The effect of altered loading following rotator cuff tears in a rat model on the regional mechanical properties of the long head of the biceps tendon

Biceps tendon pathology is a common clinical problem often seen in conjunction with rotator cuff tears. A previous study found detrimental changes to biceps tendons in the presence of rotator cuff tears in a rat model. Therefore, the objective of this study was to utilize this model along with models of altered loading to investigate the effect of altered loading on the initiation of these detrimental changes. We created supraspinatus and infraspinatus rotator cuff tears in the rat and followed these tears with either increased or decreased loading. Mechanical properties were determined along the length of the biceps tendon 4 and 8 weeks following injury. At the insertion site, stiffness increased with decreased loading, while detrimental changes were seen with increased loading 4 weeks following detachments. Increased loading resulted in decreased mechanical properties along the entire tendon length at both time points. Decreased loading resulted in both increased and decreased tendon properties at different regions of the tendon at 4 weeks, but by 8 weeks, there were no differences between decreased loading and detachment alone. We could not conclude where changes begin in the tendon with altered loading, but did demonstrate that regional differences exist. These results support that there is an effect of altered loading, as decreased loading resulted in variable changes at 4 weeks that were no different from detachment alone by 8 weeks, and increased loading resulted in detrimental properties along the entire length at both 4 and 8 weeks.     

The interface of mechanical loading and biological variables as they pertain to the development of tendinosis

Different tendons are designed to withstand different mechanical loads in their individual environments. Variable physiologic loading ranges and correspondingly different injury thresholds lead to tendon heterogeneity. Also, tendon heterogeneity is evident when examining how different tendons regulate their response to changes in mechanical loading (over- and under-loading). The response of tendons to changes in mechanical loading plays an important role in the induction and progression of tendinosis which is tendon degeneration without inflammation. Tendon overuse injury is likely related to abnormal mechanical loading that deviates from normal mechanical loading in magnitude, frequency, duration and/or direction. Mechanical loading that results in tendon overuse injury can initiate a repair process but, after failed initial repair, non-resolving chronic attempted repair appears to lead to a "smoldering" fibrogenesis. Contributions of regulatory components, including minor components in the "nerve-mast cell-myofibroblast axis", are key features in the development and progression of tendinosis. Hormonal and genetic factors may also influence risk for tendinosis. Further understanding of how tendinosis induction is related to mechanical use/overuse, how tendinosis progression is related to abnormal regulation of attempted repair, and how induction and/or progression are modulated by other risk factors may lead to interventions that mitigate risk and enhance functional repair.     

Tendon to bone healing: differences in biomechanical,structural, and compositional properties due to a range of activity levels

Little knowledge exists about the healing process of the tendon to bone insertion, and hence little can be done to improve tissue healing. The goal of this study is to describe the healing of the supraspinatus tendon to its bony insertion under a variety of loading conditions. Tendons were surgically detached and repaired in rats. Rat shoulders were then immobilized, allowed cage activity, or exercised. Shoulders that were immobilized demonstrated superior structural (significantly higher collagen orientation), compositional (expression of extracellular matrix genes similar to the uninjured insertion), and quasilinear viscoelastic properties (A = 0.30 +/- 0.10 MPa vs. 0.16 +/- 0.08 MPa, B = 17.4 +/- 2.9 vs. 15.1 +/- 0.9, and tau 2 = 344 +/- 161 s vs. 233 +/- 40 s) compared to those that were exercised, contrary to expectations. With this knowledge of the healing response, treatment modalities for rotator cuff tears can be developed.     

Tendon conditioning: artefact or property?

Isolated tendons subjected to cyclic tensile loads higher than those experienced in the tendons' recent history exhibit 'conditioning', i.e. gradually increasing elongations upon loading and gradually increasing residual elongations after unloading in the first few loading-unloading cycles. The present study examines whether this behaviour is a measurement artefact or an actual time-dependent property. The gastrocnemius tendons of six men who refrained from rigorous physical activities prior to the experiment were loaded cyclically by 10 repeated isometric plantarflexion contractions at 80% of the moment generated during plantarflexion maximal voluntary contraction (MVC). In each contraction, the elongation of the gastrocnemius tendon at 80% of MVC and the residual tendon elongation after relaxation were obtained from the analysis of sonographs recorded during the test. The tendon elongation during activation and the residual tendon elongation after relaxation increased by ca. 5 mm from the first contraction to the tenth contraction, with no changes obtained after the fifth contraction. The behaviour of the tendon in the first five contractions indicates the presence of conditioning. It is therefore concluded that conditioning is a relevant property and not an artefact associated with in vitro testing. This has implications for joint kinematics and muscle excursion.     

Expression of insulin-like growth factor I, insulin-like growth factor binding proteins, and collagen mRNA in mechanically loaded plantaris tendon.

Insulin-like growth factor I (IGF-I) is known to exert an anabolic effect on tendon fibroblast production of collagen. IGF-I's regulation is complex and involves six different IGF binding proteins (IGFBPs). Of these, IGFBP-4 and -5 could potentially influence the effect of IGF-I in the tendon because they both are produced in fibroblast; however, the response of IGFBP-4 and -5 to mechanical loading and their role in IGF-I regulation in tendinous tissue are unknown. A splice variant of IGF-I, mechano-growth factor (MGF) is upregulated and known to be important for adaptation in loaded muscle. However, it is not known whether MGF is expressed and upregulated in mechanically loaded tendon. This study examined the effect of mechanical load on tendon collagen mRNA in relation to changes in the IGF-I systems mRNA expression. Data were collected at 2, 4, 8 and 16 days after surgical removal of synergistic muscle to the plantaris muscle of the rat, thus increasing the load to plantaris muscle and tendon. Nearly a doubling of the tendon mass was observed after 16 days of loading. A rapid rise in tendon procollagen III mRNA was seen after 2 days whereas the increase in procollagen I mRNA was significant from day 8. MGF was expressed and upregulated in loaded tendon tissue with a faster response than IGF-I, which was increased from day 8. Finally, IGFBP-4 mRNA was increased with a time pattern similar to procollagen III, whereas IGFBP-5 decreased at day 8. In conclusion, loading of tendon tissue results in an upregulation of IGF-I, IGFBP-4, and procollagen and is associated with an increase in tendon mass. Also, MGF is expressed with an early upregulation in loaded tendon tissue. We suggest that the IGF-I system could be involved in collagen synthesis in tendon in response to mechanical loading.     

Effect of including damage at the tissue level in the nonlinear homogenisation of trabecular bone

Being able to predict bone fracture or implant stability needs a proper constitutive model of trabecular bone at the macroscale in multiaxial, non-monotonic loading modes. Its macroscopic damage behaviour has been investigated experimentally in the past, mostly with the restriction of uniaxial cyclic loading experiments for different samples, which does not allow for the investigation of several load cases in the same sample as damage in one direction may affect the behaviour in other directions. Homogenised finite element models of whole bones have the potential to assess complicated scenarios and thus improve clinical predictions. The aim of this study is to use a homogenisation-based multiscale procedure to upscale the damage behaviour of bone from an assumed solid phase constitutive law and investigate its multiaxial behaviour for the first time. Twelve cubic specimens were each submitted to nine proportional strain histories by using a parallel code developed in-house. Evolution of post-elastic properties for trabecular bone was assessed for a small range of macroscopic plastic strains in these nine load cases. Damage evolution was found to be non-isotropic, and both damage and hardening were found to depend on the loading mode (tensile, compression or shear); both were characterised by linear laws with relatively high coefficients of determination. It is expected that the knowledge of the macroscopic behaviour of trabecular bone gained in this study will help in creating more precise continuum FE models of whole bones that improve clinical predictions.     

The mechanical behaviour of brain tissue: large strain response and constitutive modelling

The non-linear mechanical behaviour of porcine brain tissue in large shear deformations is determined. An improved method for rotational shear experiments is used, producing an approximately homogeneous strain field and leading to an enhanced accuracy. Results from oscillatory shear experiments with a strain amplitude of 0.01 and frequencies ranging from 0.04 to 16 Hz are given. The immediate loss of structural integrity, due to large deformations, influencing the mechanical behaviour of brain tissue, at the time scale of loading, is investigated. No significant immediate mechanical damage is observed for these shear deformations up to strains of 0.45. Moreover, the material behaviour during complex loading histories (loading-unloading) is investigated. Stress relaxation experiments for strains up to 0.2 and constant strain rate experiments for shear rates from 0.01 to 1 s(-1) and strains up to 0.15 are presented. A new differential viscoelastic model is used to describe the mechanical response of brain tissue. The model is formulated in terms of a large strain viscoelastic framework and considers non-linear viscous deformations in combination with non-linear elastic behaviour. This constitutive model is readily applicable in three-dimensional head models in order to predict the mechanical response of the intra-cranial contents due to an impact.     

Age-related effect of static and cyclic loadings on the strain-force curve of the vastus lateralis tendon and aponeurosis

The objective of the present study was to investigate the age-related effects of submaximal static and cyclic loading on the mechanical properties of the vastus lateralis (VL) tendon and aponeurosis in vivo. Fourteen old and 12 young male subjects performed maximal voluntary isometric knee extensions (MVC) on a dynamometer before and after (a) a sustained isometric contraction at 25% MVC and (b) isokinetic contractions at 50% isokinetic MVC, both until task failure. The elongation of the VL tendon and aponeurosis was examined using ultrasonography. To calculate the resultant knee joint moment, the kinematics of the leg were recorded with eight cameras (120 Hz). The old adults displayed significantly lower maximal moments but higher strain values at any given tendon force from 400 N and up in all tested conditions. Neither of the loading protocols influenced the strain-force relationship of the VL tendon and aponeurosis in either the old or young adults. Consequently, the capacity of the tendon and aponeurosis to resist force remained unaffected in both groups. It can be concluded that in vivo tendons are capable of resisting long-lasting static (~4.6 min) or cyclic (~18.5 min) mechanical loading at the attained strain levels (4-5%) without significantly altering their mechanical properties regardless of age. This implies that as the muscle becomes unable to generate the required force due to fatigue, the loading of the tendon is terminated prior to provoking any significant changes in tendon mechanical properties.     

Influence of sensor size on the accuracy of in-vivo ligament and tendon force measurements.

In-vivo tendon forces are commonly measured using transducers, which detect tension in the tendon fibers. A poorly understood source of measurement errors is the difference in stress distribution within the tendon between experimental and transducer calibration conditions. The objective of this study was to investigate this source of error, and to determine whether these errors could be minimized by proper selection of transducer size. The study was conducted using the infrapatellar ligament (patellar tendon) of New Zealand White rabbits. Tendon force was measured with two different size implantable force transducers (IFTs), one Wide and one Narrow, and by a strain gaged load cell in series with the tendon. Tests were conducted at five different loading conditions selected to produce five different stress distributions within the tendon. One loading condition corresponded to a typical post-experiment calibration, and the data from that condition were used to develop a calibration equation for the transducer. The errors that resulted from using this calibration were determined by comparing the tendon force measured by the in-series load cell with the force predicted from the IFT output using the calibration equation. Changes in stress distribution produced measurement errors up to 64 N with the Narrow IFT but only 24 N with the Wide IFT. We found the measurement error was dependent on sensor width. Our results support the hypothesis that measurement errors can be caused by differences in tendon stress distribution between calibration and experimental conditions. We further showed that these errors can be minimized by using an IFT, which samples the tension in a large percentage of the tendon fibers. Information from this study can be used for selection of an appropriately sized implantable force transducer for measuring tendon and ligament force.     

A method to characterize in vivo tendon force-strain relationship by combining ultrasonography, motion capture and loading rates

The ultrasonography contributes to investigate in vivo tendon force-strain relationship during isometric contraction. In previous studies, different methods are available to estimate the tendon strain, using different loading rates and models to fit the tendon force-strain relationship. This study was aimed to propose a standard method to characterize the in vivo tendon force-strain relationship. We investigated the influence on the force-strain relationship for medialis gastrocnemius (MG) of (1) one method which takes into account probe and joint movements to estimate the instantaneous tendon length, (2) models used to fit the force-strain relationship for uniaxial test (polynomial vs. Ogden), and (3) the loading rate on tendon strain. Subjects performed ramp-up contraction during isometric contractions at two different target speeds: 1.5s and minimal time with ultrasound probe fixed over the muscle-tendon junction of the MG muscle. The used method requires three markers on ultrasound probe and a marker on calcaneum to take into account all movements, and was compared to the strain estimated using ultrasound images only. The method using ultrasound image only overestimated the tendon strain from 40% of maximal force. The polynomial model showed similar fitting results than the Ogden model (R2=0.98). A loading rate effect was found on tendon strain, showing a higher strain when loading rate decreases. The characterization of tendon force-strain relationship needs to be standardized by taking into account all movements to estimate tendon strain and controlling the loading rate. The polynomial model appears to be appropriate to represent the tendon force-strain relationship.     

The relationships between cyclic fatigue loading, changes in initial mechanical properties, and the in vivo temporal mechanical response of the rat patellar tendon

Damage accumulation underlies tendinopathy. Animal models of overuse injuries do not typically control loads applied to the tendon. Our in vivo model in the rat patellar tendon allows direct control of the loading applied to the tendon. Despite this advantage, natural variation among tendons results in different amounts of damage induced by the same loading protocol. Our objectives were to (1) assess changes in the initial mechanical parameters (hysteresis, stiffness of the loading and unloading load-displacement curves, and elongation) after fatigue loading to identify parameters that are indicative of the induced damage, and (2) evaluate the relationships between these identified initial damage indices with the stiffness 7 day after loading. Left patellar tendons of adult, female retired breeder, Sprague-Dawley rats (n = 68) were fatigue loaded per our previously published in vivo fatigue loading protocol. To induce a range of damage, fatigue loading consisted of either 5, 100, 500 or 7200 cycles that ranged from 1 N to 40 N. Diagnostic tests were applied before and immediately after fatigue loading, and after 45 min of recovery to deduce recoverable and non-recoverable changes in initial damage indices. Relationships between these initial damage indices and the 7-day stiffness (at sacrifice) were determined. Day-0 hysteresis, loading and unloading stiffness exhibited cycle-dependent changes. Initial hysteresis loss correlated with the 7-day stiffness. k-means cluster analysis demonstrated a relationship between 7-day stiffness and day-0 hysteresis and unloading stiffness. This analysis also separated samples that exhibited low from high damage in response to both high or low number of cycles; a key delineation for interpretation of the biological response in future studies. Identifying initial parameters that reflect the induced damage is critical since the ability of the tendon to repair depends on the damage induced and the number of applied loading cycles.     

Tenocyte contraction induces crimp formation in tendon-like tissue

Tendons are composed of longitudinally aligned collagen fibrils arranged in bundles with an undulating pattern, called crimp. The crimp structure is established during embryonic development and plays a vital role in the mechanical behaviour of tendon, acting as a shock-absorber during loading. However, the mechanism of crimp formation is unknown, partly because of the difficulties of studying tendon development in vivo. Here, we used a 3D cell culture system in which embryonic tendon fibroblasts synthesise a tendon-like construct comprised of collagen fibrils arranged in parallel bundles. Investigations using polarised light microscopy, scanning electron microscopy and fluorescence microscopy showed that tendon constructs contained a regular pattern of wavy collagen fibrils. Tensile testing indicated that this superstructure was a form of embryonic crimp producing a characteristic toe region in the stress–strain curves. Furthermore, contraction of tendon fibroblasts was the critical factor in the buckling of collagen fibrils during the formation of the crimp structure. Using these biological data, a finite element model was built that mimics the contraction of the tendon fibroblasts and monitors the response of the Extracellular matrix. The results show that the contraction of the fibroblasts is a sufficient mechanical impulse to build a planar wavy pattern. Furthermore, the value of crimp wavelength was determined by the mechanical properties of the collagen fibrils and inter-fibrillar matrix. Increasing fibril stiffness combined with constant matrix stiffness led to an increase in crimp wavelength. The data suggest a novel mechanism of crimp formation, and the finite element model indicates the minimum requirements to generate a crimp structure in embryonic tendon.     

Interphalangeal joint and tendon forces: normal model and biomechanical consequences of surgical reconstruction

Soft tissue reconstructive surgery for rheumatoid-related proximal interphalangeal joint deformities frequently fails to produce the long-term predicted results. Detailed information on the biomechanics of this joint, under both normal and pathological conditions, is required to assess the efficacy of such surgical intervention. A biomechanical model of the proximal interphalangeal joint has been developed to investigate tendon and joint loading during real life three-dimensional activities. Based on a rigid body mechanics approach, the model uses high resolution MRI scans to obtain anatomical tendon and bone geometries in conjunction with three-dimensional kinematic and loading data. The model incorporates an optimisation routine which minimises overall maximum tendon stress in the eight individual elements considered. Radial and ulnar joint force components are included at the proximal interphalangeal joint level. Two simulated pathological versions of the mathematical model are developed to accommodate the altered anatomic relationships after tendon reconstructive surgery. Joint forces of up to 450N and common usage of the extensor mechanism during normal pinching and grasping activities are predicted. The ulnar lateral bands of the extensor tendon are generally loaded to a greater extent than the radial bands. Extensor tendon and joint forces in the simulated pathological models are significantly higher than those in the normal model. Combined with the poor tendon quality of rheumatoid arthritis patients generally, these amplified internal forces may lead to further joint deformation.     

Effect of partial-thickness tear on loading capacities of the supraspinatus tendon: a finite element analysis

Partial-thickness tears of the supraspinatus tendon frequently occur at its insertion on the greater tubercule of the humerus, causing pain and reduced strength and range of motion. The goal of this work was to quantify the loss of loading capacity due to tendon tears at the insertion area. A finite element model of the supraspinatus tendon was developed using in vivo magnetic resonance images data. The tendon was represented by an anisotropic hyperelastic constitutive law identified with experimental measurements. A failure criterion was proposed and calibrated with experimental data. A partial-thickness tear was gradually increased, starting from the deep articular-sided fibres. For different values of tendon tear thickness, the tendon was mechanically loaded up to failure. The numerical model predicted a loss in loading capacity of the tendon as the tear thickness progressed. Tendon failure was more likely when the tendon tear exceeded 20%. The predictions of the model were consistent with experimental studies. Partial-thickness tears below 40% tear are sufficiently stable to persist physiotherapeutic exercises. Above 60% tear surgery should be considered to restore shoulder strength.     

Mechanobiology of tendon

Tendons are able to respond to mechanical forces by altering their structure, composition, and mechanical properties--a process called tissue mechanical adaptation. The fact that mechanical adaptation is effected by cells in tendons is clearly understood; however, how cells sense mechanical forces and convert them into biochemical signals that ultimately lead to tendon adaptive physiological or pathological changes is not well understood. Mechanobiology is an interdisciplinary study that can enhance our understanding of mechanotransduction mechanisms at the tissue, cellular, and molecular levels. The purpose of this article is to provide an overview of tendon mechanobiology. The discussion begins with the mechanical forces acting on tendons in vivo, tendon structure and composition, and its mechanical properties. Then the tendon's response to exercise, disuse, and overuse are presented, followed by a discussion of tendon healing and the role of mechanical loading and fibroblast contraction in tissue healing. Next, mechanobiological responses of tendon fibroblasts to repetitive mechanical loading conditions are presented, and major cellular mechanotransduction mechanisms are briefly reviewed. Finally, future research directions in tendon mechanobiology research are discussed.     

Finite element model of subsynovial connective tissue deformation due to tendon excursion in the human carpal tunnel

Carpal tunnel syndrome (CTS) is a nerve entrapment disease, which has been extensively studied by the engineering and medical community. Although the direct cause is unknown, in vivo and in vitro medical research has shown that tendon excursion creates microtears in the subsynovial connective tissue (SSCT) surrounding the tendon in the carpal tunnel. One proposed mechanism for the SSCT injury is shearing, which is believed to cause fibrosis of the SSCT. Few studies have reported quantitative observations of SSCT response to mechanical loading. Our proposed model is a 2-D section that consists of an FDS tendon, interstitial SSCT and adjacent stationary tendons. We believe that developing this model will allow the most complete quantitative observations of SSCT response to mechanical loading reported thus far. Boundary conditions were applied to the FEA model to simulate single finger flexion. A velocity was applied to the FDS tendon in the model to match loading conditions of the documented cadaver wrist kinematics studies. The cadaveric and FEA displacement results were compared to investigate the magnitude of stiffness required for the SSCT section of the model. The relative motions between the model and cadavers matched more closely than the absolute displacements. Since cadaveric models do not allow identification of the SSCT layers, an FEA model will help determine the displacement and stress experienced by each SSCT layer. Thus, we believe this conceptual model is a first step in understanding how the SSCT layers are recruited during tendon excursion.     

In vivo investigation of tendon responses to mechanical loading

Tendons transmit skeletal muscle forces to bone and are essential in all voluntary movement. In turn, movement appears to affect tendon properties, and in recent years considerable effort has been put into discovering how tendon tissue responds to mechanical stimuli in vivo. Months and years of mechanical loading can influence the gross morphology of tendon, seen as an increase tendon cross sectional area (CSA). Similarly, tendon stiffness appears to be affected by weeks to months of loading. Increased stiffness can relate to changes in CSA and/or tendon material properties (modulus), though the relative contribution of these parameters is largely unclear. The possible mechanisms behind alterations in tendon material properties include changes in collagen fibril morphology and levels of cross-linking between collagen molecules. Furthermore, increased levels of collagen synthesis and expression are seen as a response to acute exercise and training, and may be a central parameter in tendon adaptation to loading. There are indications that this collagen-induction relates to the auto-/paracrine action of collagen-stimulating growth factors, such as TGFβ-1 and IGF-I, which are expressed in response to mechanical stimuli.     

Implementation and validation of probabilistic models of the anterior longitudinal ligament and posterior longitudinal ligament of the cervical spine

The objective of this investigation was to develop probabilistic finite element (FE) models of the anterior longitudinal ligament (ALL) and posterior longitudinal ligament (PLL) of the cervical spine that incorporate the natural variability of biological specimens. In addition to the model development, a rigorous validation methodology was developed to quantify model performance. Experimental data for the geometry and dynamic properties of the ALL and PLL were used to create probabilistic FE models capable of predicting not only the mean dynamic relaxation response but also the observed experimental variation of that response. The probabilistic FE model uses a quasilinear viscoelastic material constitutive model to capture the time-dependent behaviour of the ligaments. The probabilistic analysis approach yields a statistical distribution for the model-predicted response at each time point rather than a single deterministic quantity (e.g. ligament force) and that response can be statistically compared to experimental data for validation. A quantitative metric that compares the cumulative distribution functions of the experimental data and model response is computed for both the ALL and PLL throughout the time histories and is used to quantify model performance.     

In vivo forces generated by finger flexor muscles do not depend on the rate of fingertip loading during an isometric task

Risk factors for activity-related tendon disorders of the hand include applied force, duration, and rate of loading. Understanding the relationship between external loading conditions and internal tendon forces can elucidate their role in injury and rehabilitation. The goal of this investigation is to determine whether the rate of force applied at the fingertip affects in vivo forces in the flexor digitorum profundus (FDP) tendon and the flexor digitorum superficialis (FDS) tendon during an isometric task. Tendon forces, recorded with buckle force transducers, and fingertip forces were simultaneously measured during open carpal tunnel surgery as subjects (N=15) increased their fingertip force from 0 to 15N in 1, 3, and 10s. The rates of 1.5, 5, and 15N/s did not significantly affect FDP or FDS tendon to fingertip force ratios. For the same applied fingertip force, the FDP tendon generated more force than the FDS. The mean FDP to fingertip ratio was 2.4+/-0.7 while the FDS to tip ratio averaged 1.5+/-1.0 (p<0.01). The fine motor control needed to generate isometric force ramps at these specific loading rates probably required similar high activation levels of multiple finger muscles in order to stabilize the finger and control joint torques at the force rates studied. Therefore, for this task, no additional increase in muscle force was observed at higher rates. These findings suggest that for high precision, isometric pinch maneuvers under static finger conditions, tendon forces are independent of loading rate.