Agent-based model provides insight into the mechanisms behind failed regeneration following volumetric muscle loss injury

Skeletal muscle possesses a remarkable capacity for repair and regeneration following a variety of injuries. When successful, this highly orchestrated regenerative process requires the contribution of several muscle resident cell populations including satellite stem cells (SSCs), fibroblasts, macrophages and vascular cells. However, volumetric muscle loss injuries (VML) involve simultaneous destruction of multiple tissue components (e.g., as a result of battlefield injuries or vehicular accidents) and are so extensive that they exceed the intrinsic capability for scarless wound healing and result in permanent cosmetic and functional deficits. In this scenario, the regenerative process fails and is dominated by an unproductive inflammatory response and accompanying fibrosis. The failure of current regenerative therapeutics to completely restore functional muscle tissue is not surprising considering the incomplete understanding of the cellular mechanisms that drive the regeneration response in the setting of VML injury. To begin to address this profound knowledge gap, we developed an agent-based model to predict the tissue remodeling response following surgical creation of a VML injury. Once the model was able to recapitulate key aspects of the tissue remodeling response in the absence of repair, we validated the model by simulating the tissue remodeling response to VML injury following implantation of either a decellularized extracellular matrix scaffold or a minced muscle graft. The model suggested that the SSC microenvironment and absence of pro-differentiation SSC signals were the most important aspects of failed muscle regeneration in VML injuries. The major implication of this work is that agent-based models may provide a much-needed predictive tool to optimize the design of new therapies, and thereby, accelerate the clinical translation of regenerative therapeutics for VML injuries.     

A phenomenological model and validation of shortening-induced force depression during muscle contractions

History-dependent effects on muscle force development following active changes in length have been measured in a number of experimental studies. However, few muscle models have included these properties or examined their impact on force and power output in dynamic cyclic movements. The goal of this study was to develop and validate a modified Hill-type muscle model that includes shortening-induced force depression and assess its influence on locomotor performance. The magnitude of force depression was defined by empirical relationships based on muscle mechanical work. To validate the model, simulations incorporating force depression were developed to emulate single muscle in situ and whole muscle group leg extension experiments. There was excellent agreement between simulation and experimental values, with in situ force patterns closely matching the experimental data (average RMS error <1.5 N) and force depression in the simulated leg extension exercise being similar in magnitude to experimental values (6.0% vs. 6.5%, respectively). To examine the influence of force depression on locomotor performance, simulations of maximum power pedaling with and without force depression were generated. Force depression decreased maximum crank power by 20–40%, depending on the relationship between force depression and muscle work used. These results indicate that force depression has the potential to substantially influence muscle power output in dynamic cyclic movements. However, to fully understand the impact of this phenomenon on human movement, more research is needed to characterize the relationship between force depression and mechanical work in large muscles with different morphologies.     

Functional analysis of limb recovery following autograft treatment of volumetric muscle loss in the quadriceps femoris

Severe injuries to the extremities often result in muscle trauma and, in some cases, significant volumetric muscle loss (VML). These injuries continue to be challenging to treat, with few available clinical options, a high rate of complications, and often persistent loss of limb function. To facilitate the testing of regenerative strategies for skeletal muscle, we developed a novel quadriceps VML model in the rat, specifically addressing functional recovery of the limb. Our outcome measures included muscle contractility measurements to assess muscle function and gait analysis for evaluation of overall limb function. We also investigated treatment with muscle autografts, whole or minced, to promote regeneration of the defect area. Our defect model resulted in a loss of muscle function, with injured legs generating less than 55% of muscle strength from the contralateral uninjured control legs, even at 4 weeks post-injury. The autograft treatments did not result in significant recovery of muscle function. Measures of static and dynamic gait were significantly decreased in the untreated, empty defect group, indicating a decrease in limb function. Histological sections of the affected muscles showed extensive fibrosis, suggesting that this scarring of the muscle may be in part the cause of the loss of muscle function in this VML model. Taken together, these data are consistent with clinical findings of reduced muscle function in large VML injuries. This new model with quantitative functional outcome measures offers a platform on which to evaluate treatment strategies designed to regenerate muscle tissue volume and restore limb function.     

Muscle force estimation in clinical gait analysis using AnyBody and OpenSim

A variety of musculoskeletal models are applied in different modelling environments for estimating muscle forces during gait. Influence of different modelling assumptions and approaches on model outputs are still not fully understood, while direct comparisons of standard approaches have been rarely undertaken. This study seeks to compare joint kinematics, joint kinetics and estimated muscle forces of two standard approaches offered in two different modelling environments (AnyBody, OpenSim). It is hypothesised that distinctive differences exist for individual muscles, while summing up synergists show general agreement. Experimental data of 10 healthy participants (28 ± 5 years, 1.72 ± 0.08 m, 69 ± 12 kg) was used for a standard static optimisation muscle force estimation routine in AnyBody and OpenSim while using two gait-specific musculoskeletal models. Statistical parameter mapping paired t-test was used to compare joint angle, moment and muscle force waveforms in Matlab. Results showed differences especially in sagittal ankle and hip angles as well as sagittal knee moments. Differences were also found for some of the muscles, especially of the triceps surae group and the biceps femoris short head, which occur as a result of different anthropometric and anatomical definitions (mass and inertia of segments, muscle properties) and scaling procedures (static vs. dynamic). Understanding these differences and their cause is crucial to operate such modelling environments in a clinical setting. Future research should focus on alternatives to classical generic musculoskeletal models (e.g. implementation of functional calibration tasks), while using experimental data reflecting normal and pathological gait to gain a better understanding of variations and divergent behaviour between approaches.     

Skeletal muscle reinnervation by reduced axonal numbers results in whole muscle force deficits

Patients sustaining a peripheral nerve injury will frequently experience residual muscle weakness after muscle reinnervation, even if the nerve repair is performed under optimal circumstances to allow rapid muscle reinnervation. The mechanisms responsible for this contractile dysfunction remain unclear. It is hypothesized that after peripheral nerve injury and repair, a reduced number of axons are available for skeletal muscle reinnervation that results in whole muscle force and specific force deficits. A rat model of peroneal nerve injury and repair was designed so that the number of axons available for reinnervation could be systematically reduced. In adult rats, the peroneal nerve to the extensor digitorum longus muscle was either left intact (sham group, n = 8) or divided and repaired with either 50 percent (R50 group, n = 7) or 100 percent (R100 group, n = 8) of the axons in the proximal stump included in the repair. Four months after surgery, maximal tetanic isometric force was measured and specific force was calculated for each animal. Mean tetanic isometric force for extensor digitorum longus muscles from R50 rats (2765.7 +/- 767.6 mN) was significantly lower than sham (4082.8 +/- 196.5 mN) and R100 (3729.0 +/-370.2 mN) rats (p < 0.003). Mean specific force calculations revealed significant deficits in both the R100 (242.1 +/- 30 kN/m2) and R50 (190.6 +/- 51.8 kN/m2) rats compared with the sham animals (295.9 +/- 14 kN/m2) (p < 0.0005). These data support our hypothesis that after peripheral nerve injury and repair, reinnervation of skeletal muscle by a reduced number of axons results in a reduction in tetanic isometric force and specific force. The greater relative reduction in specific force compared with absolute force production after partial nerve repair may indicate that a population of residual denervated muscle fibers is responsible for this deficit.     

Poloxamer 188 reduces the contraction-induced force decline in lumbrical muscles from mdx mice

Duchenne Muscular Dystrophy is a genetic disease caused by the lack of the protein dystrophin. Dystrophic muscles are highly susceptible to contraction-induced injury, and following contractile activity, have disrupted plasma membranes that allow leakage of calcium ions into muscle fibers. Because of the direct relationship between increased intracellular calcium concentration and muscle dysfunction, therapeutic outcomes may be achieved through the identification and restriction of calcium influx pathways. Our purpose was to determine the contribution of sarcolemmal lesions to the force deficits caused by contraction-induced injury in dystrophic skeletal muscles. Using isolated lumbrical muscles from dystrophic (mdx) mice, we demonstrate for the first time that poloxamer 188 (P188), a membrane-sealing poloxamer, is effective in reducing the force deficit in a whole mdx skeletal muscle. A reduction in force deficit was also observed in mdx muscles that were exposed to a calcium-free environment. These results, coupled with previous observations of calcium entry into mdx muscle fibers during a similar contraction protocol, support the interpretation that extracellular calcium enters through sarcolemmal lesions and contributes to the force deficit observed in mdx muscles. The results provide a basis for potential therapeutic strategies directed at membrane stabilization of dystrophin-deficient skeletal muscle fibers.     

The Pleckstrin homology like domain family member,TDAG51, is temporally regulated during skeletal muscle regeneration

The capacity for skeletal muscle to repair from daily insults as well as larger injuries is a vital component to maintaining muscle health over our lifetime. Given the importance of skeletal muscle for our physical and metabolic well-being, identifying novel factors mediating the growth and repair of skeletal muscle will thus build our foundational knowledge and help lead to potential therapeutic avenues for muscle wasting disorders. To that end, we investigated the expression of T-cell death associated gene 51 (TDAG51) during skeletal muscle repair and studied the response of TDAG51 deficient (TDAG51^-/-) mice to chemically-induced muscle damage.TDAG51 mRNA and protein expression within uninjured skeletal muscle is almost undetectable but, in response to chemically-induced muscle damage, protein levels increase by 5 days post-injury and remain elevated for up to 10 days of regeneration. To determine the impact of TDAG51 deletion on skeletal muscle form and function, we compared adult male TDAG51^-/- mice with age-matched wild-type (WT) mice. Body and muscle mass were not different between the two groups, however, in situ muscle testing demonstrated a significant reduction in force production both before and after fatiguing contractions in TDAG51^-/- mice.During the early phases of the regenerative process (5 days post-injury), TDAG51^-/- muscles display a significantly larger area of degenerating muscle tissue concomitant with significantly less regenerating area compared to WT (as demonstrated by embryonic myosin heavy chain expression). Despite these early deficits in regeneration, TDAG51^-/- muscles displayed no morphological deficits by 10 days post injury compared to WT mice.Taken together, the data presented herein demonstrate TDAG51 expression to be upregulated in damaged skeletal muscle and its absence attenuates the early phases of muscle regeneration.     

The importance of neuromuscular rate of force development for physical function in aging and common neurodegenerative disorders – a systematic review

We systematically reviewed existing literature regarding lower extremity neuromuscular rate of force development (RFD), maximal muscle strength (Fmax), and physical function in neurodegenerative populations, and to what extent these outcomes are affected and/or associated. Following PRISMA guidelines, 4 databases (Pubmed, Embase, SPORTDiscus, Web of Science) were searched. Across aging, Parkinson Disease (PD), Alzheimer’s Disease (AD), Multiple Sclerosis (MS), or Stroke, included studies should report (Part 1) deficits in lower extremity RFD, Fmax, and physical function (~ individuals having inferior vs. superior physical function), and/or (Part 2) associations between RFD (or Fmax) and physical function. A total of N=32 studies (n=1087 participants) were included. Part 1: deficits in RFD (-31%, mean; N=22) were comparable to deficits in physical function (-26%; N=7), yet both deficits exceeded that of Fmax (-21%; N=20). Part 2: associations between RFD and physical function (r²=0.13, mean; N=16) were comparable to associations between Fmax and physical function (r²=0.15; N=12). Lower extremity RFD is (1) particularly sensitive (i.e. adapts earlier and/or more extensively) towards neurodegeneration, and more so than Fmax, and (2) of importance for physical function but apparently not superior to Fmax. RFD could serve as a useful indicator/biomarker of changes in neuromuscular function elicited by neurodegeneration.     

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery

Muscle strains are one of the most common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and physical exam alone, however the clinical presentation can vary greatly depending on the extent of injury, the patient''s pain tolerance, etc. In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Biological markers, such as serum creatine kinase levels, are typically elevated with muscle injury, but their levels do not always correlate with the loss of force production. This is even true of histological findings from animals, which provide a "direct measure" of damage, but do not account for all the loss of function. Some have argued that the most comprehensive measure of the overall health of the muscle in contractile force. Because muscle injury is a random event that occurs under a variety of biomechanical conditions, it is difficult to study. Here, we describe an in vivo animal model to measure torque and to produce a reliable muscle injury. We also describe our model for measurement of force from an isolated muscle in situ. Furthermore, we describe our small animal MRI procedure.Download video file.^{(50M, mov)}     

An examination of possible quadriceps force at the time of anterior cruciate ligament injury during landing: A simulation study

Anterior cruciate ligament (ACL) rupture is a common and traumatic injury. Although, identifying the mechanism of ACL injury has received considerable research attention, there are still many unanswered questions. One proposed mechanism asserts that the ACL is injured due to an aggressive quadriceps muscle contraction. However, recently it has been questioned if the magnitude of quadriceps force needed to tear the ACL is physiologically realistic under the conditions where injury occurs during landing (e.g. near full knee extension and within 50ms after impact). To answer this question, a simple simulation model was developed to examine the upper bounds of quadriceps force that can be developed under these conditions. The model included force-length, and force-velocity properties as well as activation dynamics. Model parameters were chosen to provide a high estimate for possible quadriceps force in a young healthy man. The effects of varying quadriceps pre-activation levels were also examined. When using realistic pre-activation levels, the simulated quadriceps force was less than half of what has been shown to cause ACL injury. Even when using maximum pre-activation, the quadriceps force still did not reach close to the level shown to cause injury. Therefore, we conclude that quadriceps force alone seems to be an unlikely mechanism for ACL injury.     

New parameters describing how knee ligaments carry force in situ predict interspecimen variations in laxity during simulated clinical exams

Knee laxity, defined as the net translation or rotation of the tibia relative to the femur in a given direction in response to an applied load, is highly variable from person to person. High levels of knee laxity as assessed during routine clinical exams are associated with first-time ligament injury and graft reinjury following reconstruction. During laxity exams, ligaments carry force to resist the applied load; however, relationships between intersubject variations in knee laxity and variations in how ligaments carry force as the knee moves through its passive envelope of motion, which we refer to as ligament engagement, are not well established. Thus, the objectives of this study were, first, to define parameters describing ligament engagement and, then, to link variations in ligament engagement and variations in laxity across a group of knees. We used a robotic manipulator in a cadaveric knee model (n = 20) to quantify how important knee stabilizers, namely the anterior and posterior cruciate ligaments (ACL and PCL, respectively), as well as the medial collateral ligament (MCL) engage during respective tests of anterior, posterior, and valgus laxity. Ligament engagement was quantified using three parameters: (1) in situ slack, defined as the relative tibiofemoral motion from the neutral position of the joint to the position where the ligament began to carry force; (2) in situ stiffness, defined as the slope of the linear portion of the ligament force–tibial motion response; and (3) ligament force at the peak applied load. Knee laxity was related to parameters of ligament engagement using univariate and multivariate regression models. Variations in the in situ slack of the ACL and PCL predicted anterior and posterior laxity, while variations in both in situ slack and in situ stiffness of the MCL predicted valgus laxity. Parameters of ligament engagement may be useful to further characterize the in situ biomechanical function of ligaments and ligament grafts.     

Anterior laxity,lateral tibial slope,and in situ ACL force differentiate knees exhibiting distinct patterns of motion during a pivoting event: A human cadaveric study

Knee instability following anterior cruciate ligament (ACL) rupture compromises function and increases risk of injury to the cartilage and menisci. To understand the biomechanical function of the ACL, previous studies have primarily reported the net change in tibial position in response to multiplanar torques, which generate knee instability. In contrast, we retrospectively analyzed a cohort of 13 consecutively tested cadaveric knees and found distinct motion patterns, defined as the motion of the tibia as it translates and rotates from its unloaded, initial position to its loaded, final position. Specifically, ACL-sectioned knees either subluxated anteriorly under valgus torque (VL-subluxating) (5 knees) or under a combination of valgus and internal rotational torques (VL/IR-subluxating) (8 knees), which were applied at 15 and 30° flexion using a robotic manipulator. The purpose of this study was to identify differences between these knees that could be driving the two distinct motion patterns. Therefore, we asked whether parameters of bony geometry and tibiofemoral laxity (known risk factors of non-contact ACL injury) as well as in situ ACL force, when it was intact, differentiate knees in these two groups. VL-subluxating knees exhibited greater sagittal slope of the lateral tibia by 3.6 ± 2.4° (p = 0.003); less change in anterior laxity after ACL-sectioning during a simulated Lachman test by 3.2 ± 3.2 mm (p = 0.006); and, at the peak applied valgus torque (no internal rotation torque), higher posteriorly directed, in situ ACL force by 13.4 ± 11.3 N and 12.0 ± 11.6 N at 15° and 30° of flexion, respectively (both p ≤ 0.03). These results may suggest that subgroups of knees depend more on their ACL to control lateral tibial subluxation in response to uniplanar valgus and multiplanar valgus and internal rotation torques as mediated by anterior laxity and bony morphology.     

Rapid force recovery in contracting skeletal muscle after brief ischemia is dependent on O(2) availability.

We tested the hypothesis that contracting skeletal muscle can rapidly restore force development during reperfusion after brief total ischemia and that this rapid recovery depends on O(2) availability and not an alternate factor related to blood flow. Isolated canine gastrocnemius muscle (n = 5) was stimulated to contract tetanically (isometric contraction elicited by 8 V, 0.2-ms duration, 200-ms trains, at 50-Hz stimulation) every 2 s until steady-state conditions of muscle blood flow (controlled by pump perfusion) and developed force were attained (3 min). While maintaining the same stimulation pattern, muscle blood flow was then reduced to zero (complete ischemia) for 2 min. Normal blood flow was then restored to the contracting muscle; however, two distinct conditions of oxygenation (at the same blood flow) were sequentially imposed: deoxygenated blood (30 s), blood with normal arterial O(2) content (30 s), a return to deoxygenated blood (30 s), and finally a return to normal arterial O(2) content (90 s). During the ischemic period, force development fell to 39 +/- 6 (SE)% of normal (from 460 +/- 40 to 170 +/- 20 N/100 g). When muscle blood flow was restored to normal by perfusion with deoxygenated blood, developed force continued to decline to 140 +/- 20 N/100 g. Muscle force rapidly recovered to 310 +/- 30 N/100 g (P < 0.05) during the 30 s in which the contracting muscle was perfused with oxygenated blood and then fell again to 180 +/- 30 N/100 g when perfused with blood with low PO(2). These findings demonstrate that contracting skeletal muscle has the capacity for rapid recovery of force development during reperfusion after a short period of complete ischemia and that this recovery depends on O(2) availability and not an alternate factor related to blood flow restoration.     

Trunk muscle activation and associated lumbar spine joint shear forces under different levels of external forward force applied to the trunk.

High anterior intervertebral shear loads could cause low back injuries and therefore the neuromuscular system may actively counteract these forces. This study investigated whether, under constant moment loading relative to L3L4, an increased externally applied forward force on the trunk results in a shift in muscle activation towards the use of muscles with more backward directed lines of action, thereby reducing the increase in total joint shear force. Twelve participants isometrically resisted forward forces, applied at several locations on the trunk, while moments were held constant relative to L3L4. Surface EMG and lumbar curvature were measured, and an EMG-driven muscle model was used to calculate compression and shear forces at all lumbar intervertebral joints. Larger externally applied forward forces resulted in a flattening of the lumbar lordosis and a slightly more backward directed muscle force. Furthermore, the overall muscle activation increased. At the T12L1 to L3L4 joint, resulting joint shear forces remained small (less than 200N) because the average muscle force pulled backward relative to those joints. However, at the L5S1 joint the average muscle force pulled the trunk forward so that the increase in muscle force with increasing externally applied forward force caused a further rise in shear force (by 102.1N, SD=104.0N), resulting in a joint shear force of 1080.1N (SD=150.4N) at 50Nm moment loading. It is concluded that the response of the neuromuscular system to shear force challenges tends to increase rather than reduce the shear loading at the lumbar joint that is subjected to the highest shear forces.     

Fiber-based modeling of in situ ankle ligaments with consideration of progressive failure

Ligament sprains account for a majority of injuries to the foot and ankle complex among athletic populations. The infeasibility of measuring the in situ response and load paths of individual ligaments has precluded a complete characterization of their mechanical behavior via experiment. In the present study a fiber-based modeling approach of in situ ankle ligaments was developed and validated for determining the heterogeneous force-elongation characteristics and the consequent injury patterns. Nine major ankle ligaments were modeled as bundles of discrete elements, corresponding functionally to the structure of collagen fibers. To incorporate the progressive nature of ligamentous injury, the limit strain at the occurrence of fiber failure was described by a distribution function ranging from 12% to 18% along the width of the insertion site. The model was validated by comparing the structural kinetic and kinematic response obtained experimentally and computationally under well-controlled foot rotations. The simulation results replicated the 6 degree-of-freedom bony motion and ligamentous injuries and, by implication, the in situ deformations of the ligaments. Gross stiffness of the whole ligament derived from the fibers was comparable to existing experimental data. The present modeling approach provides a biomechanically realistic, interpretable and computationally efficient way to characterize the in situ ligament slack, sequential and heterogeneous uncrimping of collagen fascicles and failure propagation as the external load is applied. Applications of this model include functional ankle joint mechanics, injury prevention and countermeasure design for athletes.     

Effects of rumen-protected betaine supplementation on meat quality and the composition of fatty and amino acids in growing lambs

Rumen-protected betaine (RPB) can enhance betaine absorption in the small intestine of ruminants, while betaine can alter fat distribution and has the potential to affect the meat quality of livestock. Hence, we hypothesized that RPB might also affect the meat quality of lambs. Sixty male Hu sheep of similar weight (30.47 ± 2.04 kg) were selected and randomly subjected to five different treatments. The sheep were fed a control diet (control treatment, CTL); 1.1 g/day unprotected-betaine supplemented diet (UPB); or doses of 1.1 g/day (low RPB treatment; L-PB), 2.2 g/day (middle RPB treatment; M-PB) or 3.3 g/day (high RPB treatment; H-PB) RPB-supplemented diet for 70 days. Slaughter performance, meat quality, fatty acid and amino acid content in the longissimus dorsi (LD) muscle, shoulder muscle (SM) and gluteus muscle (GM) were measured. Compared with CTL, betaine (including UPB and RPB) supplementation increased the average daily weight gain (ADG) (P < 0.05) and average daily feed intake (P < 0.01) of lambs. Rumen-protected betaine increased ADG (P < 0.05) compared with UPB. With increasing RPB doses, the eye muscle area of the lambs linearly increased (P < 0.05). Compared with CTL, betaine supplementation decreased water loss (P < 0.05) in SM and increased pH₂₄ in the SM (P < 0.05) and GM (P < 0.05). Compared with UPB, RPB decreased water loss in the GM (P < 0.01), decreased shear force (P < 0.05) in the LD and SM and increased the pH of the meat 24 h after slaughter (pH₂₄). With increasing RPB doses, the shear force and b* value in the LD linearly decreased (P < 0.05), and the pH₂₄ of the meat quadratically increased (P < 0.05). Compared with CTL, betaine supplementation increased the polyunsaturated fatty acid in the GM (P < 0.05). Compared with UPB, RPB supplementation decreased the saturated fatty acid (SFA) content in the LD (P < 0.05) and increased the unsaturated fatty acids (UFA), mono-unsaturated fatty acids and UFA/SFA ratio in the LD (P < 0.05). Compared with CTL, the content of histidine in the LD increased with betaine supplementation. Compared with UPB, RPB supplementation increased the content of total free amino acids and flavor amino acids in the LD of lambs (P < 0.05). With increasing RPB, the isoleucine and phenylalanine contents in the LD linearly increased (P < 0.05). Overall, the data collected indicated that the meat quality of lambs (especially in the LD) improved as a result of betaine supplementation, and RPB showed better effects than those of UPB.     

Sprint training attenuates the deficits of force and dynamic stiffness in rat soleus muscle caused by eccentric contractions

We investigated whether sprint training attenuates the deficits in force and dynamic stiffness caused by eccentric contractions to the soleus muscles of Wistar rats. Two groups of male rats were analyzed: sedentary (C, n=8) and trained (T, n=8). T rats were sprint trained for 10 weeks. Subsequently, the right soleus muscles of rats were freed under anesthesia, leaving the bone insertion and blood supply intact. Eccentric contractions were induced by lengthening muscles during tetanic contractions. Force and dynamic stiffness were tested before and after 20 rounds of eccentric contractions. Tension decline was analyzed using a two-state model (first-order kinetics) in the context of Kramer's theory. Training improved the twitch tension (C, 6.44+/-0.6N/cm(2); T, 10.90+/-0.8N/cm(2)), tetanic force (C, 61.74+/-0.6N/cm(2); T, 85.62+/-0.8N/cm(2)), and increased the dynamic stiffness (C, 41.28+/-1.0N/cm(2); T, 49.56+/-3.2N/cm(2)). Twitch tension after eccentric contractions declined to 73% and 75% in C and T groups, respectively, while tetanic tension decreased to 60% and 36% in C and T groups, respectively. After eccentric contractions, dynamic stiffness decreases were smaller in T rats (from 49.56+/-3.2 to 36.09+/-2.1N/cm(2)) than in C rats (from 41.28+/-1.0 to 20.73+/-1.8N/cm(2)). Sprint training increased the dynamic stiffness and tetanic tension of the soleus muscle and protected against the attenuation induced by eccentric contractions. Finally, the two-state model provided evidence that the number of force-generating cross-bridges increases in trained muscle.     

Effect of muscle model parameter scaling for isometric plantar flexion torque prediction

This paper uses a EMG-driven Hill-type muscle model to estimate individual muscle forces of the triceps surae in isometric plantar flexion contractions. A uniform group of 20 young physical-active adult males was instructed to follow a specific contraction protocol with low (20%MVC) and medium-high (60%MVC) contractions, separated by relaxing intervals. The torque calculated by summing the individual muscle forces multiplied by the respective moment arms was compared to the torque measured by a dynamometer. Musculoskeletal parameters from the literature were used. Then, three different “correction factors” or bias have been applied on some of the muscle model parameters. These factors were based on anthropometric and dynamometric measurements: moment arm scaled by bimalleolar diameter, tendon slack length by leg length and optimal force by the maximum torque. Model torque agreement with dynamometer was recalculated with the parameter scales. It was observed that the relative torque estimation error decreased slightly but significantly when all factors were applied simultaneously (12.92±4.94% without scaling to 10.12±1.73%), which resulted mainly from the correction of the maximal muscle force parameter.     

Elevated gastrocnemius forces compensate for decreased hamstrings forces during the weight-acceptance phase of single-leg jump landing: implications for anterior cruciate ligament injury risk

Approximately 320,000 anterior cruciate ligament (ACL) injuries in the United States each year are non-contact injuries, with many occurring during a single-leg jump landing. To reduce ACL injury risk, one option is to improve muscle strength and/or the activation of muscles crossing the knee under elevated external loading. This study?s purpose was to characterize the relative force production of the muscles supporting the knee during the weight-acceptance (WA) phase of single-leg jump landing and investigate the gastrocnemii forces compared to the hamstrings forces. Amateur male Western Australian Rules Football players completed a single-leg jump landing protocol and six participants were randomly chosen for further modeling and simulation. A three-dimensional, 14-segment, 37 degree-of-freedom, 92 muscle-tendon actuated model was created for each participant in OpenSim. Computed muscle control was used to generate 12 muscle-driven simulations, 2 trials per participant, of the WA phase of single-leg jump landing. A one-way ANOVA and Tukey post-hoc analysis showed both the quadriceps and gastrocnemii muscle force estimates were significantly greater than the hamstrings (p<0.001). Elevated gastrocnemii forces corresponded with increased joint compression and lower ACL forces. The elevated quadriceps and gastrocnemii forces during landing may represent a generalized muscle strategy to increase knee joint stiffness, protecting the knee and ACL from external knee loading and injury risk. These results contribute to our understanding of how muscle?s function during single-leg jump landing and should serve as the foundation for novel muscle-targeted training intervention programs aimed to reduce ACL injuries in sport.     

Robust human body model injury prediction in simulated side impact crashes

This study developed a parametric methodology to robustly predict occupant injuries sustained in real-world crashes using a finite element (FE) human body model (HBM). One hundred and twenty near-side impact motor vehicle crashes were simulated over a range of parameters using a Toyota RAV4 (bullet vehicle), Ford Taurus (struck vehicle) FE models and a validated human body model (HBM) Total HUman Model for Safety (THUMS). Three bullet vehicle crash parameters (speed, location and angle) and two occupant parameters (seat position and age) were varied using a Latin hypercube design of Experiments. Four injury metrics (head injury criterion, half deflection, thoracic trauma index and pelvic force) were used to calculate injury risk. Rib fracture prediction and lung strain metrics were also analysed. As hypothesized, bullet speed had the greatest effect on each injury measure. Injury risk was reduced when bullet location was further from the B-pillar or when the bullet angle was more oblique. Age had strong correlation to rib fractures frequency and lung strain severity. The injuries from a real-world crash were predicted using two different methods by (1) subsampling the injury predictors from the 12 best crush profile matching simulations and (2) using regression models. Both injury prediction methods successfully predicted the case occupant's low risk for pelvic injury, high risk for thoracic injury, rib fractures and high lung strains with tight confidence intervals. This parametric methodology was successfully used to explore crash parameter interactions and to robustly predict real-world injuries.