Tendon Damage Research Articles

Enhancing structural damage evaluation of PC girder bridges through digital twinning Bayesian model updating

Developing a unified analytical framework to assess the structural performance of deteriorated prestressed concrete (PC) girder bridges is important for their maintenance. This study aims to construct a physics-based digital twin framework for PC girder bridges incorporating Bayesian model selection and updating, a high-fidelity three-dimensional (3D) finite element (FE) model, and a method for simulating prestressed tendon damage. In this study, three PC girder specimens were designed and tested to evaluate the effects of tendon rupture near the anchorage region on structural performance. Bayesian model selection was used to determine the most plausible model class based on the estimated model evidence. The most probable values (MPVs) of the model parameters, derived from the estimated posterior probability density functions (PDFs), were then used to calibrate the FE model, which reflects a healthy state of the PC girder bridge. This updated FE model serves as the baseline for conducting what-if scenario simulations. Subsequently, nonlinear segments of the constitutive model, obtained from coupon tests, and a simulation method for tendon rupture were incorporated into the updated FE model. Nonlinear static simulation results obtained through the updated model were found to be consistent with both the observed crack pattern and the load–deflection curve. The reliability of the digital twinning FE model for assessing tendon damage and for predicting the residual load-bearing capacity was verified through comparison with measured data. Therefore, the digital twinning Bayesian model updating approach shows potential applications in continuous structural health monitoring (SHM) of PC bridges.

Tendon involvement and its association with pain and hand function in patients with osteoarthritis of the hand.

To characterise the frequency and influence of tenosynovitis and tendon damage on pain and hand function using clinical examination and ultrasound (US) in hand osteoarthritis (HOA). We included 86 patients with HOA and 23 age- and sex-matched control subjects. Extensor and flexor tendons of both hands were assessed by clinical examination and US for tenosynovitis, tendon damage. Conventional radiographs were acquired. Hand function was evaluated by the function subtest of the M-SACRAH questionnaire and the Moberg pick-up test. K-means cluster analyses was calculated to assess clusters based on radiographic features and sonographic tendon scores. Ultrasound identified the involvement of ≥ 1 tendon in 60/86 (69.8%) HOA patients compared with 2/23 (8.7%) subjects (p< 0.01) in the control group. In the HOA group, US detected tendon damage more often in flexor tendons compared with extensor tendons (2.1% 0.9%, p= 0.03), while tenosynovitis was observed more often in extensor tendons compared with flexor tendons (8% vs 0.6%, p< 0001). The sensitivity and specificity of clinical examination to detect tendon involvement was 81.4% and 34.6%, respectively on the patient level and 14.5% and 83.8% on the tendon level. The cluster analyses revealed one cluster with more radiographic features of HOA and more tendon damage while more tenosynovitis was found in cluster 2. M-SACRAH function did not correlate with tendon involvement on US. This study revealed a high frequency of tendon involvement in HOA. Tendon involvement on US did not impact hand function or self-reported pain.

Myotendinous Junction Anesthesia: An Alternative Infiltration Site for Ultrasound-Guided Injections

The myotendinous junction is a highly specialized and complex structure between muscle and tendon. In recent years, various procedures have directly targeted the tendon, with corticosteroid, platelet-rich plasma, or biological therapy infiltrations being prominent. However, these interventions are painful, corticosteroids have demonstrated tendon damage, and anesthesia negatively impacts tenocyte proliferation and viability when used with platelet-rich plasma in the same injection site. There is a need to adapt the injection site to improve therapy effectiveness and pain tolerance. This article presents a proposal for an ultrasound-guided anesthetic block procedure in the myotendinous junction.

Anchorage Research for CFRP Tendons: A Review.

Carbon fiber reinforced polymer (CFRP) tendons are composite materials that offer significant advantages in terms of tensile strength and lightweight properties. They are being increasingly utilized in the construction industry, particularly in bridge cables and building structures. However, due to their relatively poor transverse mechanical properties compared to steel cables, securing these tendons with anchors presents a challenge. This paper reviews the structure and force characteristics of three types of anchors for CFRP tendons-clamping anchorage, bonded anchorage, and composite anchorage-analyzes and summarizes the anchorage characteristics and damage mechanisms of each type of anchorage, and highlights that the optimization of the mechanical properties of the tendons is key to the design and research of anchoring systems. The new composite anchorage offers comprehensive advantages, such as minimal tendon damage at the anchorage section, more uniform stress distribution, and better anchorage performance, despite being more complex in design compared to single-type anchorages. However, there remain challenges and research gaps in testing and validating these anchoring systems under realistic loading and environmental conditions, including impacts, cyclic stresses, humidity, and high temperatures. Future efforts should focus on developing new testing techniques and models to simulate real-world conditions, enabling more accurate assessments of anchorage performance and longevity. By doing so, we can fully harness the mechanical properties of CFRP tendons and further enhance the safety and efficiency of our built environment.

Damage Detection in External Tendons of Post-Tensioned Bridges

This study investigates damage detection in the tendons of post-tensioned segmental box girder bridges, focusing on the vibration-based technique and its application in conjunction with the Precursor Transformation Matrix (PTM). Due to the critical role of bridge tendons in structural integrity, efficient and timely detection methods are essential. The methodology combines theoretical modeling with Finite Element Method (FEM) simulations and empirical data collection to evaluate the PTM’s effectiveness in identifying tendon damage. Key results indicate that the PTM, when paired with vibration analysis, enhances the identification and localization of damage, proving to be a robust method in structural health monitoring. This approach not only speeds up damage detection but also potentially lowers maintenance costs by pinpointing specific damage sites, thereby preventing widespread structural failures. The findings offer a promising tool for ensuring the longevity and safety of post-tensioned bridges.

Acoustic emission technology-based waveguide localization method for damaged internal tendons of in-service post-tensioned hollow slab bridges

Prestressing tendons are crucial load-bearing elements in post-tensioned hollow slab bridges. Damage to these tendons significantly reduces the safety, functionality, and longevity of the bridge. Regular monitoring of prestressing tendons is essential for bridge operation. Acoustic emission technology, known for its high accuracy and sensitivity to minor vibrations, is a key technique for monitoring bridge cables. This study proposes a novel dual-sensor acoustic emission localization method for detecting tendon damage in post-tensioned hollow slab bridges, utilizing waveguide technology. The effectiveness of this method is confirmed through hammering tests that simulate acoustic emission damage on operational hollow slab bridges. The proposed method, requiring only two sensors, offers a cost-effective alternative for monitoring the entire span of post-tensioned hollow slab bridges, so that effectively reduces the cost of bridge health monitoring and is easy to be promoted in actual engineering projects.

Dual Dynamic Crosslinked Hydrogel Patch Embodied with Anti‐Bacterial and Macrophage Regulatory Properties for Synergistic Prevention of Peritendinous Adhesion

AbstractThe occurrence of peritendinous adhesion, which hampers the quality and function of the healed tendon, is strongly linked to oxidative stress, inflammatory, and infection that occur after surgery. Tendon damage and repair provide a considerable obstacle for regenerative medicine owing to the absence of patches that possess comprehensive functionality, including self‐healing capacity, anti‐inflammatory and anti‐bacterial properties, as well as tissue repair guidance. A dual dynamic crosslinked network is created by coordination bonds between catechol groups in protocatechuic aldehyde (PA) and Fe3+, as well as a dynamic Schiff base reaction between amino groups in hyaluronic acid‐adipic acid dihydrazide (HA‐ADH) and aldehyde groups in PA. The HA‐ADH@PA/Fe hydrogel exhibits self‐healing ability, tissue adhesion, anti‐bacterial activity, regulation of macrophage polarization via the NF‐κB signaling, oxidative stress elimination, and anti‐inflammation. In addition, a dual‐layer Janus patch is created, taking inspiration from the anatomy and disease progression of tendon adhesion. The inner layer of the patch, which is in direct contact with the operated tendon, is a multifunctional HA‐ADH@PA/Fe hydrogel, encircled further by a poly(ɛ‐caprolactone) (PCL) electrospinning membrane outer layer facing the surrounding tissue. The PCL@HA‐ADH@PA/Fe hydrogel patch reduced tendon adhesion and supported tissue regeneration by stimulating macrophages polarization into an anti‐inflammatory phenotype and resolving both local and systemic inflammation. This research showcased the PCL@HA‐ADH@PA/Fe hydrogel patch as an alternative therapeutic method for preventing the development of adhesions around tendons.

Diagnostic value of Achilles tendon shear wave elastography in patients with ankylosing spondylitis: A case-control study.

Ankylosing spondylitis (AS) can cause peripheral arthritis, tendinitis, enthesitis, and axial skeletal involvement. This study aims to determine early tendon damage by shear wave elastography (SWE) for the Achilles tendon in AS patients. 48 AS patients and 48 asymptomatic individuals were included in the study. Participants were systematically examined with B-mode, power Doppler, and SWE using a high-resolution linear 6-15 MHz probe. Bilateral Achilles tendon stiffness, thickness, and vascularity were evaluated. Measurements were taken from the middle third of the Achilles tendon in the sagittal plane. Difference between the two groups was evaluated with statistical methods. Receiver operating characteristic analysis was performed to test the diagnostic performance of Achilles tendon stiffness. Additionally, the Spearman correlation test examined the relationship between Achilles tendon stiffness and disease duration. The difference between the two groups regarding Achilles tendon stiffness was statistically significant (p < 0.05). It was observed that Achilles tendon stiffness decreased in the patient group compared with the control group. The diagnostic value of Achilles tendon stiffness measured by SWE was found to be high. A negative correlation was detected between disease duration and tendon stiffness (p < 0.05). In patients diagnosed with AS, deterioration in the Achilles tendon structure was observed, and a significant decrease in tendon stiffness compared with the healthy population. It has been determined that these changes in the Achilles tendon are related to the duration of the disease.

Mohawk protects against tendon damage via suppressing Wnt/β-catenin pathway

Degenerative tendon injuries are common clinical problems associated with overuse or aging, and understanding the mechanisms of tendon injury and regeneration can contribute to the study of tendon healing and repair. As a transcription factor, Mohawk (Mkx) is responsible for tendons development, yet, the roles of which in tendon damage remain mostly elusive. In this study, using Mkx overexpressed mice on long treadmill as an in vivo model and MkxOE Achilles tenocytes stimulated by equiaxial stretch as an in vitro model, we anaylsed the effects of Mkx overexpression on the tendon. Mkx and tendon tension strength were decreased after the expose to excessive mechanical forces, and Mkx overexpression protected the tendon from damage. Moreover, we revealed that the Wnt/β-catenin activation, inflammation, and Runx2 expression were increased at the injured Achilles tendon, upregulated Mkx significantly reversed the increased Wnt/β-catenin pathway, Tnf-α, Il-1β, and Il-6 levels, and reduced tendon cell damage. However, Wnt3a, IWR and BIO had not significantly affected the Mkx expression in achilles tenocytes. In conclusion, Mkx is involved in tendon healing and protects the tendon from damage through suppressing Wnt/β-catenin pathway, suggesting Mkx/Wnt/β-catenin pathway may be potential therapeutic targets for tendon damage.

MOVEMENT DATA ANALYSIS AS A NOVEL PREDICTIVE TECHNOLOGY FOR TENDON REPAIR

Digital Ventilated Cages (DVC) offer an innovative technology to obtain accurate movement data from a single mouse over time [1]. Thus, they could be used to determine the occurrence of a tendon damage event as well as inform on tissue regeneration [2,3]. Therefore, using the mouse model of tendon experimental damage, in this study it has been tested whether the recovery of tissue microarchitecture and of extracellular matrix (ECM) correlates with the motion data collected through this technology.Mice models were used to induce acute injury in Achilles tendons (ATs), while healthy ones were used as control. During the healing process, the mice were housed in DVC cages (Tecniplast) to monitor animal welfare and to study biomechanics assessing movement activity, an indicator of the recovery of tendon tissue functionality. After 28 days, the AT were harvested and assessed for their histological and immunohistochemical properties to obtain a total histological score (TSH) that was then correlated to the movement data.DVC cages showed the capacity to distinguish activity patterns in groups from the two different conditions. The data collected showed that the mice with access to the mouse wheel had a higher activity as compared to the blocked wheel group, which suggests that the extra movement during tendon healing improved motion ability. The histological results showed a clear difference between different analyzed groups. The bilateral free wheel group showed the best histological recovery, offering the highest TSH score, thus confirming the results of the DVC cages and the correlation between movement activity and structural recovery.Data obtained showed a correlation between TSH and the DVC cages, displaying structural and movement differences between the tested groups. This successful correlation allows the usage of DVC type cages as a non-invasive method to predict tissue regeneration and recovery.Acknowledgements: This research is part of the P4FIT project ESR13, funded by the H2020-ITN-EJD MSCA grant agreement No.955685.

Histopathological Study of the Effect of Xenogeneic Platelet-Rich Fibrin on Achilles Tendon Healing in Rabbit

Tendon is a mechanical bridge that transforms the force generated by muscle contraction into movement. This tissue is well known for its low cellularity and vascularity; therefore, any tendon damage is characterized by a slow and inefficient healing process resulting in mechanically, structurally, and functionally inferior tissue. The current study aimed to evaluate the effect of the regenerative capacity of xenogeneic platelet-rich fibrin on the acceleration of Achilles tendon healing in rabbits. 24 adult rabbits weighing (1.5-2) kg were used in this study. The animals were divided equally into three groups: A-PRF group, in which the tendon defect was treated with xenogeneic Advance-platelet rich fibrin; L-PRF group, which used xenogeneic for tendon defect treatment; and control groups treated with normal saline. Clinical investigation of the rabbits during the experiment period revealed improvement of lameness and disappearance of swelling and redness at the operation site in the A-PRF and L-PRF groups compared to the control group at the same period. Histopathological examination revealed a good tendon healing process in the A-PRF group characterized by a highly organized Achilles tendon and lightly stained collagen fibers arranged in parallel. At the same time, these are less evident in the L-PRF group. In conclusion, this study suggests that xenogeneic Advanced platelet-rich fibrin treatment can be useful as a biomaterial for accelerating Achilles tendon healing in rabbits and this biomaterial. Keywords: Xenogeneic platelet-rich fibrin; Rabbit Achilles tendon; tendon healing; Advanced platelet-rich fibrin; Iraq.

Skin microbiota metabolism of natural products from comfrey root (Symphytum officinale L.)

Ethnopharmacological relevanceComfrey root (Symphytum officinale L., Boraginaceae) has been used in folk medicine for a long time to treat different diseases. It is recommended for swellings, phlebitis, contusions, gastro-duodenal ulcers, respiratory diseases, and metrorrhagia. Currently, preparations from S. officinale are only topically used due to its wound-healing effects, and for reducing inflammation and the treatment of broken bones, tendon damage, painful joints and muscles. Although it is a widespread plant material, little is known about the interaction of externally applied preparations of comfrey with the human skin microbiome. Aim of the studyThe study aims to determine the interaction between human skin microbiota and the comfrey root extracts, by monitoring the biotransformation of the constituents present in the extract and evaluating changes in the population of the skin microbiota in an ex vivo setting. Material and methodsThe comfrey root extract was incubated with the human skin microbiota from ten healthy donors. The UHPLC-DAD-MSn analysis determined the composition of the raw extract and the microbial metabolites. Bacterial genomic DNA was extracted and examined by amplification sequencing of the 16S rDNA to determine changes in the bacterial composition. ResultsThe hydroethanolic extract of comfrey root primarily consists of phenolic acids, pyrrolizidine alkaloids, and their derivatives, and lignans. The natural products present in the extract underwent biodegradation by the skin microbiota, leading to the formation of smaller molecules. It was observed that the skin microbial metabolism primarily focused on modifying the derivatives of pyrrolizidine alkaloids. It resulted in the production of deacetylated and deesterificated compounds. However, it did not lead to the conversion of these compounds into free alkaloids. ConclusionsThe microbiota-triggered biotransformation of the comfrey root extract was observed. A few N-oxides were metabolized to deacetylated and deesterificated forms in ex vivo conditions. It suggests that the intermittent external applications of comfrey preparations perchance are unlikely to pose a substantial risk. While it even may serve as a potential factor influencing the extract activity in treating skin diseases.

A three-dimensional analysis of the tibialis anterior tendon: emphasizing tendon insertion patterns for effective repair and understanding hallux valgus development.

The present study aimed to evaluate the insertion site of the tibialis anterior tendon three-dimensionally. Seventy lower limbs were dissected. The tibialis anterior tendon was dissected to verify the insertion site to the medial cuneiform and the base of the first metatarsal bone. The three-dimensional (3D) territory of the tibialis anterior tendon insertion on the medial cuneiform and the first metatarsal bones was measured on a reconstructed 3D model. The insertion pattern of the tibialis anterior tendon was classified into three types, the most common being Type I: a single tibialis anterior tendon dividing into two equal-sized bands to the medial cuneiform and base of the first metatarsal bone (57.1%, 40/70 of cases). The 3D territory of the tibialis anterior tendon was larger in the plantar aspect than in the medial side of both the medial cuneiform and the base of the first metatarsal bone. The width of the tendon inserted into the medial cuneiform was wider than that inserted into the first metatarsal bone. The tibialis anterior tendon was more commonly attached to the plantar part than the medial part in both the medial cuneiform and the base of the first metatarsal bone. This anatomical information will help surgeons perform anatomical reconstruction of the tibialis anterior tendon, reduce further tendon damage in the first metatarsocuneiform joint area and also provide valuable knowledge to improve understanding of hallux valgus pathogenesis.

Poster 390: Systematic Review of SARMs Abuse in Athletes

Objectives: Selective Androgen Receptor Modulators (SARMs) are small-molecule compounds that exert agonist and antagonist effects on androgen receptors in a tissue-specific fashion. SARMs are not FDA approved in the USA, but are readily available for purchase online. Increasingly, athletes have turned to SARMs in recent years as a means of augmenting lean muscle mass, evidenced by positive tests across multiple athletic organizations including the NFL, NBA, UFC, NCAA, and Olympics. The safety of SARMs for anabolic effects has not been established, and case reports associate SARMs with deleterious effects, including drug-induced liver injury (DILI), myocarditis, and tendon rupture. The purpose of this novel systematic review is to provide a comprehensive synthesis of the SARMs literature, in order to help sports medicine clinicians understand the clinical effects, treatment protocols, banned substance implications, and potential contamination of athlete-consumed SARMs. Methods: A systematic review of the English-language literature from PubMed, Cochrane, and Embase was performed according to PRISMA guidelines. Articles relevant to SARMs clinical outcomes, case reports, safety profiles, and doping control were included. Reviews, meta-analyses, editorials, and conference abstracts were excluded. Ostarine (Enobosarm, GTx-027, MK-2886, S-22), Ligandrol (LGD- 4033, VK5211), RAD-140 (Testolone), and Andarine (S-4, GTx-007) were the primary focus, given the reported widespread recreational abuse of these specific SARMs. Results: The literature search yielded 1382 abstracts, and a total of 23 articles from 2011 to 2022 were identified for inclusion. Three of the five clinical trials reported significant increases in lean body mass (LBM) (Table 1). Five studies reported on drug testing screening methods designed for human-use (Table 2). A liquid chromatography with tandem mass spectrometry urine screening method demonstrated the lowest limit of detection for detecting all four SARMs. Five studies analyzed purchased SARMs for contamination (Table 3). Forty-nine samples of Ostarine, Ligandrol, RAD-140, and Andarine were assessed: 26 out of 49 samples (55%) varied substantially from the label by dosing, purity, or type of compound. Eight case reports described 10 cases of recreational SARMs use and treatment, with all articles published in the last 2 years (Table 4). All included patients were male, half were athletes, and all ingested SARMs orally for an average course of 6 weeks. The specific SARM compounds consumed were Ostarine (4/10), Ligandrol (4/10), and RAD-140 (2/10). Several patients presented with jaundice (5/10), pruritus (4/10), and icteric sclera (4/10). 8 of these patients were diagnosed with DILI, 1 was diagnosed with acute myocarditis, and 1 sustained bilateral Achilles tendon ruptures following two courses of SARMs. Conclusions: Athletes most commonly purchase SARMs online, and a majority of these compounds are contaminated with other substances. Ostarine, Ligandrol, and RAD-140 appear to be the most frequently abused SARM compounds. SARM screening modalities include urine, hair, and nail detection. Although SARMs may increase LBM at low doses, case reports suggest SARMs users consume SARMs at much higher doses than studied, which may increase the risk of harmful side effects such as liver injury, cardiovascular events, and tendon damage (perhaps akin to anabolic androgenic steroids). Further basic science and clinical studies are warranted to validate these early reported findings regarding SARMs. [Table: see text][Table: see text][Table: see text][Table: see text]

Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice.

Skeletal shape depends on the transmission of contractile muscle forces from tendon to bone across the enthesis. Loss of muscle loading impairs enthesis development, yet little is known if and how the postnatal enthesis adapts to increased loading. Here, we studied adaptations in enthesis structure and function in response to increased loading, using optogenetically induced muscle contraction in young (i.e., growth) and adult (i.e., mature) mice. Daily bouts of unilateral optogenetic loading in young mice led to radial calcaneal expansion and warping. This also led to a weaker enthesis with increased collagen damage in young tendon and enthisis, with little change in adult mice. We then used RNA sequencing to identify the pathways associated with increased mechanical loading during growth. In tendon, we found enrichment of glycolysis, focal adhesion, and cell-matrix interactions. In bone, we found enrichment of inflammation and cell cycle. Together, we demonstrate the utility of optogenetic-induced muscle contraction to elicit in vivo adaptation of the enthesis.

Overload in a Rat In Vivo Model of Synergist Ablation Induces Tendon Multiscale Structural and Functional Degeneration.

Tendon degeneration is typically described as an overuse injury with little distinction made between magnitude of load (overload) and number of cycles (overuse). Further, in vivo, animal models of tendon degeneration are mostly overuse models, where tendon damage is caused by a high number of load cycles. As a result, there is a lack of knowledge of how isolated overload leads to degeneration in tendons. A surgical model of synergist ablation (SynAb) overloads the target tendon, plantaris, by ablating its synergist tendon, Achilles. The objective of this study was to evaluate the structural and functional changes that occur following overload of plantaris tendon in a rat SynAb model. Tendon cross-sectional area (CSA) and shape changes were evaluated by longitudinal MR imaging up to 8 weeks postsurgery. Tissue-scale structural changes were evaluated by semiquantified histology and second harmonic generation microscopy. Fibril level changes were evaluated with serial block face scanning electron microscopy (SBF-SEM). Functional changes were evaluated using tension tests at the tissue and microscale using a custom testing system allowing both video and microscopy imaging. At 8 weeks, overloaded plantaris tendons exhibited degenerative changes including increases in CSA, cell density, collagen damage area fraction (DAF), and fibril diameter, and decreases in collagen alignment, modulus, and yield stress. To interpret the differences between overload and overuse in tendon, we introduce a new framework for tendon remodeling and degeneration that differentiates between the inputs of overload and overuse. In summary, isolated overload induces multiscale degenerative structural and functional changes in plantaris tendon.

The Healing Effect of Biodegradable Scaffolds Treated with Bone-Marrow Obtained Mesenchymal Stem Cells on Major Tendon Damage in the Dog as a Model.

The present study aimed to evaluate the implantation of decellularized small intestinal submucosa- extracellular matrix )SIS-ECM( seeded with bone marrow mesenchymal stem cells (BM-MSCs) to repair full-thickness Achilles tendon defect. For this purpose, 20 healthy adult stray dogs aged 8-12 months old (15±3 kg of weight) were enrolled in this study under an aseptic environment and general anesthesia. A 1.5 cm-long segment-based resection was performed in the mid-substance of the Achilles tendon in the control group (n=10) that did not receive treatment. While, in the experimental group (n=10), regarding the defect of the tendon, the stumps were bridged with decellularized SIS seeded with BM-MSCs (5×106) cells implanted. Afterward, the stumps of the tendon were sutured using the modified Kessler technique (4-0) polypropylene thread. The biomechanical observations of the tendon defect showed an increase in the tensile strength in the experimental group, compared to the control animals. It should be mentioned that this difference was significant (P≤0.05). Histopathological observations of biopsies harvested after the 4th, 8th, and 12th weeks revealed that the implanted graft had seeded with MSCs enhanced high-quality cellular infiltration and the host tissue healing was improved. Similar to the normal tendon, a dense organized collagenous tissue with high cellularity and vascularity was observed due to the presence of the remodeled ECM. However, the arrangement of collagen-fiber-derived connective tissue appeared to be more dominant than that in the experimental group, with less adhesion in the 12th week post-treatment. These findings suggest that the BM-MSCs inoculated with SIS can be employed to repair a damaged Achilles tendon due to the fact that this combination enhances the regeneration of the affected tendon.

Fatigue-driven compliance increase and collagen unravelling in mechanically tested anterior cruciate ligament

Approximately 300,000 anterior cruciate ligament (ACL) tears occur annually in the United States, half of which lead to the onset of knee osteoarthritis within 10 years of injury. Repetitive loading is known to result in fatigue damage of both ligament and tendon in the form of collagen unravelling, which can lead to structural failure. However, the relationship between tissue’s structural, compositional, and mechanical changes are poorly understood. Herein we show that repetitive submaximal loading of cadaver knees causes an increase in co-localised induction of collagen unravelling and tissue compliance, especially in regions of greater mineralisation at the ACL femoral enthesis. Upon 100 cycles of 4× bodyweight knee loading, the ACL exhibited greater unravelled collagen in highly mineralized regions across varying levels of stiffness domains as compared to unloaded controls. A decrease in the total area of the most rigid domain, and an increase in the total area of the most compliant domain was also found. The results highlight fatigue-driven changes in both protein structure and mechanics in the more mineralized regions of the ACL enthesis, a known site of clinical ACL failure. The results provide a starting point for designing studies to limit ligament overuse injury.

Mammal comparative tendon biology: advances in regulatory mechanisms through a computational modeling.

There is high clinical demand for the resolution of tendinopathies, which affect mainly adult individuals and animals. Tendon damage resolution during the adult lifetime is not as effective as in earlier stages where complete restoration of tendon structure and property occurs. However, the molecular mechanisms underlying tendon regeneration remain unknown, limiting the development of targeted therapies. The research aim was to draw a comparative map of molecules that control tenogenesis and to exploit systems biology to model their signaling cascades and physiological paths. Using current literature data on molecular interactions in early tendon development, species-specific data collections were created. Then, computational analysis was used to construct Tendon NETworks in which information flow and molecular links were traced, prioritized, and enriched. Species-specific Tendon NETworks generated a data-driven computational framework based on three operative levels and a stage-dependent set of molecules and interactions (embryo-fetal or prepubertal) responsible, respectively, for signaling differentiation and morphogenesis, shaping tendon transcriptional program and downstream modeling of its fibrillogenesis toward a mature tissue. The computational network enrichment unveiled a more complex hierarchical organization of molecule interactions assigning a central role to neuro and endocrine axes which are novel and only partially explored systems for tenogenesis. Overall, this study emphasizes the value of system biology in linking the currently available disjointed molecular data, by establishing the direction and priority of signaling flows. Simultaneously, computational enrichment was critical in revealing new nodes and pathways to watch out for in promoting biomedical advances in tendon healing and developing targeted therapeutic strategies to improve current clinical interventions.

Exposure to oxLDL impairs TGF-β activity in human tendon cells

BackgroundPrevious studies have shown that patients with hypercholesterolemia experience elevated levels of oxidized LDL (oxLDL), a molecule which triggers inflammation and collagenase activity. In this study we discovered novel mechanistic effects of oxLDL on tendon cells and the mediators regulating matrix remodeling by analyzing the expression and activity of related proteins and enzymes. These effects may contribute to tendon damage in patients with high cholesterol.MethodsIsolated human tendon cells (male and female donors age 28 ± 1.4 age 37 ± 5.7, respectively) were incubated in the presence or absence of oxLDL. The influence of oxLDL on the expression level of key mRNA and proteins was examined using real time quantitative PCR, ELISA and Western blots. The activities of enzymes relevant to collagen synthesis and breakdown (lysyl oxidase and matrix metalloproteinases) were quantified using fluorometry. Finally, the isolated human tendon cells in a 3D construct were exposed to combinations of oxLDL and TGF-β to examine their interacting effects on collagen matrix remodeling.ResultsThe one-way ANOVA of gene expression indicates that key mRNAs including TGFB, COL1A1, DCN, and LOX were significantly reduced in human tendon cells by oxLDL while MMPs were increased. The oxLDL reduced the activity of LOX at 50 µg/ml, whereas conversely MMP activities were induced at 25 µg/ml (P ≤ 0.01). COL1A1 synthesis and TGF-β secretion were also inhibited (P ≤ 0.05). Adding recombinant TGF-β reversed the effects of oxLDL on the expression of collagens and LOX. OxLDL also impaired collagen matrix remodeling (P ≤ 0.01), and adding TGF-β restored the native phenotype.ConclusionExposure to oxLDL in patients with hypercholesterolemia may adversely affect the mechanical and structural properties of tendon tissue through a direct action of oxLDL on tendon cells, including impairment of TGF-β expression. This impairment leads to disturbed matrix remodeling and synthesis, thereby potentially leading to increased risk of acute or chronic tendon injury. Our discovery may provide an opportunity for developing effective treatments for tendon injury in hypercholesterolemia patients by targeting the TGF-β pathway.