The vasculature and its role in the damaged and healing tendon

Tendon pathology has many manifestations, from spontaneous rupture to chronic tendinitis or tendinosis; the etiology and pathology of each are very different, and poorly understood. Tendon is a comparatively poorly vascularised tissue that relies heavily upon synovial fluid diffusion to provide nutrition. During tendon injury, as with damage to any tissue, there is a requirement for cell infiltration from the blood system to provide the necessary reparative factors for tissue healing. We describe in this review the response of the vasculature to tendon damage in a number of forms, and how and when the revascularisation or neovascularisation process occurs. We also include a section on the revascularisation of tendon during its use as a tendon graft in both ligament reconstruction and tendon–tendon grafting.     

Comparison of ultrasonographic and intraoperative findings in Achilles tendon rupture

The purpose of the study was to assess the value of ultrasonography in the diagnosis of Achilles tendon rupture, by comparing initial ultrasonographic scans and direct intraoperative findings, as well as to follow up the healing process in operatively and conservatively treated patients. Ultrasound examination was performed in 100 patients (91 males and 9 females, with mean age of 46 years) with clinically suspicious Achilles tendon ruptures. Ultrasonographic findings were compared with intraoperative findings. Eighty-eight patients underwent surgery and twelve patients were treated conservatively. Complete ruptures were diagnosed by ultrasound in 88 patients, and partial ruptures in 12 patients. The length of the tendon (Pearson r = 0.973, p < 0.001, Spearman p = 0.972, p < 0.001) and the size of the rupture (Pearson r = 0.940, p < 0.001, Spearman p = 0.905, p < 0.001) measured before surgery by ultrasound and directly during surgery showed a high correlation. Out of 88 operatively treated patients, 86 had a complete rupture and two had a partial rupture. All patients were examined 3, 5, 8, and 12 weeks after injury or after surgery. In the first five weeks, there were statistically significant differences noted between these two groups. Operatively treated tendons healed more quickly, but after eight and twelve weeks this difference had disappeared. Our study showed that ultrasound is an excellent imaging method for confirming the clinical diagnosis of Achilles tendon rupture as well as for following up the process of tendon healing.     

Value of exact focusing of extracorporeal shock waves (ESWT) in therapy of tendinitis calcarea. A prospective randomized study]

A controlled randomized study was designed to analyse the effect of extracorporeal shockwave therapy (ESWT) focussed on either the calcified region or the insertion of the supraspinatus tendon. The study included 50 patients who were treated with a Storz Minilith SI-1 prototype shockwave generator. In the treated group, 4000 impulses (ED+ 0.78 ml/mm2) were applied, under local anaesthesia to the insertion of the supraspinatus in 2 treatment sessions. Control patients received ESWT focussed on the calcified region. Follow-up examinations were carried out 12 weeks after treatment by an independent observer. We found functional improvement and pain reduction in both groups. Statistical analyses showed significant superiority of ESWT focussed on the calcified region for the parameters constant-score (primary endpoint, p < 0.001) and pain intensity (p = 0.001). For the treatment of calcific tendinitis affecting the supraspinatus, we recommend accurate fluoroscopy-controlled focussing of ESWT on the calcification. Focussing on the calcification rather than on the insertion of the supraspinatus tendon is significantly more effective. On the basis of our results, ESWT requires the use of suitable shockwave generators that permit accurate focussing.     

Plantarflexor fiber and tendon slack length are strong determinates of simulated single-leg heel raise height

Achilles tendon ruptures have been linked with detrimental changes in muscle-tendon structure, which may help explain long-term functional deficits. However, the causal effects of muscle-tendon structure on joint function have not been tested in a controlled setting. Therefore, the purpose of this study was to test the implications of muscle-tendon unit parameters on simulated single-leg heel raise height. We hypothesized that muscle fiber length and resting ankle angle – a clinical surrogate measure of tendon slack length – would predict single-leg heel raise height more strongly than other parameters. To test this hypothesis, we developed a two-part simulation paradigm that recreated clinically relevant muscle-tendon scenarios and then tested these parameters on single-leg heel raise height. We found that longer muscle fibers had the greatest positive effect on single-leg heel raise height. However, tendon slack length, determined by simulating resting ankle angles in a secondary analysis, revealed a stronger negative correlation with heel raise height. Our findings support previous clinical observations that both muscle fascicle length and resting tendon length are important muscle-tendon parameters for patient function. In addition to minimizing tendon elongation following rupture, treatment plans should focus on preserving plantarflexor muscle structure to mitigate functional loses following Achilles tendon ruptures.     

Arterial supply of the human long biceps tendon

The present study deals with the question whether an insufficient vascular supply of certain areas can be made responsible for ruptures in the biceps tendon. The macroscopic and microscopic examination shows that the blood supply of the tendon in the part most prone to ruptures, that is in the bicipital groove, is guaranteed even in older individuals. It is at least much better than in the intra-articular portion where ruptures are seldom observed. This means that mechanical components such as friction are dominant. The vascular factors seem to play a minor part.     

Antibody neutralization of TGF-beta enhances the deterioration of collagen fascicles in a tissue-cultured tendon matrix with ex vivo fibroblast infiltration

A tissue-cultured tendon matrix infiltrated with cultured fibroblasts can be regarded as an ideal tissue-engineered tendon model. To clarify the role of TGF-beta in a tissue-cultured tendon matrix during ex vivo cellular infiltration, the present ex vivo study was conducted to test the following hypothesis that antibody neutralization of TGF-beta enhances weakening of the collagen fascicles of the patellar tendon matrix in response to ex vivo fibroblast infiltration. In skeletally mature female rabbits, fibroblasts were isolated from the right patellar tendons using an explant culture technique, and the left patellar tendons underwent multiple freeze/thaw treatment with liquid nitrogen to obtain an acellular tendon matrix. Each acellular tendon was placed in a collagen gel containing cultured fibroblasts and then incubated with or without anti-TGF-beta1 antibody for 6 weeks. We found that antibody neutralization of TGF-beta enhanced the decrease in the tensile strength and tensile modulus of the collagen fascicles of the patellar tendon matrix in response to ex vivo fibroblast infiltration. The present study indicates a possibility that TGF-beta may have a role in suppressing the material deterioration of the fascicles in the tendon during ex vivo cellular infiltration.     

Relevant sonographic parameters of a painful shoulder in symptomatic dialyzed patients versus asymptomatic dialyzed and healthy volunteers

The aim of this study is to find dialysis relevant sonographic parameters of painful shoulder of the symptomatic dialyzed patients comparing them with parameters in asymptomatic dialyzed patients and healthy volunteers. Significant difference in all metric parameters (thickness of supraspinatus tendon, diameter of biceps tendon sheet and capsula-bone distance) were noticed between all groups and the symptomatic had the highest values. Asymptomatic had the higher values then volunteers. Inhomogenicity of the tendon and biceps tendon sheet effusion in the symptomatic patients were the most often occurred. Subdeltoid effusion, deposits and tendon rupture were found only in symptomatic patients. No difference in presence of calcifications between symptomatic and asymptomatic was found. Metric parameters are relevant and associated with dialysis, as well as biceps tendon effusion tendon inhomogenicity, deposits and subdeltoid effusion. Tendon ruptures are relatively rare and nonspecific.     

Association between matrix metalloproteinase-3 polymorphism and anterior cruciate ligament ruptures

Anterior cruciate ligament (ACL) ruptures are considered to be the most severe joint injury in sports. However, the precise etiologies of ACL injuries are not fully understood. Recently, the gene encoding the matrix metalloproteinase-3 (MMP-3, stromelysin-1) was shown to be associated with anterior cruciate ligament ruptures. The 5A/6A polymorphism in the promoter of the MMP-3 gene affects the regulation of MMP-3 gene expression. We examined the association between polymorphism within -1612 of the MMP-3 gene and ACL rupture in an independent population. Eighty-six participants between 20 and 40 years of age with surgically diagnosed ACL ruptures and 100 healthy controls between 18 and 28 years of age without history of ligament or tendon injuries were recruited for the study. All participants were genotyped for the MMP-3 polymorphism (-1612 5A/6A). Statistical analyses of genotype frequencies between patients and healthy controls were performed by the chi-square test. A significant difference was found between ACL rupture subgroups in terms of genotype association (5A+ (5A/5A, 5A/6A): 37.5% in contact sports vs 20% in non-contact sports; P = 0.02). In allelic association, there were significant differences (6A: 81.2% in contact sports vs 89.1% in non-contact sports, 5A: 18.8% in contact sports vs 10.9% in non-contact sports, P = 0.01). The 5A+ genotype of MMP-3 was represented in ACL ruptures in contact sport participants. We propose that this sequence variant is a specific genetic element that should be included in a multifactorial model to understand the etiologies and risk factors for ACL rupture.     

The mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells

Tendinitis and tendon rupture during treatment with fluoroquinolone antibiotics is thought to be mediated via oxidative stress. This study investigated whether ciprofloxacin and moxifloxacin cause oxidative stress and mitochondrial damage in cultured normal human Achilles’ tendon cells and whether an antioxidant targeted to mitochondria (MitoQ) would protect against such damage better than a non-mitochondria targeted antioxidant. Human tendon cells from normal Achilles’ tendons were exposed to 0–0.3 mm antibiotic for 24 h and 7 days in the presence of 1 µm MitoQ or an untargeted form, idebenone. Both moxifloxacin and ciprofloxacin resulted in up to a 3-fold increase in the rate of oxidation of dichlorodihydrofluorescein, a marker of general oxidative stress in tenocytes (p<0.0001) and loss of mitochondrial membrane permeability (p<0.001). In cells treated with MitoQ the oxidative stress was less and mitochondrial membrane potential was maintained. Mitochondrial damage to tenocytes during fluoroquinolone treatment may be involved in tendinitis and tendon rupture.     

Collagen fibril size and crimp morphology in ruptured and intact Achilles tendons.

The present study examined the hypothesis that collagen fibril diameter and crimp angle in ruptured human Achilles tendons differed from that of intact ones. Tissue samples were obtained from the central core (distal core) and the posterior periphery (distal superficial) at the rupture site, and the proximally intact (proximal superficial) part of the tendon in 10 subjects (38+/-8 years) with a complete tendon rupture. For comparisons corresponding tissue samples were procured from age (38+/-7 years) and gender matched intact Achilles tendons during routine forensic autopsy. The cross-sectional area density and diameter distribution of fibrils were analyzed using stereological techniques of digitized electron microscopy biopsy cross-sections, while crimp angle was measured by the changing banding pattern of collagen fibers when rotated between crossed polars. Nine of 10 persons with tendon ruptures reported that the injury did not occur during exceedingly large forces, and none experienced any symptoms in the days or months prior to the injury. Fibril diameter distribution showed no region-specific differences in either the ruptured or intact tendons for either group. However, in the distal core there were fewer fibrils in the ruptured compared to the intact tendons in 60-150 nm range, P<0.01. Similarly, in the distal superficial portion there were fewer fibrils in the ruptured compared to the intact tendons in the 90-120 nm range, 2P<0.05, while there were no differences in the proximal superficial tendons. Crimp angle did not display any region-specific differences, or any difference between the rupture and intact tendons. In conclusion, these data suggest that although crimp morphology is unchanged there appears to be a site-specific loss of larger fibrils in the core and periphery of the Achilles tendon rupture site. Moreover, the lack of symptoms prior to the rupture suggests that clinical tendinopathy is not an etiological factor in complete tendon ruptures.     

Extrinsic cell infiltration and revascularization accelerate mechanical deterioration of the patellar tendon after fibroblast necrosis

This study was performed to determine the contribution of extrinsic cell infiltration and revascularization into the patellar tendon in alteration of the mechanical properties of the patellar tendon after intrinsic fibroblast necrosis using 77 rabbits. In Group I, after the patellar tendon underwent the in situ freeze-thaw treatment, a wrapping treatment was performed to inhibit any extrinsic cell infiltration into the tendon. In Group II, the patellar tendon underwent the freeze-thaw treatment without any of the wrapping treatment. In Group III, the patellar tendon underwent the same wrapping treatment but without any freeze-thaw treatment. The cell culture study demonstrated that the in situ freeze-thaw treatment killed from 97 to 100 percent of the cells in the patellar tendon. Histologically, no cells were found in the midsubstance of the patellar tendon in Group I at 1, 3, and 6 weeks. In Group II, a number of cells and some vessels were found scattered in the tendon at 3 and 6 weeks. Mechanically, the elastic modulus and the tensile strength of the patellar tendon of Group II were significantly lower than those of Groups I and III at 3 and 6 weeks. These facts suggest that extrinsic cell infiltration and revascularization from the surrounding tissues accelerate the deterioration of the mechanical properties of the patellar tendon matrix after intrinsic fibroblast necrosis.     

Screening Method Based on Walking Plantar Impulse for Detecting Musculoskeletal Senescence and Injury

No consensus has been reached on how musculoskeletal system injuries or aging can be explained by a walking plantar impulse. We standardize the plantar impulse by defining a principal axis of plantar impulse. Based upon this standardized plantar impulse, two indexes are presented: plantar pressure record time series and plantar-impulse distribution along the principal axis of plantar impulse. These indexes are applied to analyze the plantar impulse collected by plantar pressure plates from three sources: Achilles tendon ruptures; elderly people (ages 62–71); and young people (ages 19–23). Our findings reveal that plantar impulse distribution curves for Achilles tendon ruptures change irregularly with subjects’ walking speed changes. When comparing distribution curves of the young, we see a significant difference in the elderly subjects’ phalanges plantar pressure record time series. This verifies our hypothesis that a plantar impulse can function as a means to assess and evaluate musculoskeletal system injuries and aging.     

The influence of concentric and eccentric loading on the finger pulley system

In this study we investigated the influence of the loading condition (concentric vs. eccentric loading) on the pulley system of the finger. For this purpose 39 cadaver finger (14 hands, 10 donors) were fixed into an isokinetic loading device. The forces in the flexor tendons and at the fingertip were recorded. In the concentric loading condition A2 and A4 ruptures as well as alternative events such as fracture of a phalanx or avulsion of the flexor tendons were almost equally distributed, whereas the A2 pulley rupture was the most common event (59%) in the eccentric loading condition and alternative events were rare (23.5%). The forces in the deep flexor tendon, the fingertip and in the pulleys were significantly lower in the eccentric loading condition. As the ruptures occurred at lower loads in the eccentric than in the concentric loading condition it can be concluded that friction may be an advantage for climbers, supporting the holding force of their flexor muscles but may also increase the susceptibility to injury.     

Free-flap coverage of the exposed Achilles tendon

Posterior skin loss of the distal lower leg enhances the risk of exposure of the Achilles tendon. Most commonly, these wounds are a sequela to peripheral vascular insufficiency or else posttraumatic in origin. As a consequence, local flaps or skin grafts frequently are inadequate options for achieving coverage. Free-tissue transfers have proven to be a reasonable alternative in these situations for preservation of tendon function or even limb salvage. In this series of 12 patients, small defects were best covered with fasciocutaneous flaps, whereas the larger and usually chronic, concomitantly suppurating wounds required muscle flaps. Eighty-three percent (10 of 12) of patients remained ambulatory with healed wounds, obviating the need for extremity amputation.     

Impact of taping after finger flexor tendon pulley ruptures in rock climbers

Flexor tendon pulley ruptures are the most common injury in rock climbers. Therapeutic standards usually include a prolonged use of taping applied as a replacement for the lost pulley in a circular fashion at the base of the proximal phalanx. Our biomechanical considerations, however, suggest a new taping method, the H-tape. The purpose of the study is to evaluate whether this new taping method can effectively change the course of the flexor tendon and therefore reduce the tendon-bone distance. In order to compare the effects of different taping methods described in the literature with the newly developed taping method, we performed standardized ultrasound examinations of 8 subjects with singular A2 pulley rupture and multiple pulley ruptures of A2 and A3 pulleys and determined the respective tendon-bone distance for the different taping methods, versus without tape at a preset position on the proximal phalanx. In a second approach, we evaluated the effect of the new taping method on the strength of the injured finger using a force platform on 12 subjects with different pulley ruptures with injuries older than 1 year. The new taping method decreased the tendon-bone distance in the injured finger significantly by 16%, whereas the other taping methods did not. The strength development was significantly better with the new tape for the crimp grip position (+13%), but there was no significant improvement for the hanging position. We recommend taping with the newly presented taping technique after pulley rupture.     

Aspirin inhibits adipogenesis of tendon stem cells and lipids accumulation in rat injury tendon through regulating PTEN/PI3K/AKT signalling

Tendon injury repairs are big challenges in sports medicine, and fatty infiltration after tendon injury is very common and hampers tendon injury healing process. Tendon stem cells (TSCs), as precursors of tendon cells, have shown promising effect on injury tendon repair for their tenogenesis and tendon extracellular matrix formation. Adipocytes and lipids accumulation is a landmark event in pathological process of tendon injury, and this may induce tendon rupture in clinical practice. Based on this, it is important to inhibit TSCs adipogenesis and lipids infiltration to restore structure and function of injury tendon. Aspirin, as the representative of non‐steroidal anti‐inflammatory drugs (NSAIDs), has been widely used in tendon injury for its anti‐inflammatory and analgesic actions, but effect of aspirin on TSCs adipogenesis and fatty infiltration is still unclear. Under adipogenesis conditions, TSCs were treated with concentration gradient of aspirin. Oil red O staining was performed to observe changes of lipids accumulation. Next, we used RNA sequencing to compare profile changes of gene expression between induction group and aspirin‐treated group. Then, we verified the effect of filtrated signalling on TSCs adipogenesis. At last, we established rat tendon injury model and compared changes of biomechanical properties after aspirin treatment. The results showed that aspirin decreased lipids accumulation in injury tendon and inhibited TSCs adipogenesis. RNA sequencing filtrated PTEN/PI3K/AKT signalling as our target. After adding the signalling activators of VO‐Ohpic and IGF‐1, inhibited adipogenesis of TSCs was reversed. Still, aspirin promoted maximum loading, ultimate stress and breaking elongation of injury tendon. In conclusion, by down‐regulating PTEN/PI3K/AKT signalling, aspirin inhibited adipogenesis of TSCs and fatty infiltration in injury tendon, promoted biomechanical properties and decreased rupture risk of injury tendon. All these provided new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy.     

Toronto scientists using wire mould to treat malignant melanomas of the choroid

The quadriceps tendon and patellar ligament rupture rarely, even when under great stress or trauma, but can rupture spontaneously in patients with chronic diseases such as gout, rheumatoid arthritis and renal disease. Several factors probably combine to weaken the tendon, including an impoverished local vascular supply, repeated microtrauma and secondary hypoparathyroidism with osteodystrophy. In the three cases reported here, one of which was bilateral, the patients were being treated for chronic renal disease; surgical repair of the tendons led to sound healing and a return to normal function of the joints.