Response Of Tendon Research Articles

Adaptive and innate immune cell responses in tendons and lymph nodes after tendon injury and repair.

Tendon injuries are a common clinical condition with limited treatment options. The cellular components of the innate immune system, such as neutrophils and macrophages, have been studied in tendon injuries. However, the adaptive immune system, comprising specialized lymphocytes, plays an important role in orchestrating the healing of numerous tissues, but less is known about these cells in tendon healing. To gain a greater understanding of the biological processes that regulate tendon healing, we determined how the cellular components of the adaptive and innate immune system respond to a tendon injury using two-month-old male mice. We observed that lymphatic vasculature is present in the epitenon and superficial regions of Achilles tendons, and that the lymphatics drain into the popliteal lymph node. We then created an acute Achilles tenotomy followed by repair, and collected tendons and popliteal lymph nodes 1, 2, and 4 wk after injury. Tendon injury resulted in a robust adaptive immune cell response that followed an initial innate immune cell response in tendons and lymph nodes. Monocytes, neutrophils, and macrophages initially accumulated at 1 wk after injury in tendons, while dendritic cells and CD4+ T cells peaked at 2 wk after injury. B cells and CD8+ T cells progressively increased over time. In parallel, immune cells of the popliteal lymph node demonstrated a similarly coordinated response to the injury. These results suggest that there is an adaptive immune response to tendon injury, and adaptive immune cells may play a role in regulating tendon healing.NEW & NOTEWORTHY While the innate immune system, consisting of macrophages and related hematopoietic cells, has been studied in tendon injury, less is known about the adaptive immune system. Using a mouse model of Achilles tendon tenotomy and repair, we observed an adaptive immune cell response, consisting of CD4+ and CD8+ T cells, and B cells, which occur through 4 wk after tendon injury. This response appeared to be coordinated by the draining popliteal lymph node.

Tendon response to matrix unloading is determined by the patho-physiological niche

Although the molecular mechanisms behind tendon disease remain obscure, aberrant stromal matrix turnover and tissue hypervascularity are known hallmarks of advanced tendinopathy. We harness a tendon explant model to unwind complex cross-talk between the stromal and vascular tissue compartments. We identify the hypervascular tendon niche as a state-switch that gates degenerative matrix remodeling within the tissue stroma. Here pathological conditions resembling hypervascular tendon disease provoke rapid cell-mediated tissue breakdown upon mechanical unloading, in contrast to unloaded tendons that remain functionally stable in physiological low-oxygen/-temperature niches. Analyses of the stromal tissue transcriptome and secretome reveal that a stromal niche with elevated tissue oxygenation and temperature drives a ROS mediated cellular stress response that leads to adoption of an immune-modulatory phenotype within the degrading stromal tissue. Degradomic analysis further reveals a surprisingly rich set of active matrix proteases behind the progressive loss of tissue mechanics. We conclude that the tendon stromal compartment responds to aberrant mechanical unloading in a manner that is highly dependent on the vascular niche, with ROS gating a complex proteolytic breakdown of the functional collagen backbone.

Hydrodynamic performance of a floating offshore OWC wave energy converter: An experimental study

To investigate the dynamic response of a floating moored oscillating water column device under realistic sea states, a focused wave technique was developed in this study to generate user-defined wave trains in a wave basin equipped with a piston-type wavemaker. The experimental setup allowed for simultaneous measurements of the designed focused wave trains, internal chamber wave elevations and air pressure, dynamic tendon response and the model's global motion responses. Based on the experimental results it was found that to accurately replicate the theoretical wave time series, a minimal focal reconstruction of 200 components was required which resulted in a focused wave regeneration accuracy greater than 93% with strong repeatability. The tested model showed typical motion responses to that of generalised tension leg platform systems with significant surge offsets along with stiff heave and pitch motions. Applying vertical tendons to the system allowed for the floating offshore device to be exposed to deeper waters, and hence the larger energy source associated with deep water ocean waves.

Insulin-like growth factor 1 signaling in tenocytes is required for adult tendon growth.

Tenocytes serve to synthesize and maintain collagen fibrils and other extracellular matrix proteins in tendon. Despite the high prevalence of tendon injury, the underlying biologic mechanisms of postnatal tendon growth and repair are not well understood. IGF1 plays an important role in the growth and remodeling of numerous tissues but less is known about IGF1 in tendon. We hypothesized that IGF1 signaling is required for proper tendon growth in response to mechanical loading through regulation of collagen synthesis and cell proliferation. To test this hypothesis, we conditionally deleted the IGF1 receptor (IGF1R) in scleraxis (Scx)-expressing tenocytes using a tamoxifen-inducible Cre-recombinase system and caused tendon growth in adult mice via mechanical overload of the plantaris tendon. Compared with control Scx-expressing IGF1R-positive (Scx:IGF1R+) mice, in which IGF1R is present in tenocytes, mice that lacked IGF1R in their tenocytes [Scx-expressing IGF1R-negative (Scx:IGF1RΔ) mice] demonstrated reduced cell proliferation and smaller tendons in response to mechanical loading. Additionally, we identified that both the PI3K/protein kinase B and ERK pathways are activated downstream of IGF1 and interact in a coordinated manner to regulate cell proliferation and protein synthesis. These studies indicate that IGF1 signaling is required for proper postnatal tendon growth and support the potential use of IGF1 in the treatment of tendon disorders.-Disser, N. P., Sugg, K. B., Talarek, J. R., Sarver, D. C., Rourke, B. J., Mendias, C. L. Insulin-like growth factor 1 signaling in tenocytes is required for adult tendon growth.

Calcaneal Tendon Plasticity Following Gastrocnemius Muscle Injury in Rat.

Cross-talk between skeletal muscle and tendon is important for tissue homeostasis. Whereas the skeletal muscle response to tendon injury has been well-studied, to the best of our knowledge the tendon response to skeletal muscle injury has been neglected. Thus, we investigated calcaneal tendon extracellular matrix (ECM) remodeling after gastrocnemius muscle injury using a rat model. Wistar rats were randomly divided into four groups: control group (C; animals that were not exposed to muscle injury) and harvested at different time points post gastrocnemius muscle injury (3, 14, and 28 days) for gene expression, morphological, and biomechanical analyses. At 3 days post injury, we observed mRNA-level dysregulation of signaling pathways associated with collagen I accompanied with disrupted biomechanical properties. At 14 days post injury, we found reduced collagen content histologically accompanied by invasion of blood vessels into the tendon proper and an abundance of peritendinous sheath cells. Finally, at 28 days post injury, there were signs of recovery at the gene expression level including upregulation of transcription factors related to ECM synthesis, remodeling, and repair. At this time point, tendons also presented with increased peritendinous sheath cells, decreased adipose cells, higher Young’s modulus, and lower strain to failure compared to the uninjured controls and all post injury time points. In summary, we demonstrate that the calcaneal tendon undergoes extensive ECM remodeling in response to gastrocnemius muscle injury leading to altered functional properties in a rat model. Tendon plasticity in response to skeletal muscle injury merits further investigation to understand its physiological relevance and potential clinical implications.

Morphologically bioinspired hierarchical nylon 6,6 electrospun assembly recreating the structure and performance of tendons and ligaments

Reconstructions of ruptured tendons and ligaments currently have dissatisfactory failure rate. Failures are mainly due to the mechanical mismatch of commercial implants with respect to the host tissue. In fact, it is crucial to replicate the morphology (hierarchical in nature) and mechanical response (highly-nonlinear) of natural tendons and ligaments. The aim of this study was to develop morphologically bioinspired hierarchical Nylon 6,6 electrospun assemblies recreating the structure and performance of tendons and ligaments. First, we built different electrospun bundles to find the optimal orientation of the nanofibers. A 2nd-level hierarchical assembly was fabricated with a dedicated process that allowed tightly joining the bundles one next to the other with an electrospun sheath, so as to improve the mechanical performance. Finally, a further hierarchical 3rd-level assembly was constructed by grouping several 2nd-level assemblies. The morphology of the different structures was assessed with scanning electron microscopy and high-resolution X-ray tomography, which allowed measuring the directionality of the nanofibers in the bundles and in the sheaths. The mechanical properties of the single bundles and of the 2nd-level assemblies were measured with tensile tests. The single bundles and the hierarchical assemblies showed morphology and directionality of the nanofibers similar to the tendons and ligaments. The strength and stiffness were comparable to that of tendons and ligaments. In conclusion, this work showed an innovative electrospinning production process to build nanofibrous Nylon 6,6 hierarchical assemblies which are suitable as future implantable devices and able to mimic the multiscale morphology and the biomechanical properties of tendons and ligaments.

Ultrastructural response of tendon to excessive level or duration of tensile load supports that collagen fibrils are mechanically continuous

The basic collagen fibril structure of tendons continues to be debated in the literature. Some studies have proposed that collagen fibrils are longitudinally discontinuous, with the load-bearing ability of tendon dependent on interfibrillar shear strength. Other evidence indicates that collagen fibrils are probably structurally continuous, running uninterrupted from osteotendinous to myotendinous junction. In this study we explored the question of collagen fibril continuity in tendon by examining fibril response to tendon loading. Tendons were subjected to high stress and/or long duration tensile loading routines, after which we examined the ultrastructure of the tendons using differential scanning calorimetry and scanning electron microscopy, comparing the results from the loaded tendons to control samples taken from the same tendons prior to loading. Our results show that under ramp loading, collagen fibril damage begins near the end of the linear region in the stress-strain response (i.e., near the yield point). When tendons are allowed to gradually elongate under static load, tendon rupture is caused by failure of collagen fibrils, not uncontrolled slippage between fibrils. Our findings indicate that the collagen fibrils of tendon are at least sufficiently long to be mechanically continuous, meaning that tensile failure of tendon does not occur as the result of uncontrolled slippage between fibrils, but by failure of the fibrils themselves.

Bayesian inference of constitutive model parameters from uncertain uniaxial experiments on murine tendons

Constitutive models for biological tissue are typically formulated as a mixture of constituents and the overall response is then assembled by superposition or compatibility. This ensures the stress response of the biological tissue to be in the range of a given constitutive relationship, guaranteeing that at least one parameter combination exists so that an experimental response can be sufficiently well captured. Another, perhaps more challenging, problem is to use constitutive models as a proxy to infer the structure/function of a biological tissue from experiments. In other words, we determine the optimal set of parameters by solving an inverse problem and use these parameters to infer the integrity of the tissue constituents. In previous studies, we focused on the mechanical stress-stretch response of the murine patellar tendon at various age and healing timepoints and solved the inverse problem using three constitutive models, i.e., the Freed-Rajagopal, Gasser-Ogden-Holzapfel and Shearer in order of increasing microstructural detail. Herein, we extend this work by adopting a Bayesian perspective on parameter estimation and implement the constitutive relations in the tulip library for uncertainty analysis, critically analyzing parameter marginals, correlations, identifiability and sensitivity. Our results show the importance of investigating the variability of parameter estimates and that results from optimization may be misleading, particularly for models with many parameters inferred from limited experimental evidence. In our study, we show that different age and healing conditions do not correspond to statistically significant separation among the Gasser-Ogden-Holzapfel and Shearer model parameters, while the phenomenological Freed-Rajagopal model is instead characterized by better indentifiability and parameter learning. Use of the complete experimental observations rather than averaged stress-stretch responses appears to positively constrain inference and results appear to be invariant with respect to the scaling of the experimental uncertainty.

Experimental Evaluation of Vibration Response of External Post-Tensioned Tendons with Corrosion

This study investigates the vibration responses of external post-tensioned (PT) tendons based on experimental data. The vibration signals measured from four large-scale external post-tensioned tendon specimens subjected to localized corrosion until severe level of damage were accumulated. A series of impact tests was conducted to measure lateral vibration signals and the variation in the tension was continuously monitored using a load cell. The acquired vibration signals were evaluated using an axially-tensioned beam model in which the properties were varied to reflect the loss of tension and the reduction in the bending stiffness caused by corrosion damage. A comparison between the experimental data and the analytical results indicates that the natural frequencies were shifted as the residual tension decreased but were influenced by corresponding grout damage in a limited range. As a result, the frequency response was not appreciably affected by the damage level and the tension remained as the primary structural parameter of the external PT tendon with damage.

Insulin‐like Growth Factor‐1 Receptor Signaling Regulates Adult Tendon Growth Through ERK1/2‐dependent Tenocyte Proliferation and Initiation of Protein Synthesis

Tendon fibroblasts, or tenocytes, are the main cell type in tendon and serve to synthesize and maintain collagen fibrils and other extracellular matrix proteins within the tissue. Despite the high prevalence of tendon injury, the underlying biological mechanisms of postnatal tendon growth and repair are not well understood. Insulin‐like growth factor (IGF‐1) signaling is stimulated by growth hormone (GH) and promotes the growth and development of many different tissue types. While IGF‐1 is a potent hypertrophic signaling molecule in skeletal muscle, less is known about the role of IGF‐1 in tendon biology. Therefore, the purpose of this study was to determine the importance of IGF‐1 signaling in postnatal tendon growth. Our hypothesis was that IGF‐1 signaling is required for the response of tendon to a mechanical load stimulus. To test this hypothesis, we used both in vitro studies of cultured tenocytes, and in vivo studies using genetically modified mice that allowed us to delete the IGF‐1 receptor (IGF1R) specifically in tenocytes. Treatment of tenocytes in vitro with IGF‐1 increased the expression of Mki67 transcript levels after 24 hours, and resulted in activation of the Akt and ERK1/2 pathways. When tenocyte proliferative activity was measured, cells treated with IGF‐1 displayed increased proliferation compared to controls, but inhibition of ERK prevented the IGF‐1‐mediated increase in cell proliferation and Mki67 (Ki67) expression. Inhibition of Akt signaling did not impact tenocyte proliferation or Mki67 expression. In addition, treatment of tenocytes with IGF1 increased the rate of protein synthesis and ribosomal RNA expression. Analysis of mechanically overloaded plantaris tendons in vivo revealed significantly reduced size of the neotendon matrix which forms around the original tendon in response to mechanical loads, and total tendon cross‐sectional area (CSA) at 14 days in the IGF‐1 knockdown mice compared to the controls. This was accompanied by decreased number of proliferating cells and proteins involved in cell proliferation and initiation of translation, as measured by proteomic analysis. The results of this work support IGF‐1 signaling as a fundamental component of postnatal tendon growth in response to mechanical loading, specifically through the regulation of ERK1/2‐dependent tenocyte proliferation and initiation of protein synthesis. Further studies of the growth factors and proteins involved, and the potential to evaluate IGF‐1 to promote tendon regeneration, are warranted.Support or Funding InformationNIH R01‐AR063649 and F32‐AR067086.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Adaptation of Tendon Structure and Function in Tendinopathy With Exercise and Its Relationship to Clinical Outcome

Exercise is seen as the most evidence-based treatment for managing tendinopathy and although the type of exercise used to manage tendinopathy may induce adaptation in healthy tendons, it is not clear whether these adaptations occur in tendinopathy and if so whether they are associated with improved clinical outcomes. The aim of the study was to synthesize available evidence for adaptation of the Achilles tendon to eccentric exercise and the relationship between adaptation (change in tendon thickness) and clinical outcomes among people with Achilles tendinopathy. The search was performed in September 2018 in several databases. Studies investigating the response (clinical outcome and imaging on ultrasound/magnetic resonance imaging) of pathological tendons (tendinopathy, tendinosis, and partial rupture) to at least 12 weeks of eccentric exercise were included. Multiple studies that investigated the same interventions and outcome were pooled and presented in effect size estimates, mean difference, and 95% confidence intervals if measurement scales were the same, or standard mean difference and 95% confidence intervals if measurements scales were different. Where data could not be pooled the studies were qualitatively synthesized based on van Tulder etal. Eight studies met the inclusion and exclusion criteria and were included in the review. There was strong evidence that Achilles tendon thickness does not decrease in parallel with improved clinical outcomes. Whether a longer time to follow-up is more important than the intervention (ie,just the time per se) for a change in tendon thickness remains unknown. Future studies should investigate whether exercise (or other treatments) can be tailored to optimize tendon adaptation and function, and whether this relates to clinical outcomes.

An experimental and numerical study on the transverse deformations in tensile test of tendons

The transverse deformations of tendons assessed in tensile tests seems to constitute a controversial issue in literature. On the one hand, large positive variations of the Poisson’s ratio have been reported, indicating volume reduction under tensile states. On the other hand, negative values were also observed, pointing out an auxetic material response. Based on these experimental observations, the following question is raised: Are these large and discrepant transverse deformations intrinsically related to the constitutive response of tendons or they result from artifacts of the mechanical test setup? In order to provide further insights to this question, an experimental and numerical study on the transverse kinematics of tendons was carried out. Tensile experiments were performed in branches of deep digital flexor tendons of domestic porcine, where the transverse displacements were measured by two high-speed, high-accuracy optical digital micrometers placed transversely to one another. Aiming at a better understanding of the effects of the mechanical test setup in the transverse measurements, a three-dimensional finite element model is proposed to resemble the tensile experiment. The main achieved results strongly support the following hypotheses regarding tensile tests of tendons: the clamping region considerably affects the kinematics of the specimen even at a large distance from the clamps; the transverse deformations are mainly ruled by stiff fibers embedded in a soft matrix; the generalization of the Poisson’s ratio to draw conclusions about changes in volume of tendons may lead to misinterpretations.

Loads and Response of a Tension Leg Platform Wind Turbine with Non-Rotating Blades: An Experimental Study

This paper describes model testing of a Tension Leg Platform Wind Turbine (TLPWT) with non-rotating blades to better understand its motion and tendon responses when subjected to combined wind and unidirectional regular wave conditions. The TLPWT structure is closely based on the National Renewable Energy Laboratory (NREL) 5 MW concept. Multiple free decay tests were performed to evaluate the natural periods of the model in the key degrees of freedom, whilst Response Amplitude Operators (RAOs) were derived to show the motion and tendon characteristics. The natural periods in surge and pitch motions evaluated from the decay tests had a relatively close agreement to the theoretical values. Overall, the tested TLPWT model exhibited typical motion responses to that of a generalised TLP with significant surge offsets along with stiff heave and pitch motions. The maximum magnitudes for the RAOs of surge motion and all tendons occurred at the longest wave period of 1.23 s (~13.0 s at full-scale) tested in this study. From the attained results, there was evidence that static wind loading on the turbine structure had some impact on the motions and tendon response, particularly in the heave direction, with an average increase of 13.1% in motion amplitude for the tested wind conditions. The wind had a negligible effect on the surge motion and slightly decreased the tendon tensions in all tendons. The results also showed the set-down magnitudes amounting to approximately 2–5% of the offset. Furthermore, the waves are the dominant factor contributing to the set-down of the TLPWT, with a minimal contribution from the static wind loading. The results of this study could be used for calibrating numerical tools such as CFD codes.

FeetBeat: A Flexible Iontronic Sensing Wearable Detects Pedal Pulses and Muscular Activities.

Human feet have long been considered in close association with whole-body health, from which abundant cardiovascular and skeletomuscular information can be extracted. In this study, we aim to develop the world's first foot-based wearable system that can detect both pedal pulses and muscular activities, referred to as FeetBeat. Utilizing the flexible iontronic sensing technology, we have constructed and characterized a five-unit sensing array for detection of both pedal pulse signals and muscular activities. It is integrated into the tongue of an athletic shoe for real-time signal acquisition. Additionally, the linear array allows alignment-free capture of pulse signals and also provides a spatial reference to muscular activities. An ultrahigh sensitivity of up to 1nF/mmHg has been achieved for individual units, with a range of 1 to 200mmHg. The pedal pulse waveforms have been detected to derive vital health signs, such as heart rates (HR) and respiratory rates, of which the pulse-derived HR is compared with the electrocardiogram. Moreover, individual tendon responses have been acquired to analyze different pedal gestures, from which multi-channel signals can be used to distinguish different activities. The FeetBeat device has shown the potential to be the world's first wearable platform to simultaneously analyze both vital signals and body activities from the measurable pedal pulse waveforms and muscular responses in a natural and unobtrusive fashion. The data-collecting wearable system provides a highly valuable means to assess the personalized health as well as daily activities on a continuous basis.

Advanced glycation end-product cross-linking inhibits biomechanical plasticity and characteristic failure morphology of native tendon.

Advanced glycation end-products (AGEs) are formed in vivo from the nonenzymatic reaction between sugars and proteins. AGEs accumulate in long-lived tissues like tendons, cross-linking neighboring collagen molecules, and are in part complicit in connective tissue pathologies experienced in aging and with diabetes. We have previously described discrete plasticity: a characteristic form of nanoscale collagen fibril damage consisting of serial fibril kinking and collagen denaturation that occurs in some mechanically overloaded tendons. We suspect that this failure mechanism may be an adaptive trait of collagen fibrils and have published evidence that inflammatory cells may be able to recognize and digest the denatured collagen produced by overload. In this study, we treated bovine tail tendons with ribose to simulate long-term AGE cross-linking in vitro. We hypothesized that a high degree of cross-linking would inhibit the intermolecular sliding thought to be necessary for discrete plasticity to occur. Tendons were mechanically overloaded, and properties were investigated by differential scanning calorimetry and scanning election microscopy. Ribose cross-linking treatment altered the mechanical response of tendons after the yield point, significantly decreasing postyield extensibility and strain energy capacity before rupture. Coincident with altered mechanics, ribose cross-linking completely inhibited the discrete plasticity failure mechanism of tendon. Our results suggest that discrete plasticity, which may be an important physiological mechanism, becomes pathologically disabled by the formation of AGE cross-links in aging and diabetes. NEW & NOTEWORTHY We have previously shown that mechanically overloaded collagen fibrils in mammalian tendons accrue nanoscaled damage. This includes development of a characteristic kinking morphology within a shell of denatured collagen: discrete plasticity. Here, using a ribose-incubation model, we show that advanced glycation end-product cross-linking associated with aging and diabetes completely inhibits this mechanism. Since discrete plasticity appears to cue cellular remodeling, this result has important implications for diabetic tendinopathy.

Ultrasound guided tendon therapies: Options and evidence

Tendon injury is very common, particularly in active people. Common examples include pathology of the rotator cuff, common extensor and flexor tendons at the elbow, gluteal tendons at the greater trochanter, patellar tendon and Achilles tendon. Healthy tendon has an ordered structure that includes uniform flat-shaped tenocyte cells, collagen fibers organised and layered end-to-end and side-by-side, and a structurally organized extracellular matrix (ECM). Response of tendon to injury is a complex pathological process for which the term ‘tendinosis’ is used. This process consists of early disruption of collagen fibre orientation, followed by cell proliferation, angiogenesis, change in tenocyte cell shape, and collagen and extracellular matrix breakdown. Tendon cell death and depletion at the centre of the affected region leads to further collagen and extracellular matrix breakdown, followed by fatigue healing and degenerative changes. Treatment options for tendon pathologies include conservative measures such as modification of behavior, strapping, oral anti-inflammatories, and lithotripsy. Ultrasound guided injection techniques include HCLA into, or adjacent to, the tendon, dry needling of the affected tendon, autologous blood injection, platelet rich plasma (PRP) and autologous tenocyte injection (ATI). Surgical options such as debridement, division or reconstruction of the affected tendon may be used when conservative treatments have failed. ATI is a cell-based therapy that involves the harvesting of healthy tendon from the patient. The autologous donor tendon material is obtained using ultrasound guided percutaneous core biopsy, usually of the quadriceps or patellar tendon. Adequate volume of tendon, sterile technique and minimal trauma to the healthy tendon and adjacent tissues is essential. This material is cultured for 6 weeks to produce a suspension of tenocytes, which are injected under ultrasound guidance into the abnormal tendon. The aim of the procedure is to grow new tendon tissue within the abnormal structure, restore function and relieve pain. The presence of multiple available treatments implies that no single treatment is reliably effective. Various treatments may be advocated based on multiple factors such as individual experience and expertise, plus local availability. A review of these treatments will be presented, with an attempt to make sense of the currently available evidence.

Response of the Injured Tendon to Growth Factors in the Presence or Absence of the Paratenon

Background: The paratenon is important for Achilles tendon healing. There is much interest in the use of exogenous growth factors (GFs) as potential agents for accelerating the healing of damaged Achilles tendons. Purpose/Hypothesis: The present study used a rat model to study the responses of the injured Achilles tendon to GFs in the presence or absence of the paratenon. The hypothesis was that responses of the injured tendon to GFs would be lower in the absence of a paratenon. Study Design: Controlled laboratory study. Methods: A 4-mm defect was created in the right Achilles tendon of 60 skeletally mature rats, which were treated with a validated combination of GFs (bFGF, BMP-12, and TGF-β1). Animals were randomly assigned to the intact paratenon (IP) group or resected paratenon (RP) group. Healing was studied anatomically, mechanically, and histologically after 1, 2, and 4 weeks. Results: IP tendons showed improved healing compared with RP tendons. IP tendons were significantly stronger (32.2 N and 48.9 N, respectively) than RP tendons (20.1 N and 31.1 N, respectively) after 1 and 2 weeks. IP tendons did not elongate as much as RP tendons and had greater cross-sectional areas (18.0 mm2, 14.4 mm2, and 16.4 mm2, respectively) after 1, 2, and 4 weeks compared with RP tendons (10.5 mm2, 8.4 mm2, and 11.9 mm2, respectively). On histology, earlier collagen deposition and parallel orientation of fibrils were found for IP tendons. Conclusion: The paratenon is essential for efficient Achilles tendon healing. Healing with GFs in this Achilles tendon defect model was superior in the presence of the paratenon. Clinical Relevance: Biological approaches to tendon engineering using GFs are in vogue and have been shown to improve healing of the rat Achilles tendon, most likely by inducing progenitor cells located within the paratenon. Clinically, resection or incision of the paratenon has been proposed for wound closure. Our data demonstrate the fundamental importance of the paratenon, which therefore should be preserved during Achilles tendon repair, especially if augmented with products such as platelet-rich plasma or autologous conditioned serum that are rich in GFs.

Computational model for the patella onset.

The patella is a sesamoid bone embedded within the quadriceps tendon and the patellar tendon that articulates with the femur. However, how is it formed is still unknown. Therefore, here we have evaluated, computationally, how three theories explain, independently, the patella onset. The first theory was proposed recently, in 2015. This theory suggested that the patella is initially formed as a bone eminence, attached to the anterodistal surface of the femur, while the quadriceps tendon is forming. Thereafter, a joint develops between the eminence and the femur, regulated by mechanical load. We evaluated this theory by simulating the biochemical environment that surrounds the tendon development. As a result, we obtained a patella-like structure embedded within the tendon, especially for larger flexion angles. The second and third theories are the most accepted until now. They state that the patella develops within tendons in response to the mechanical environment provided by the attaching muscles. The second theory analyzed the mechanical conditions (high hydrostatic stress) that (according to previous Carter theories) lead to the differentiation from tendon to fibrocartilage, and then, to bone. The last theory was evaluated using the self-optimizing capability of biological tissue. It was considered that the development of the patella, due to tissue topological optimization of the developing quadriceps tendon, is a feasible explanation of the patella appearance. For both theories, a patella onset was obtained as a structure embedded within the tendon. This model provided information about the relationship between the flexion angle and the patella size and shape. In conclusion, the computational models used to evaluate and analyze the selected theories allow determining that the patella onset may be the result of a combination of biochemical and mechanical factors that surround the patellar tendon development.

Effect of intraoperative positioning on postoperative neurological status in cats after perineal urethrostomy.

The aim of this study was to evaluate and quantify the changes in neurological status in cats after perineal urethrostomy performed in dorsal and ventral recumbency. This was a prospective, randomised study. Twenty male castrated cats with feline lower urinary tract disease presented for perineal urethrostomy were enrolled in this study. Surgery was performed in either dorsal recumbency (group A) or ventral recumbency (group B). Motor response of patellar tendon, gastrocnemius muscle, pelvic limb withdrawal and perineal reflexes, as well as the presence of spinal pain in the lumbosacral region, motor function of the tail and faecal continence, were examined before surgery, and 24 h and 14 days after surgery. The animals had a mean weight of 5.07 ± 1.08 kg, with a mean age of 6.12 ± 1.85 years. Weight and age were not significantly different between groups A and B (both P = 0.897). All tested parameters of the neurological examination performed prior to surgery were considered normal in both groups (P = 1). The comparison between neurological examinations (perineal reflex and spinal pain) before and 24 h after surgery revealed a significantly decreased briskness of the perineal reflex and an increased occurrence of spinal pain 24 h after surgery (P = 0.043 and P = 0.031, respectively). However, the changes of aforementioned parameters were statistically insignificant (P = 0.249 and P = 0.141) between groups A and B. The other parameters (patellar tendon, pelvic limb withdrawal and gastrocnemius muscle reflexes, motor function of the tail and faecal continence) were statistically insignificant (P = 1) before surgery and 24 h after surgery, as well as between groups A and B 24 h after surgery. Results of all tested parameters were statistically insignificant (P = 1) before surgery and 14 days after surgery, as well as between groups A and B 14 days after surgery. The briskness of the perineal reflex was significantly decreased and the occurrence of spinal pain significantly increased 24 h after surgery. A parallel with a low-grade positioning-dependent nerve injury as described in human medicine may be drawn. However, no positioning method was proven to be superior to the other.

Sex Differences in Mechanical Properties of the Achilles Tendon: Longitudinal Response to Repetitive Loading Exercise.

Lepley, AS, Joseph, MF, Daigle, NR, Digiacomo, JE, Galer, J, Rock, E, Rosier, SB, and Sureja, PB. Sex differences in mechanical properties of the Achilles tendon: Longitudinal response to repetitive loading exercise. J Strength Cond Res 32(11): 3070-3079, 2018-Sex differences have been observed in the mechanical properties of the Achilles tendon, which may help to explain the increased risk of injury in men. However, the response and recovery of tendon mechanics to repetitive loading exercise, as well as sex-dependent responses, are not well understood. The purpose of our study was to compare Achilles tendon mechanical properties between men and women before, immediately after, and 60 minutes after a repetitive loading exercise. Seventeen female (age: 24.0 ± 3.9 years; height: 167.4 ± 6.9 cm; and mass: 64.9 ± 8.5 kg) and 18 male (age: 23.9 ± 2.4 years; height: 179.2 ± 5.09 cm; and mass: 78.4 ± 8.7 kg) recreationally active individuals volunteered. Using isokinetic dynamometry and diagnostic ultrasound, baseline levels of Achilles tendon force, elongation, stiffness, stress, strain, and Young's modulus were assessed before 100 successive calf-raise exercises using a Smith machine at 20% of participant body mass. Outcomes were reassessed immediately and 60 minutes after exercise. Women exhibited less Achilles tendon force, stiffness, stress, and modulus compared with men, regardless of time point. Both sexes responded to repetitive loading exercise similarly, with immediate decreases in mechanical properties of the Achilles tendon from baseline to immediately after exercise. Tendon properties were observed to be equal to baseline values at 60-minute postexercise. Baseline differences in tendon properties may help to explain the disparity in injury risk because both sexes responded to and recovered from exercise similarly. Future research should aim to include additional time points (both leading up to and after 60 minutes), and assess tendon responses to more sport-specific activities, while also including patients diagnosed with Achilles tendon injuries.