrated collagen deposition and alignment throughout the thickness of the scaffolds. While fiber diameters approximated an order of magnitude greater than those previously reported for electrospun scaffolds intended for tendon tissue engineering, they were still within the range of collagen fiber diameters found in healthy tendon. The extent of matrix production and alignment was similar to that previously observed for multilayered electrospun scaffolds. While the Young's modulus of scaffolds after 28 days of culture was lower than native rotator cuff tendon, it approximated that reported previously following culture of electrospun scaffolds and was on the same order of magnitude as of current Food and Drug Administration-approved patches for rotator cuff augmentation. Together, these data suggest that with minor polymer and parameter modifications, meltblown scaffolds could provide an economical, high-throughput production alternative method to electrospinning for use in rotator cuff tendon tissue engineering.

Achilles Tendon Penetration for Continuous 810 nm and Superpulsed 904 nm Lasers Before and After Ice Application: An In Situ Study on Healthy Young Adults.

There is a lack of knowledge about the influence tissue temperature may have on laser light penetration and tendon structure. The purpose of this study was to investigate whether penetration of laser energy in human Achilles tendons differed before and after ice pack application. The Achilles tendons (n = 54) from 27 healthy young adults were irradiated with two class 3B lasers (810 nm 200 mW continuous mode laser and a 904 nm 60 mW superpulsed mode laser). The optical energy penetrating the Achilles area was measured before and after 20 min of ice application. Measurements were obtained after 30, 60, and 120 sec irradiation with the 904 nm laser and after 30 and 60 sec irradiation with the 810 nm laser. Achilles tendon thickness was measured with ultrasonography. Optical energy penetration increased significantly (p < 0.01) after ice application for both lasers and at all time points from 0.34% to 0.39% of energy before ice application to 0.43-0.52% of energy after ice application for the 904 nm laser and from 0.24% to 0.25% of energy before ice application to 0.30-0.31% of energy after ice application for the 810 nm laser. The energy loss per centimeter of irradiated tissue was significantly higher (p < 0.05) at all time points after ice application. Ultrasonography imaging of skin-to-skin and transversal tendon thickness was significantly reduced after ice application at p = 0.05 and p = 0.03, respectively. Achilles tendon thickness in the longitudinal plane remained unchanged (p = 0.49). The penetration of laser light increased significantly through healthy Achilles tendons subjected to 20 min of cooling. These findings occurred in the presence of a significant reduction in skin temperature and Achilles tendon thickness.

Tendon healing induced by chemically modified mRNAs.

Tendon disorders are frequent both in human and veterinary medicine with high re-injury rates and unsatisfactory therapeutic treatments. Application of naked, chemically-modified mRNA (cmRNA), encoding for therapeutic proteins, is an innovative approach to address tendon healing. In the current study, we demonstrated that injection of naked cmRNA, diluted in a glucose-containing solution, into tendons resulted in high protein expression in healthy and experimentally-injured tendons. Injection of bone morphogenetic protein 7 (BMP-7)-encoding cmRNA resulted in a significantly higher expression of BMP-7 protein and reduced formation of collagen type III, compared to vehicle control. Moreover, in a large animal model, reporter protein expression was detectable not only in healthy, but also in experimentally-injured, severely inflamed tendons. Summarising, these results demonstrated the potential of cmRNAs encoding for therapeutic proteins as a new class of drugs for the treatment of tendon disorders.

Differential expression of alarmins—S100A9, IL-33, HMGB1 and HIF-1α in supraspinatus tendinopathy before and after treatment

BackgroundAlarmins, endogenous molecules released on tissue damage have been shown to play an important role in inflammatory musculoskeletal conditions including fracture repair andrheumatoid arthritis. However, the contribution of alarmins to...

A report on the accessory head of Flexor Pollicis Longus and Variations of Forearm Musculature

Abstract Introduction: Gantzer's muscle has drawn attention from several authors owing to the possibility of interosseous nerve compression. This is a report of an accessory head of flexor pollicis longus (FPL, a variant of Gantzer's muscle) and a review of the variations of all muscles of the forearm. Materials and Methods: An accessory head of FPL was discovered in both the right and left antebrachial regions during a cadaver dissection. The muscle was dissected and photographed. Results: The anatomical variation I report is a slender conical muscle joining the FPL. Its origin merged with fibers of the flexor digitorum superficialis. It inserted into the upper part of the middle third of the forearm by joining the medial tendinous part of the FPL; this join was by means of a short cylindrical tendon. The reported muscle was innervated by the anterior interosseous nerve, which was seen to be present posterolateral to the muscle in both forearms. Conclusion: The described muscle might cause pressure problems to the underlying structures especially the anterior interosseous nerve. Variations must be considered during surgical intervention to avoid unintentional damage to healthy tendons. In addition, accessory tendons can potentially be useful in the repair or replacement of damaged tendons through surgical transfer or transplantation. Variations of muscles, especially accessory muscles, may mimic the behavior of soft tissue tumors and can result in nerve compressions. This collection of variations of the forearm musculature will be useful to surgeons in practice as well as students in dissection labs.

Presence of Bacteria in Spontaneous Achilles Tendon Ruptures

Background: The structural pathology of Achilles tendon (AT) ruptures resembles tendinopathy, but the causes remain unknown. Recently, a number of diseases were found to be attributed to bacterial infections, resulting in low-grade inflammation and progressive matrix disturbance. The authors speculate that spontaneous AT ruptures may also be influenced by the presence of bacteria. Hypothesis: Bacteria are present in ruptured ATs but not in healthy tendons. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients with spontaneous AT ruptures and patients undergoing anterior cruciate ligament (ACL) reconstruction were recruited for this study. During AT surgical repair, excised tendinopathic tissue was collected, and healthy tendon samples were obtained as controls from hamstring tendon grafts used in ACL reconstruction. Half of every sample was reserved for DNA extraction and the other half for histology. Polymerase chain reaction (PCR) was conducted using 16S rRNA gene universal primers, and the PCR products were sequenced for the identification of bacterial species. A histological examination was performed to compare tendinopathic changes in the case and control samples. Results: Five of 20 AT rupture samples were positive for the presence of bacterial DNA, while none of the 23 hamstring tendon samples were positive. Sterile operating and experimental conditions and tests on samples, controlling for harvesting and processing procedures, ruled out the chance of postoperative bacterial contamination. The species identified predominantly belonged to the Staphylococcus genus. AT rupture samples exhibited histopathological features characteristic of tendinopathy, and most healthy hamstring tendon samples displayed normal tendon features. There were no apparent differences in histopathology between the bacterial DNA–positive and bacterial DNA–negative AT rupture samples. Conclusion: The authors have demonstrated the presence of bacterial DNA in ruptured AT samples. It may suggest the potential involvement of bacteria in spontaneous AT ruptures.

Treatment Algorithm for Chronic Achilles Tendon LesionsReview of the Literature and Proposal of a New Classification.

Chronic Achilles tendon lesions (CATLs) ensue from a neglected acute rupture or a degenerated tendon. Surgical treatment is usually required. The current English literature (PubMed) about CATLs was revised, and particular emphasis was given to articles depicting CATL classification. The available treatment algorithms are based on defect size. We propose the inclusion of other parameters, such as tendon degeneration, etiology, and time from injury to surgery. Partial lesions affecting less than (I stage) or more than (II stage) half of the tendon should be treated conservatively for healthy tendons, within 12 weeks of injury. In II stage complex cases, an end-to-end anastomosis is required. Complete lesions inferior to 2 cm should be addressed by an end-to-end anastomosis, with a tendon transfer in the case of tendon degeneration. Lesions measuring 2 to 5 cm require a turndown flap and a V-Y tendinous flap in the case of a good-quality tendon; degenerated tendons may require a tendon transfer. Lesions larger than 5 cm should be treated using two tendon transfers and V-Y tendinous flaps. A proper algorithm should be introduced to calibrate the surgical procedures. In addition to tendon defect size, tendon degeneration, etiology of the lesion, and time from injury to surgery are crucial factors that should be considered in the surgical planning.

Quantification of Internal Stress-Strain Fields in Human Tendon: Unraveling the Mechanisms that Underlie Regional Tendon Adaptations and Mal-Adaptations to Mechanical Loading and the Effectiveness of Therapeutic Eccentric Exercise.

By virtue of their anatomical location between muscles and bones, tendons make it possible to transform contractile force to joint rotation and locomotion. However, tendons do not behave as rigid links, but exhibit viscoelastic tensile properties, thereby affecting the length and contractile force in the in-series muscle, but also storing and releasing elastic stain energy as some tendons are stretched and recoiled in a cyclic manner during locomotion. In the late 90s, advancements were made in the application of ultrasound scanning that allowed quantifying the tensile deformability and mechanical properties of human tendons in vivo. Since then, the main principles of the ultrasound-based method have been applied by numerous research groups throughout the world and showed that tendons increase their tensile stiffness in response to exercise training and chronic mechanical loading, in general, by increasing their size and improving their intrinsic material. It is often assumed that these changes occur homogenously, in the entire body of the tendon, but recent findings indicate that the adaptations may in fact take place in some but not all tendon regions. The present review focuses on these regional adaptability features and highlights two paradigms where they are particularly evident: (a) Chronic mechanical loading in healthy tendons, and (b) tendinopathy. In the former loading paradigm, local tendon adaptations indicate that certain regions may “see,” and therefore adapt to, increased levels of stress. In the latter paradigm, local pathological features indicate that certain tendon regions may be “stress-shielded” and degenerate over time. Eccentric exercise protocols have successfully been used in the management of tendinopathy, without much sound understanding of the mechanisms underpinning their effectiveness. For insertional tendinopathy, in particular, it is possible that the effectiveness of a loading/rehabilitation protocol depends on the topography of the stress created by the exercise and is not only reliant upon the type of muscle contraction performed. To better understand the micromechanical behavior and regional adaptability/mal-adaptability of tendon tissue it is important to estimate its internal stress-strain fields. Recent relevant advancements in numerical techniques related to tendon loading are discussed.

Resorbable electrospun polydioxanone fibres modify the behaviour of cells from both healthy and diseased human tendons.

Chronic tendinopathy in an active and ageing population represents an increasing burden to healthcare systems. Rotator cuff tendinopathy alone accounts for approximately 70 % of all shoulder pain. Tendinopathic tissue has a disorganised extracellular matrix, altered vasculature, and infiltration of fibroblasts and inflammatory cells. This altered biology may contribute to the limited success of surgical repair strategies. Electrospun resorbable scaffolds can potentially enhance endogenous repair mechanisms by influencing the tissue microenvironment. Polydioxanone (PDO) has an established safety profile in patients. We compared the response of healthy and diseased human tendon cells to electrospun PDO fibres using live cell imaging, proliferation, flow cytometry, and gene expression studies. Within 4 h of initial contact with electrospun PDO, healthy tendon cells underwent a marked transformation; elongating along the fibres in a fibre density dependent manner. Diseased tendon cells initially responded at a slower rate, but ultimately underwent a similar morphological change. Electrospun fibres increased the proliferation rate of diseased tendon cells and increased the ratio of type I:IIIcollagenmRNA expression. Flow cytometry revealed decreased expression of CD106, a marker of mesenchymal stem cells, and increased expression of CD10 on healthy versus diseased tendon cells. PDO electrospun scaffolds further promoted CD106negCD10pos expression of healthy tendon cells. Despite their behavioural differences, both healthy and diseased human tendon cells responded to electrospun PDO fibres. This encourages further work establishing their efficacy in augmenting surgical repair of diseased tendons.