Distal hamstrings tendons mechanical properties at rest and contraction using free-hand 3-D ultrasonography.

Tendon properties impact human locomotion, influencing sports performance, and injury prevention. Hamstrings play a crucial role in sprinting, particularly the biceps femoris long head (BFlh), which is prone to frequent injuries. It remains uncertain if BFlh exhibits distinct mechanical properties compared to other hamstring muscles. This study utilized free-hand three-dimensional ultrasound to assess morphological and mechanical properties of distal hamstrings tendons in 15 men. Scans were taken in prone position, with hip and knee extended, at rest and during 20%, 40%, 60%, and 80% of maximal voluntary isometric contraction of the knee flexors. Tendon length, volume, cross-sectional area (CSA), and anteroposterior (AP) and mediolateral (ML) widths were quantified at three locations. Longitudinal and transverse deformations, stiffness, strain, and stress were estimated. The ST had the greatest tendon strain and the lowest stiffness as well as the highest CSA and AP and ML width strain compared to other tendons. Biceps femoris short head (BFsh) exhibited the least strain, AP and ML deformation. Further, BFlh displayed the highest stiffness and stress, and BFsh had the lowest stress. Additionally, deformation varied by region, with the proximal site showing generally the lowest CSA strain. Distal tendon mechanical properties differed among the hamstring muscles during isometric knee flexions. In contrast to other bi-articular hamstrings, the BFlh high stiffness and stress may result in greater energy absorption by its muscle fascicles, rather than the distal tendon, during late swing in sprinting. This could partly account for the increased incidence of hamstring injuries in this muscle.

Aged Tendons Exhibit Altered Mechanisms of Strain-Dependent Extracellular Matrix Remodeling.

Aging is a primary risk factor for degenerative tendon injuries, yet the etiology and progression of this degeneration are poorly understood. While aged tendons have innate cellular differences that support a reduced ability to maintain mechanical tissue homeostasis, the response of aged tendons to altered levels of mechanical loading has not yet been studied. To address this question, we subjected young and aged murine flexor tendon explants to various levels of in vitro tensile strain. We first compared the effect of static and cyclic strain on matrix remodeling in young tendons, finding that cyclic strain is optimal for studying remodeling in vitro. We then investigated the remodeling response of young and aged tendon explants after 7 days of varied mechanical stimulus (stress deprivation, 1%, 3%, 5%, or 7% cyclic strain) via assessment of tissue composition, biosynthetic capacity, and degradation profiles. We hypothesized that aged tendons would show muted adaptive responses to changes in tensile strain and exhibit a shifted mechanical setpoint, at which the remodeling balance is optimal. Interestingly, we found that 1% cyclic strain best maintains native physiology while promoting extracellular matrix (ECM) turnover for both age groups. However, aged tendons display fewer strain-dependent changes, suggesting a reduced ability to adapt to altered levels of mechanical loading. This work has a significant impact on understanding the regulation of tissue homeostasis in aged tendons, which can inform clinical rehabilitation strategies for treating elderly patients.

Effects of gait retraining using minimalist shoes on the medial gastrocnemius muscle-tendon unit behavior and dynamics during running.

The effects of a 12-week gait retraining program on the adaptation of the medial gastrocnemius (MG) and muscle-tendon unit (MTU) were investigated. 26 runners with a rearfoot strike pattern (RFS) were randomly assigned to one of two groups: gait retraining (GR) or control group (CON). MG ultrasound images, marker positions, and ground reaction forces (GRF) were collected twice during 9 km/h of treadmill running before and after the intervention. Ankle kinetics and the MG and MTU behavior and dynamics were quantified. Runners in the GR performed gradual 12-week gait retraining transitioning to a forefoot strike pattern. After 12-week, (1) ten participants in each group completed the training; eight participants in GR transitioned to non-RFS with reduced foot strike angles; (2) MG fascicle contraction length and velocity significantly decreased after the intervention for both groups, whereas MG forces increased after intervention for both groups; (3) significant increases in MTU stretching length for GR and peak MTU recoiling velocity for both groups were observed after the intervention, respectively; (4) no significant difference was found for all parameters of the series elastic element. Gait retraining might potentially influence the MG to operate at lower fascicle contraction lengths and velocities and produce greater peak forces. The gait retraining had no effect on SEE behavior and dynamics but did impact MTU, suggesting that the training was insufficient to induce mechanical loading changes on SEE behavior and dynamics.

Engineering Tendon Assembloids to Probe Cellular Crosstalk in Disease and Repair.

Tendons enable locomotion by transferring muscle forces to bones. They rely on a tough tendon core comprising collagen fibers and stromal cell populations. This load-bearing core is encompassed, nourished, and repaired by a synovial-like tissue layer comprising the extrinsic tendon compartment. Despite this sophisticated design, tendon injuries are common, and clinical treatment still relies on physiotherapy and surgery. The limitations of available experimental model systems have slowed the development of novel disease-modifying treatments and relapse-preventing clinical regimes. In vivo human studies are limited to comparing healthy tendons to end-stage diseased or ruptured tissues sampled during repair surgery and do not allow the longitudinal study of the underlying tendon disease. In vivo animal models also present important limits regarding opaque physiological complexity, the ethical burden on the animals, and large economic costs associated with their use. Further, in vivo animal models are poorly suited to systematic probing of drugs and multicellular, multi-tissue interaction pathways. Simpler in vitro model systems have also fallen short. One major reason is a failure to adequately replicate the three-dimensional mechanical loading necessary to meaningfully study tendon cells and their function. The new 3D model system presented here alleviates some of these issues by exploiting murine tail tendon core explants. Importantly, these explants are easily accessible in large numbers from a single mouse, retain 3D in situ loading patterns at the cellular level, and feature an in vivo-like extracellular matrix. In this protocol, step-by-step instructions are given on how to augment tendon core explants with collagen hydrogels laden with muscle-derived endothelial cells, tendon-derived fibroblasts, and bone marrow-derived macrophages to substitute disease- and injury-activated cell populations within the extrinsic tendon compartment. It is demonstrated how the resulting tendon assembloids can be challenged mechanically or through defined microenvironmental stimuli to investigate emerging multicellular crosstalk during disease and injury.

Assessment and modelling of the activation-dependent shift in optimal length of the human soleus muscle in vivo.

Previous in vitro and in situ studies have reported a shift in optimal muscle fibre length for force generation (L0) towards longer length at decreasing activation levels (also referred to as length-dependent activation), yet the relevance for in vivo human muscle contractions with a variable activation pattern remains largely unclear. By a combination of dynamometry, ultrasound and electromyography (EMG), we experimentally obtained muscle force-fascicle length curves of the human soleus at 100%, 60% and 30% EMGmax levels from 15 participants aiming to investigate activation-dependent shifts in L0 in vivo. The results showed a significant increase in L0 of 6.5 ± 6.0% from 100% to 60% EMGmax and of 9.1 ± 7.2% from 100% to 30% EMGmax (both P < 0.001), respectively, providing evidence of a moderate in vivo activation dependence of the soleus force-length relationship. Based on the experimental results, an approximation model of an activation-dependent force-length relationship was defined for each individual separately and for the collective data of all participants, both with sufficiently high accuracy (R2 of 0.899 ± 0.056 and R2 = 0.858). This individual approximation approach and the general approximation model outcome are freely accessible and may be used to integrate activation-dependent shifts in L0 in experimental and musculoskeletal modelling studies to improve muscle force predictions. KEY POINTS: The phenomenon of the activation-dependent shift in optimal muscle fibre length for force generation (length-dependent activation) is poorly understood for human muscle in vivo dynamic contractions. We experimentally observed a moderate shift in optimal fascicle length towards longer length at decreasing electromyographic activity levels for the human soleus muscle in vivo. Based on the experimental results, we developed a freely accessible approximation model that allows the consideration of activation-dependent shifts in optimal length in future experimental and musculoskeletal modelling studies to improve muscle force predictions.

Janus Membranes Patch Achieves High-Quality Tendon Repair: Inhibiting Exogenous Healing and Promoting Endogenous Healing.

The imbalance between endogenous and exogenous healing is the fundamental reason for the poor tendon healing. In this study, a Janus patch was developed to promote endogenous healing and inhibit exogenous healing, leading to improved tendon repair. The upper layer of the patch is a poly(dl-lactide-co-glycolide)/polycaprolactone (PLGA/PCL) nanomembrane (PMCP-NM) modified with poly(2-methylacryloxyethyl phosphocholine) (PMPC), which created a lubricated and antifouling surface, preventing cell invasion and mechanical activation. The lower layer is a PLGA/PCL fiber membrane loaded with fibrin (Fb) (Fb-NM), serving as a temporary chemotactic scaffold to regulate the regenerative microenvironment. In vitro, the Janus patch effectively reduced 92.41% cell adhesion and 79.89% motion friction. In vivo, the patch inhibited tendon adhesion through the TGF-ß/Smad signaling pathway and promoted tendon maturation. This Janus patch is expected to provide a practical basis and theoretical guidance for high-quality soft tissue repair.

Combined Effects of Static and Dynamic Stretching on the Muscle-Tendon Unit Stiffness and Strength of the Hamstrings.

ABSTRACT: Takeuchi, K, Nakamura, M, Matsuo, S, Samukawa, M, Yamaguchi, T, and Mizuno, T. Combined effects of static and dynamic stretching on the muscle-tendon unit stiffness and strength of the hamstrings. J Strength Cond Res 38(4): 681-686, 2024-Combined static and dynamic stretching for 30 seconds is frequently used as a part of a warm-up program. However, a stretching method that can both decrease muscle-tendon unit (MTU) stiffness and increase muscle strength has not been developed. The purpose of this study was to examine the combined effects of 30 seconds of static stretching at different intensities (normal-intensity static stretching [NS] and high-intensity static [HS]) and dynamic stretching at different speeds (low-speed dynamic [LD] and high-speed dynamic stretching [HD]) on the MTU stiffness and muscle strength of the hamstrings. Thirteen healthy subjects (9 men and 4 women, 20.9 ± 0.8 years, 169.3 ± 7.2 cm, 61.1 ± 8.2 kg) performed 4 types of interventions (HS-HD, HS-LD, NS-HD, and NS-LD). Range of motion (ROM), passive torque, MTU stiffness, and muscle strength were measured before and immediately after interventions by using an isokinetic dynamometer machine. In all interventions, the ROM and passive torque significantly increased (p < 0.01). Muscle-tendon unit stiffness significantly decreased in HS-HD and HS-LD (both p < 0.01), but there was no significant change in NS-HD (p = 0.30) or NS-LD (p = 0.42). Muscle strength significantly increased after HS-HD (p = 0.02) and NS-LD (p = 0.03), but there was no significant change in HS-LD (p = 0.23) or NS-LD (p = 0.26). The results indicated that using a combination of 30 seconds of high-intensity static stretching and high-speed dynamic stretching can be beneficial for the MTU stiffness and muscle strength of the hamstrings.

Eccentric exercise ≠ eccentric contraction.

Whether eccentric exercise involves active fascicle stretch is unclear due to muscle-tendon unit (MTU) series compliance. Therefore, this study investigated the impact of changing the activation timing and level (i.e., preactivation) of the contraction on muscle fascicle kinematics and kinetics of the human tibialis anterior during dynamometer-controlled maximal voluntary MTU-stretch-hold contractions. B-mode ultrasound and surface electromyography were used to assess muscle fascicle kinematics and muscle activity levels, respectively. Although joint kinematics were similar among MTU-stretch-hold contractions (∼40° rotation amplitude), increasing preactivation increased fascicle shortening and stretch amplitudes (9.9-23.2 mm, P ≤ 0.015). This led to increasing positive and negative fascicle work with increasing preactivation. Despite significantly different fascicle kinematics, similar peak fascicle forces during stretch occurred at similar fascicle lengths and joint angles regardless of preactivation. Similarly, residual force enhancement (rFE) following MTU stretch was not significantly affected (6.5-7.6%, P = 0.559) by preactivation, but rFE was strongly correlated with peak fascicle force during stretch (rrm = 0.62, P = 0.003). These findings highlight that apparent eccentric exercise causes shortening-stretch contractions at the fascicle level rather than isolated eccentric contractions. The constant rFE despite different fascicle kinematics and kinetics suggests that a passive element was engaged at a common muscle length among conditions (e.g., optimal fascicle length). Although it remains unclear whether different fascicle mechanics trigger different adaptations to eccentric exercise, this study emphasizes the need to consider MTU series compliance to better understand the mechanical drivers of adaptation to exercise.NEW & NOTEWORTHY Apparent eccentric exercises do not result in isolated eccentric contractions, but shortening-stretch contractions at the fascicle level. The amount of fascicle shortening and stretch depends on the preactivation during the exercise and cannot be estimated from the muscle-tendon unit (MTU) or joint kinematics. As different fascicle mechanics might trigger different adaptations to eccentric exercise, muscle-tendon unit series compliance and muscle preactivation need to be considered when eccentric exercise protocols are designed.

Immunomodulatory multicellular scaffolds for tendon-to-bone regeneration.

Limited motor activity due to the loss of natural structure impedes recovery in patients suffering from tendon-to-bone injury. Conventional biomaterials focus on strengthening the regenerative ability of tendons/bones to restore natural structure. However, owing to ignoring the immune environment and lack of multi-tissue regenerative function, satisfactory outcomes remain elusive. Here, combined manganese silicate (MS) nanoparticles with tendon/bone-related cells, the immunomodulatory multicellular scaffolds were fabricated for integrated regeneration of tendon-to-bone. Notably, by integrating biomimetic cellular distribution and MS nanoparticles, the multicellular scaffolds exhibited diverse bioactivities. Moreover, MS nanoparticles enhanced the specific differentiation of multicellular scaffolds via regulating macrophages, which was mainly attributed to the secretion of PGE2 in macrophages induced by Mn ions. Furthermore, three animal results indicated that the scaffolds achieved immunomodulation, integrated regeneration, and function recovery at tendon-to-bone interfaces. Thus, the multicellular scaffolds based on inorganic biomaterials offer an innovative concept for immunomodulation and integrated regeneration of soft/hard tissue interfaces.

Acute effects of resistance training at different range of motions on plantar flexion mechanical properties and force.

The effects obtained from resistance training depend on the exercise range of motion (ROM) performed. We aimed to examine the acute effects of different exercise ROM resistance training on the plantar flexor muscles. Eighteen healthy untrained male adults participated in three conditions: calf raises in 1) partial condition [final (short muscle length) partial ROM], 2) full condition (full ROM), and 3) control condition. The ankle dorsiflexion (DF) ROM, passive torque at DF ROM, passive stiffness of muscle-tendon unit, and maximal voluntary isometric contraction (MVC-ISO) torque were measured before and immediately after the interventions. There were significant increases in DF ROM, passive torque at DF ROM, and a decrease in MVC-ISO, but no significant interaction in passive stiffness. Post hoc test, DF ROM demonstrated moderate magnitude increases in the full condition compared to the partial (p = 0.023, d = 0.74) and control (p = 0.003, d = 0.71) conditions. Passive torque at DF ROM also showed moderate magnitude increases in the full condition compared to the control condition (p = 0.016, d = 0.69). MVC-ISO had a moderate magnitude decrease in the full condition compared to the control condition (p = 0.018, d=-0.53). Resistance training in the full ROM acutely increases joint ROM to a greater extent than final partial ROM, most likely due to stretch tolerance.

The interaction of in vivo muscle operating lengths and passive stiffness in rat hindlimbs.

The operating length of a muscle is a key determinant of its ability to produce force in vivo. Muscles that operate near the peak of their force-length relationship will generate higher forces whereas muscle operating at relatively short length may be safe from sudden lengthening perturbations and subsequent damage. At longer lengths, passive mechanical properties have the potential to contribute to force or constrain operating length with stiffer muscle-tendon units theoretically being restricted to shorter lengths. Connective tissues typically increase in density during aging, thus increasing passive muscle stiffness and potentially limiting the operating lengths of muscle during locomotion. Here, we compare in vivo and in situ muscle strain from the medial gastrocnemius in young (7 months old) and aged (30-32 months old) rats presumed to have varying passive tissue stiffness to test the hypothesis that stiffer muscles operate at shorter lengths relative to their force-length relationship. We measured in vivo muscle operating length during voluntary locomotion on inclines and flat trackways and characterized the muscle force-length relationship of the medial gastrocnemius using fluoromicrometry. Although no age-related results were evident, rats of both age groups demonstrated a clear relationship between passive stiffness and in vivo operating length, such that shorter operating lengths were significantly correlated with greater passive stiffness. Our results suggest that increased passive stiffness may restrict muscles to operating lengths shorter than optimal lengths, potentially limiting force capacity during locomotion.

Residual force depression is not related to positive muscle fascicle work during submaximal voluntary dorsiflexion contractions in humans.

Residual force depression (rFD) following active muscle shortening is assumed to correlate most strongly with muscle work, but this has not been tested during voluntary contractions in humans. Using dynamometry, we compared steady-state ankle joint torques (N = 16) following tibialis anterior (TA) muscle-tendon unit (MTU) lengthening and shortening to the time-matched torque during submaximal voluntary fixed-end dorsiflexion reference contractions (REF) at a matched MTU length and EMG amplitude. Ultrasound revealed significantly reduced (P < 0.001) TA fascicle shortening amplitudes during MTU lengthening without a preload over small and medium amplitudes, respectively, relative to REF. MTU lengthening with a preload over a large amplitude significantly (P < 0.001) increased fascicle shortening relative to REF, as well as stretch amplitudes relative to MTU lengthening without a preload (P = 0.001). Significant (P = 0.028) steady-state fascicle force enhancement relative to REF was observed following MTU lengthening, and was similar among MTU lengthening-hold conditions (3-5%). MTU shortening with and without a preload over small and large amplitudes significantly (P < 0.001) increased positive fascicle and MTU work relative to REF, but significant (P = 0.006) rFD was observed following MTU shortening with a preload (7-10%) only. rFD was linearly related to positive MTU work [rrm (47) = 0.48, P < 0.001], but not positive fascicle work [rrm (47) = 0.16, P = 0.277]. Our findings indicate that MTU lengthening without substantial fascicle stretch enhances steady-state force output, which might arise from less shortening-induced rFD. Our findings also indicate similar rFD following different amounts of positive fascicle/MTU work, which cautions against using work to predict rFD during submaximal voluntary contractions. KEY POINTS: Accurately predicting muscle force is challenging because active muscle shortening depresses force output. The residual force depression (rFD) that exists following active muscle shortening is commonly assumed to correlate strongly and positively with muscle work. We found that tibialis anterior muscle fascicle work and muscle-tendon unit work did not accurately predict rFD during submaximal voluntary dorsiflexion contractions. Fascicle shortening during fixed-end reference contractions also potentially induced rFD of 3-5%, which was similar to the rFD following muscle-tendon unit shortening without a preload. A higher number of active muscle fibres during shortening probably increased rFD, which suggests that motor unit recruitment during shortening might predict rFD.

Static versus dynamic muscle modelling in extinct species: a biomechanical case study of the Australopithecus afarensis pelvis and lower extremity.

The force a muscle generates is dependent on muscle structure, in which fibre length, pennation angle and tendon slack length all influence force production. Muscles are not preserved in the fossil record and these parameters must be estimated when constructing a musculoskeletal model. Here, we test the capability of digitally reconstructed muscles of the Australopithecus afarensis model (specimen AL 288-1) to maintain an upright, single-support limb posture. Our aim was to ascertain the influence that different architectural estimation methods have on muscle specialisation and on the subsequent inferences that can be extrapolated about limb function. Parameters were estimated for 36 muscles in the pelvis and lower limb and seven different musculoskeletal models of AL 288-1 were produced. These parameters represented either a 'static' Hill-type muscle model (n = 4 variants) which only incorporated force, or instead a 'dynamic' Hill-type muscle model with an elastic tendon and fibres that could vary force-length-velocity properties (n = 3 variants). Each muscle's fibre length, pennation angle, tendon slack length and maximal isometric force were calculated based upon different input variables. Static (inverse) simulations were computed in which the vertical and mediolateral ground reaction forces (GRF) were incrementally increased until limb collapse (simulation failure). All AL 288-1 variants produced somewhat similar simulated muscle activation patterns, but the maximum vertical GRF that could be exerted on a single limb was not consistent between models. Three of the four static-muscle models were unable to support >1.8 times body weight and produced models that under-performed. The dynamic-muscle models were stronger. Comparative results with a human model imply that similar muscle group activations between species are needed to sustain single-limb support at maximally applied GRFs in terms of the simplified static simulations (e.g., same walking pose) used here. This approach demonstrated the range of outputs that can be generated for a model of an extinct individual. Despite mostly comparable outputs, the models diverged mostly in terms of strength.

Local vibration induces changes in spinal and corticospinal excitability in vibrated and antagonist muscles.

Local vibration (LV) applied over the muscle tendon constitutes a powerful stimulus to activate the muscle spindle primary (Ia) afferents that project to the spinal level and are conveyed to the cortical level. This study aimed to identify the neuromuscular changes induced by a 30-min LV-inducing illusions of hand extension on the vibrated flexor carpi radialis (FCR) and the antagonist extensor carpi radialis (ECR) muscles. We studied the change of the maximal voluntary isometric contraction (MVIC, experiment 1) for carpal flexion and extension, motor-evoked potentials (MEPs, experiment 2), cervicomedullary motor-evoked potentials (CMEPs, experiment 2), and Hoffmann's reflex (H-reflex, experiment 3) for both muscles at rest. Measurements were performed before (PRE) and at 0, 30, and 60 min after LV protocol. A lasting decrease in strength was only observed for the vibrated muscle. The reduction in CMEPs observed for both muscles seems to support a decrease in alpha motoneurons excitability. In contrast, a slight decrease in MEPs responses was observed only for the vibrated muscle. The MEP/CMEP ratio increase suggested greater cortical excitability after LV for both muscles. In addition, the H-reflex largely decreased for the vibrated and the antagonist muscles. The decrease in the H/CMEP ratio for the vibrated muscle supported both pre- and postsynaptic causes of the decrease in the H-reflex. Finally, LV-inducing illusions of movement reduced alpha motoneurons excitability for both muscles with a concomitant increase in cortical excitability.NEW & NOTEWORTHY Spinal disturbances confound the interpretation of excitability changes in motor areas and compromise the conclusions reached by previous studies using only a corticospinal marker for both vibrated and antagonist muscles. The time course recovery suggests that the H-reflex perturbations for the vibrated muscle do not only depend on changes in alpha motoneurons excitability. Local vibration induces neuromuscular changes in both vibrated and antagonist muscles at the spinal and cortical levels.

Contributions of collagen and elastin to elastic behaviours of tendon fascicle.

Tendon exhibits the capacity to be stretched and to return to its original length without suffering structural damage in vivo, a capacity known as elastic recoil. Collagen fibres are aligned longitudinally and elastin fibres mostly run parallel to collagen fibres in tendon. However, their interactions and contributions to tendon elastic behaviours are not well understood. The present study examined functional roles of collagen and elastin in tendon elastic behaviours using a variety of mechanical tests. We prepared three types of fascicle specimens from mouse tail tendon: fascicles freshly isolated, those digested with elastase in PBS to selectively remove elastin, and those incubated in PBS without elastase. A quasi-static tensile test demonstrated that elastase-treated fascicles had higher tangent moduli and strength compared to fresh and PBS fascicles. Cyclic stretching tests showed that fresh and PBS fascicles could withstand cyclic strain at both small and large amplitudes, but elastase-treated fascicles could only behave elastically to a limited degree. Fibre-sliding analysis revealed that fresh fascicles could be elongated both through stretching of collagen fibers and through movement of the fibres. However, elastase-treated fascicles could be stretched only via fibre stretching. This evidence suggests that normal tendons can be extended through both fibre stretching and fibre sliding, whereas tendons without elastin can only extend as much as collagen fibers can withstand. Accordingly, collagen fibres mainly contribute to tendon elastic behaviours by furnishing rigidity and elasticity, whereas elastin provides tendon viscoelasticity and also enables sliding of collagen fibres during elastic behaviours. STATEMENT OF SIGNIFICANCE: The present study revealed distinct mechanical functions of collagen and elastin fibres in elastic behaviours of mouse tail tendon fascicle using a variety of mechanical tests at both microscopic and macroscopic levels. It was demonstrated that collagen mainly governs tendon fascicle rigidity and elasticity, but only possesses limited extensibility, whereas elastin contributes to viscoelasticity and collagen fibre sliding, enabling elastic recoil behaviour against relatively large deformation. By their interactions, tendon can be elongated without suffering major structural damage and withstand a large magnitude of tensile force in response to mechanical loading. Such information should be particularly useful in designing collagen-based biomaterials such as artificial tendons, in that previous studies have merely considered collagen without incorporation of elastin.

Electron Beam-Modified Collagen Type I Fibers: Synthesis and Characterization of Mechanical Response.

Ten MeV electron beam treatment facilitates a biomimetic introduction of cross-links in collagenous biopolymer systems, modifying their viscoelastic properties, mechanical stability, and swelling behavior. For reconstituted collagen type I fibers, electron-induced cross-linking opens up new perspectives regarding future biomedical applications in terms of tissue and ligament engineering. We demonstrate how electron irradiation affects stiffness both in low-strain regimes and in postyield regimes of biocompatible reconstituted rat tail collagen type I fibers. Stress-strain tests show a dose-dependent increase in modulus in the nonlinear elastic response, indicating a central role of induced cross-links in mechanical stability. Environmental scanning electron microscopy after fiber rupture reveals aligned distributed collagen fibril domains under the fiber surface for as-prepared fibers, accompanied by a ductile fracture behavior, whereas, in tensile tests imaged by light microscopy after 10 MeV electron treatment, isotropic network topologies are observed until the occurrence of a brittle type of rupture. Based on the biomimicry of the process, these findings might pave the way for a novel type of synthesis of tailored tendon or ligament substitutes.

Muscle-Tendon Unit Length Measurement Using 3D Ultrasound in Passive Conditions: OpenSim Validation and Development of Personalized Models.

This study investigated the validity of using OpenSim to measure muscle-tendon unit (MTU) length of the bi-articular lower limb muscles in several postures (shortened, lengthened, a combination of shortened and lengthened involving both joints, neutral and standing) using 3D freehand ultrasound (US), and to propose new personalized models. MTU length was measured on 14 participants and 6 bi-articular muscles (semimembranosus SM, semitendinosus ST, biceps femoris BF, rectus femoris RF, gastrocnemius medialis GM and gastrocnemius lateralis GL), considering 5 to 6 postures. MTU length was computed using OpenSim with three different models: OS (the generic OpenSim scaled model), OS + INSER (OS with personalized 3D US MTU insertions), OS + INSER + PATH (OS with personalized 3D US MTU insertions and path obtained from one posture). Significant differences in MTU length were found between OS and 3D US models for RF, GM and GL (from - 6.3 to 10.9%). Non-significant effects were reported for the hamstrings, notably for the ST (- 1.5%) and BF (- 1.9%), while the SM just crossed the alpha level (- 3.4%, p = 0.049). The OS + INSER model reduced the magnitude of bias by an average of 4% for RF, GM and GL. The OS + INSER + PATH model showed the smallest biases in length estimates, which made them negligible and non-significant for all the MTU (i.e. ≤ 2.2%). A 3D US pipeline was developed and validated to estimate the MTU length from a limited number of measurements. This opens up new perspectives for personalizing musculoskeletal models using low-cost user-friendly devices.

The Simultaneous Model-Based Estimation of Joint, Muscle, and Tendon Stiffness is Highly Sensitive to the Tendon Force-Strain Relationship.

OBJECTIVE: Accurate estimation of stiffness across anatomical levels (i.e., joint, muscle, and tendon) in vivo has long been a challenge in biomechanics. Recent advances in electromyography (EMG)-driven musculoskeletal modeling have allowed the non-invasive estimation of stiffness during dynamic joint rotations. Nevertheless, validation has been limited to the joint level due to a lack of simultaneous in vivo experimental measurements of muscle and tendon stiffness. METHODS: With a focus on the triceps surae, we employed a novel perturbation-based experimental technique informed by dynamometry and ultrasonography to derive reference stiffness at the joint, muscle, and tendon levels simultaneously. Here, we propose a new EMG-driven model-based approach that does not require external joint perturbation, nor ultrasonography, to estimate multi-level stiffness. We present a novel set of closed-form equations that enables the person-specific tuning of musculoskeletal parameters dictating biological stiffness, including passive force-length relationships in modeled muscles and tendons. RESULTS: Calibrated EMG-driven musculoskeletal models estimated the reference data with average normalized root-mean-square error ≈ 20%. Moreover, only when calibrated tendons were approximately four times more compliant than typically modeled, our approach could estimate multi-level reference stiffness. CONCLUSION: EMG-driven musculoskeletal models can be calibrated on a larger set of reference data to provide more realistic values for the biomechanical variables across multiple anatomical levels. Moreover, the tendon models that are typically used in musculoskeletal modeling are too stiff. SIGNIFICANCE: Calibrated musculoskeletal models informed by experimental measurements give access to an augmented range of biomechanical variables that might not be easily measured with sensors alone.

Strain inhibition of bacterial collagenase is consistent with a collagen fibril uncrimping mechanism in rat tail tendons.

Mechanical strain inhibits bacterial collagenase from cleaving collagen. Additionally, the toe region of a soft tissue's force-elongation curve arises from sequentially engaging collagen fibrils as the tissue lengthens. Together, these phenomena suggest that mechanical strain may gradually inhibit collagenase activity through a soft tissue's toe region. Therefore, this investigation sought to test this hypothesis. 92 rat tail tendon fascicles from 3 female sentinel animals underwent preliminary stiffness tests, and their force-elongation curves were fit to a collagen distribution model. This distribution-based model calculated the force magnitude corresponding to p% of collagen fibril engagement. Specimens were separated into one of five levels of p, and that level of force was maintained for two hours while being exposed to 0.054 U/mL of bacterial collagenase from C. histolyticum. The specimens were strained to failure following the creep test, and the relative reduction in stiffness was quantified to estimate the fraction of digested fibrils. Every 10% additional collagen engagement corresponded to a 6.3% (97% highest density interval: 4.3 - 8.4%) retention of stiffness, which indicated collagenase inhibition. The results of this investigation were consistent with a strain-inhibition hypothesis along with the established uncrimping mechanism in the toe region. These results support an interaction between mechanical strain and collagenolysis, which may be valuable for disease prevention or treatment.

The effects of periodic and noisy tendon vibration on a kinesthetic targeting task.

Tendon vibration is used extensively to assess the role of peripheral mechanoreceptors in motor control, specifically, the muscle spindles. Periodic tendon vibration is known to activate muscle spindles and induce a kinesthetic illusion that the vibrated muscle is longer than it actually is. Noisy tendon vibration has been used to assess the frequency characteristics of proprioceptive reflex pathways during standing; however, it is unknown if it induces the same kinesthetic illusions as periodic vibration. The purpose of the current study was to assess the effects of both periodic and noisy tendon vibration in a kinesthetic targeting task. Participants (N = 15) made wrist extension movements to a series of visual targets without vision of the limb, while their wrist flexors were either vibrated with periodic vibration (20, 40, 60, 80, and 100 Hz), or with noisy vibration which consisted of filtered white noise with power between ~ 20 and 100 Hz. Overall, our results indicate that both periodic and noisy vibration can induce robust targeting errors during a wrist targeting task. Specifically, the vibration resulted in an undershooting error when moving to the target. The findings from this study have important implications for the use of noisy tendon vibration to assess proprioceptive reflex pathways and should be considered when designing future studies using noisy vibration.