Task-Specific Versus Impairment-Based Training on Locomotor Performance in Individuals With Chronic Spinal Cord Injury: A Randomized Crossover Study.

Background. Many research studies attempting to improve locomotor function following motor incomplete spinal cord injury (iSCI) focus on providing stepping practice. However, observational studies of physical therapy strategies suggest the amount of stepping practice during clinical rehabilitation is limited; rather, many interventions focus on mitigating impairments underlying walking dysfunction. Objective. The purpose of this blinded-assessor randomized trial was to evaluate the effects of task-specific versus impairment-based interventions on walking outcomes in individuals with iSCI. Methods. Using a crossover design, ambulatory participants with iSCI >1-year duration performed either task-specific (upright stepping) or impairment-based training for up to 20 sessions over ≤6 weeks, with interventions alternated after >4 weeks delay. Both strategies focused on achieving higher cardiovascular intensities, with training specificity manipulated by practicing only stepping practice in variable contexts or practicing tasks targeting impairments underlying locomotor dysfunction (strengthening, balance tasks, and recumbent stepping). Results. Significantly greater increases in fastest overground and treadmill walking speeds were observed following task-specific versus impairment-based training, with moderate associations between differences in amount of practice and outcomes. Gains in balance confidence were also observed following task-specific vs impairment-based training, although incidence of falls was also increased with the former protocol. Limited gains were observed with impairment-based training except for peak power during recumbent stepping tests. Conclusion. The present study reinforces work from other patient populations that the specificity of task practice is a critical determinant of locomotor outcomes and suggest impairment-based exercises may not translate to improvements in functional tasks. Clinical Trial Registration URL. https://clinicaltrials.gov/ ; Unique Identifier: NCT02115685.

Locomotor Kinematics and Kinetics Following High-Intensity Stepping Training in Variable Contexts Poststroke.

Background and Purpose. Previous studies suggest that individuals poststroke can achieve substantial gains in walking function following high-intensity locomotor training (LT). Recent findings also indicate practice of variable stepping tasks targeting locomotor deficits can mitigate selected impairments underlying reduced walking speeds. The goal of this study was to investigate alterations in locomotor biomechanics following 3 different LT paradigms. Methods. This secondary analysis of a randomized trial recruited individuals 18 to 85 years old and >6 months poststroke. We compared changes in spatiotemporal, joint kinematics, and kinetics following up to 30 sessions of high-intensity (>70% heart rate reserve [HRR]) LT of variable tasks targeting paretic limb and balance impairments (high-variable, HV), high-intensity LT focused only on forward walking (high-forward, HF), or low-intensity LT (<40% HRR) of variable tasks (low-variable, LV). Sagittal spatiotemporal and joint kinematics, and concentric joint powers were compared between groups. Regressions and principal component analyses were conducted to evaluate relative contributions or importance of biomechanical changes to between and within groups. Results. Biomechanical data were available on 50 participants who could walk ≥0.1 m/s on a motorized treadmill. Significant differences in spatiotemporal parameters, kinematic consistency, and kinetics were observed between HV and HF versus LV. Resultant principal component analyses were characterized by paretic powers and kinematic consistency following HV, while HF and LV were characterized by nonparetic powers. Conclusion. High-intensity LT results in greater changes in kinematics and kinetics as compared with lower-intensity interventions. The results may suggest greater paretic-limb contributions with high-intensity variable stepping training that targets specific biomechanical deficits. Clinical Trial Registration. https://clinicaltrials.gov/ Unique Identifier: NCT02507466.

Effect of investigator observation on gait parameters in individuals with stroke.

Improvements in gait speed following various training paradigms applied to patients post-stroke does not always lead to changes in walking performance, defined as gains in daily stepping activity. We hypothesized that testing conditions, specifically the presence of an observer, influences patient behaviors and resultant outcomes may overestimate their true walking capacity. This potential Hawthorne effect on spatiotemporal and biomechanical measures of locomotor function in individuals post-stroke has not been assessed previously. Fifteen ambulatory individuals with chronic stroke wore instrumented insoles and performed two separate normal-pace walking assessments, including unobserved conditions during which participants were unattended and unaware of data collection, and observed conditions with an investigator present. Gait analysis was conducted outside of a laboratory setting using instrumented insoles equipped with a 3D accelerometer and pressure sensors which captured the spatiotemporal kinematics, vertical ground reaction forces and foot acceleration. Data were compared using paired comparisons, with subsequent correlation and stepwise regression analyses to explore potential associations between Hawthorne-induced changes in walking strategies, gait speed and locomotor performance (daily stepping). Except for cadence, other measures of spatiotemporal parameters and swing kinematics (acceleration) were not significantly different between observed vs unobserved conditions. However, analyses of ground reaction forces revealed significantly greater paretic limb loading (Δ1st peak = 1.5 ± 1.6 N/kg Δ2nd peak = 1.4 ± 1.8 N/kg; p < 0.01) and increases in weight bearing symmetry (11-24%, p < 0.01) during observed vs unobserved conditions. This potential Hawthorne effect was greater in those with slower walking speeds and shorter stride lengths but was not related to daily stepping. The present findings suggest that biomechanical parameters of walking function may be related to the presence of an observer and highlight the need to separately measure locomotor capacity (gait speed) and performance (daily stepping).

Improved walking function in laboratory does not guarantee increased community walking in stroke survivors: Potential role of gait biomechanics.

Reduced daily stepping in stroke survivors may contribute to decreased functional capacity and increased mortality. We investigated the relationships between clinical and biomechanical walking measures that may contribute to changes in daily stepping activity following physical interventions provided to participants with subacute stroke. Following ≤40 rehabilitation sessions, 39 participants were categorized into three groups: responders/retainers increased daily stepping >500 steps/day post-training (POST) without decreases in stepping at 2-6 month follow-up (F/U); responders/non-retainers increased stepping at POST but declined >500 steps/day at F/U; and, non-responders did not change daily stepping from baseline testing (BSL). Gait kinematics and kinetics were evaluated during graded treadmill assessments at BSL and POST. Clinical measures of gait speed, timed walking distance, balance and balance confidence were measured at BSL, POST and F/U. Between-group comparisons and regression analyses were conducted to predict stepping activity from BSL and POST measurements. Baseline and changes in clinical measures of walking demonstrated selective associations with stepping, although kinematic measures appeared to better discriminate responders. Specific measures suggest greater paretic vs non-paretic kinematic changes in responders with training, although greater non-paretic changes predicted greater gains (i.e., smaller declines) in stepping in retainers at F/U. No kinetic variables were primary predictors of changes in stepping activity at POST or F/U. The combined findings indicate specific biomechanical assessments may help differentiate changes in daily stepping activity post-stroke.

Computational analysis of knee joint stability following total knee arthroplasty.

The overall objective of this study was to introduce knee joint power as a potential measure to investigate knee joint stability following total knee arthroplasty (TKA). Specific aims were to investigate whether weakened knee joint stabilizers cause abnormal kinematics and how it influences the knee joint kinetic (i.e., power) in response to perturbation. Patient-specific musculoskeletal models were simulated with experimental gait data from six TKA patients (baseline models). Muscle strength and ligament force parameter were reduced by up to 30% to simulate weak knee joint stabilizers (weak models). Two different muscle recruitment criteria were tested to examine whether altered muscle recruitment pattern can mask the influence of weakened stabilizers on the knee joint kinematics and kinetics. Level-walking knee joint kinematics and kinetics were calculated though force-dependent kinematic and inverse dynamic analyses. Bode analysis was then recruited to estimate the knee joint power in response to a simulated perturbation. Weak models resulted in larger anterior-posterior (A-P) displacement and internal-external (I-E) rotation compared to baseline (I-E: 18.4 ±â€¯8.5 vs. 11.6 ±â€¯5.7 (deg), A-P: 9.7 ±â€¯5.6 vs. 5.5 ±â€¯4.1 (mm)). Changes in muscle recruitment criterion however altered the results such that A-P and I-E were not notably different from baseline models. In response to the simulated perturbation, weak models versus baseline models generated a delayed power response with unbounded magnitudes. Perturbed power behavior of the knee remained unaltered regardless of the muscle recruitment criteria. In conclusion, impairment at the knee joint stabilizers may or may not lead to excessive joint motions but it notably affects the knee joint power in response to a perturbation. Whether perturbed knee joint power is associated with the patient-reported outcome requires further investigation.

Compensation or Recovery? Altered Kinetics and Neuromuscular Synergies Following High-Intensity Stepping Training Poststroke.

BACKGROUND: High-intensity, variable stepping training can improve walking speed in individuals poststroke, although neuromuscular strategies used to achieve faster speeds are unclear. We evaluated changes in joint kinetics and neuromuscular coordination following such training; movement strategies consistent with intact individuals were considered evidence of recovery and abnormal strategies indicative of compensation. METHODS: A total of 15 individuals with stroke (duration: 23 ± 30 months) received ≤40 sessions of high-intensity stepping in variable contexts (tasks and environments). Lower-extremity kinetics and electromyographic (EMG) activity were collected prior to (BSL) and following (POST) training at peak treadmill speeds and speeds matched to peak BSL (MATCH). Primary measures included positive (concentric) joint and total limb powers, measures of interlimb (paretic/nonparetic powers) and intralimb compensation (hip/ankle or knee/ankle powers), and muscle synergies calculated using nonnegative matrix factorization. RESULTS: Gains in most positive paretic and nonparetic joint powers were observed at higher speeds at POST, with decreased interlimb compensation and limited changes in intralimb compensation. There were very few differences in kinetic measures between BSL to MATCH conditions. However, the number of neuromuscular synergies increased significantly following training at both POST and MATCH conditions, indicating gains from training rather than altered speeds. Despite these results, speed improvements were associated primarily with changes in nonparetic versus paretic powers. CONCLUSION: Gains in locomotor function were accomplished by movement strategies consistent with both recovery and compensation. These and other data indicate that both strategies may be necessary to maximize walking function in patients poststroke.

Kinematic and Neuromuscular Adaptations in Incomplete Spinal Cord Injury after High- versus Low-Intensity Locomotor Training.

Recent data demonstrate improved locomotion with high-intensity locomotor training (LT) in individuals with incomplete spinal cord injury (iSCI), although concerns remain regarding reinforcement of abnormal motor strategies. The present study evaluated the effects of LT intensity on kinematic and neuromuscular coordination in individuals with iSCI. Using a randomized, crossover design, participants with iSCI received up to 20 sessions of high-intensity LT, with attempts to achieve 70-85% of age-predicted maximum heart rate (HRmax), or low-intensity LT (50-65% HRmax), following which the other intervention was performed. Specific measures included spatiotemporal variables, sagittal-plane gait kinematics, and neuromuscular synergies from electromyographic (EMG) recordings. Correlation analyses were conducted to evaluate associations between variables. Significant improvements in sagittal-plane joint excursions and intralimb hip-knee coordination were observed following high- but not low-intensity LT when comparing peak treadmill (TM) speed before and after LT. Neuromuscular complexity (i.e., number of synergies to explain >90% of EMG variance) was also increased following high- but not low-intensity LT. Comparison of speed-matched trials confirmed significant improvements in the knee excursion of the less impaired limb and intralimb hip-knee coordination, as well as improvements in neuromuscular complexity following high-intensity LT. These findings suggest greater neuromuscular complexity may be due to LT and not necessarily differences in speeds. Only selected kinematic changes (i.e., weak hip excursion) was correlated to improvements in treadmill speed. In conclusion, LT intensity can facilitate gains in kinematic variables and neuromuscular synergies in individuals with iSCI.

TKA patients with unsatisfying knee function show changes in neuromotor synergy pattern but not joint biomechanics.

Nearly 20% of patients who have undergone total knee arthroplasty (TKA) report persistent poor knee function. This study explores the idea that, despite similar knee joint biomechanics, the neuro-motor synergies may be different between high-functional and low-functional TKA patients. We hypothesized that (1) high-functional TKA recruit a more complex neuro-motor synergy pattern compared to low-functional TKA and (2) high-functional TKA patients demonstrate more stride-to-stride variability (flexibility) in their synergies. Gait and electromyography (EMG) data were collected during level walking for three groups of participants: (i) high-functional TKA patients (n=13); (ii) low-functional TKA patients (n=13) and (iii) non-operative controls (n=18). Synergies were extracted from EMG data using non-negative matrix factorization. Analysis of variance and Spearman correlation analyses were used to investigate between-group differences in gait and neuro-motor synergies. Results showed that synergy patterns were different among the three groups. Control subjects used 5-6 independent neural commands to execute a gait cycle. High functional TKA patients used 4-5 independent neural commands while low-functional TKA patients relied on only 2-3 independent neural commands to execute a gait cycle. Furthermore, stride-to-stride variability of muscles' response to the neural commands was reduced up to 15% in low-functional TKAs compared to the other two groups.

Prediction of Polyethylene Wear Rates from Gait Biomechanics and Implant Positioning in Total Hip Replacement.

BACKGROUND: Patient-specific gait and surgical variables are known to play an important role in wear of total hip replacements (THR). However a rigorous model, capable of predicting wear rate based on a comprehensive set of subject-specific gait and component-positioning variables, has to our knowledge, not been reported. QUESTIONS/PURPOSE: (1) Are there any differences between patients with high, moderate, and low wear rate in terms of gait and/or positioning variables? (2) Can we design a model to predict the wear rate based on gait and positioning variables? (3) Which group of wear factors (gait or positioning) contributes more to the wear rate? PATIENTS AND METHODS: Data on patients undergoing primary unilateral THR who performed a postoperative gait test were screened for inclusion. We included patients with a 28-mm metal head and a hip cup made of noncrosslinked polyethylene (GUR 415 and 1050) from a single manufacturer (Zimmer, Inc). To calculate wear rates from radiographs, inclusion called for patients with a series of standing radiographs taken more than 1 year after surgery. Further, exclusion criteria were established to obtain reasonably reliable and homogeneous wear readings. Seventy-three (83% of included) patients met all criteria, and the final dataset consisted of 43 males and 30 females, 69 ± 10 years old, with a BMI of 27.3 ± 4.7 kg/m2. Wear rates of these patients were determined based on the relative displacement of the femoral head with regard to the cup using a validated computer-assisted X-ray wear-analysis suite. Three groups with low (< 0.1 mm/year), moderate (0.1 to 0.2 mm/year), and high (> 0.2 mm/year) wear were established. Wear prediction followed a two-step process: (1) linear discriminant analysis to estimate the level of wear (low, moderate, or high), and (2) multiple linear and nonlinear regression modeling to predict the exact wear rate from gait and implant-positioning variables for each level of wear. RESULTS: There were no group differences for positioning and gait suggesting that wear differences are caused by a combination of wear factors rather than single variables. The linear discriminant analysis model correctly predicted the level of wear in 80% of patients with low wear, 87% of subjects with moderate wear, and 73% of subjects with high wear based on a combination of gait and positioning variables. For every wear level, multiple linear and nonlinear regression showed strong associations between gait biomechanics, implant positioning, and wear rate, with the nonlinear model having a higher prediction accuracy. Flexion-extension ROM and hip moments in the sagittal and transverse planes explained 42% to 60% of wear rate while positioning factors, (such as cup medialization and cup inclination angle) explained only 10% to 33%. CONCLUSION: Patient-specific wear rates are associated with patients' gait patterns. Gait pattern has a greater influence on wear than component positioning for traditional metal-on-polyethylene bearings. CLINICAL RELEVANCE: The consideration of individual gait bears potential to further reduce implant wear in THR. In the future, a predictive wear model may identify individual, modifiable wear factors for modern materials.

Can a linear combination of gait principal component vectors identify hip OA stages?

Hip osteoarthritis (OA) has been shown to affect gait patterns of lower extremities. However, until now, no specific identifying gait characteristics for the various disease stages of hip OA have emerged. The present study addresses the following questions: (1) does a vector-based principal component analysis (PCA) discriminate between various disease stages? And, is this analysis more robust than using discrete gait variables? (2) Does the elimination of differences in walking speed affect the discriminatory robustness of a vector-based PCA? De-identified data sets of forty-five unilateral hip OA patients with varying disease stages and twenty-three age-matched, healthy control subjects were obtained from an available repository. PCA was performed on trial matrices consisting of all external joint moments and sagittal joint angles of one full gait cycle. Group differences in sagittal angles, external moments and the linear combination of PC vectors were investigated using spatial parameter mapping (SPM), a statistical vector field test. Several individual gait variables (i.e. joint moments or angles) demonstrated differences between healthy and moderately and/or severely affected subjects. Only the hip adduction moment could discriminate between the healthy and the early-stage OA group. There was no variable that could distinguish between all OA disease stages. In contrast, the linear combination of PC vectors demonstrated significant group differences between all stages of osteoarthritis; furthermore, these group differences stayed significant when matched speeds were input to the model.

From normal to fast walking: Impact of cadence and stride length on lower extremity joint moments.

This study aimed to clarify the influence of various speeding strategies (i.e. adjustments of cadence and stride length) on external joint moments. This study investigated the gait of 52 healthy subjects who performed self-selected normal and fast speed walking trials in a motion analysis laboratory. Subjects were classified into three separate groups based on how they increased their speed from normal to fast walking: (i) subjects who increased their cadence, (ii) subjects who increased their stride length and (iii) subjects who simultaneously increased both stride length and cadence. Joint moments were calculated using inverse dynamics and then compared between normal and fast speed trials within and between three groups using spatial parameter mapping. Individuals who increased cadence, but not stride length, to walk faster did not experience a significant increase in the lower limb joint moments. Conversely, subjects who increased their stride length or both stride length and cadence, experienced a significant increase in all joint moments. Additionally, our findings revealed that increasing the stride length had a higher impact on joint moments in the sagittal plane than those in the frontal plane. However, both sagittal and frontal plane moments were still more responsive to the gait speed change than transverse plane moments. This study suggests that the role of speed in altering the joint moment patterns depends on the individual's speed-regulating strategy, i.e. an increase in cadence or stride length. Since the confounding effect of walking speed is a major consideration in human gait research, future studies may investigate whether stride length is the confounding variable of interest.

How human gait responds to muscle impairment in total knee arthroplasty patients: Muscular compensations and articular perturbations.

Post-surgical muscle weakness is prevalent among patients who undergo total knee arthroplasty (TKA). We conducted a probabilistic multi-body dynamics (MBD) to determine whether and to what extent habitual gait patterns of TKA patients may accommodate strength deficits in lower extremity muscles. We analyzed muscular and articular compensations in response to various muscle impairments, and the minimum muscle strength requirements needed to preserve TKA gait patterns in its habitual status. Muscle weakness was simulated by reducing the strength parameter of muscle models in MBD analysis. Using impaired models, muscle and joint forces were calculated and compared versus those from baseline gait i.e. TKA habitual gait before simulating muscle weakness. Comparisons were conducted using a relatively new statistical approach for the evaluation of gait waveforms, i.e. Spatial Parameter Mapping (SPM). Principal component analysis was then conducted on the MBD results to quantify the sensitivity of every joint force component to individual muscle impairment. The results of this study contain clinically important, although preliminary, suggestions. Our findings suggested that: (1) hip flexor and ankle plantar flexor muscles compensated for hip extensor weakness; (2) hip extensor, hip adductor and ankle plantar flexor muscles compensated for hip flexor weakness; (3) hip and knee flexor muscles responded to hip abductor weakness; (4) knee flexor and hip abductor balanced hip adductor impairment; and (5) knee extensor and knee flexor weakness were compensated by hip extensor and hip flexor muscles. Future clinical studies are required to validate the results of this computational study.

Contribution of geometric design parameters to knee implant performance: Conflicting impact of conformity on kinematics and contact mechanics.

BACKGROUND: Articular geometry of knee implant has a competing impact on kinematics and contact mechanics of total knee arthroplasty (TKA) such that geometry with lower contact pressure will impose more constraints on knee kinematics. The geometric parameters that may cause this competing effect have not been well understood. This study aimed to quantify the underlying relationships between implant geometry as input and its performance metrics as output. METHODS: Parametric dimensions of a fixed-bearing cruciate retaining implant were randomized to generate a number of perturbed implant geometries. Performance metrics (i.e., maximum contact pressure, anterior-posterior range of motion [A-P ROM] and internal-external range of motion [I-E ROM]) of each randomized design were calculated using finite element analysis. The relative contributions of individual geometric variables to the performance metrics were then determined in terms of sensitivity indices (SI). RESULTS: The femoral and tibial distal or posterior radii and femoral frontal radius are the key parameters. In the sagittal plane, distal curvature of the femoral and tibial influenced both contact pressure, i.e., SI=0.57; SI=0.65, and A-P ROM, i.e., SI=0.58; SI=0.6, respectively. However, posterior curvature of the femoral and tibial implants had a smaller impact on the contact pressure, i.e., SI=0.31; SI=0.23 and a higher impact on the I-E ROM, i.e., SI=0.72; SI=0.58. It is noteworthy that in the frontal plane, frontal radius of the femoral implant impacted both contact pressure (SI=0.38) and I-E ROM (SI=0.35). CONCLUSION: Findings of this study highlighted how changes in the conformity of the femoral and tibial can impact the performance metrics.

Posterior stabilized versus cruciate retaining total knee arthroplasty designs: conformity affects the performance reliability of the design over the patient population.

Commercially available fixed bearing knee prostheses are mainly divided into two groups: posterior stabilized (PS) versus cruciate retaining (CR). Despite the widespread comparative studies, the debate continues regarding the superiority of one type over the other. This study used a combined finite element (FE) simulation and principal component analysis (PCA) to evaluate "reliability" and "sensitivity" of two PS designs versus two CR designs over a patient population. Four fixed bearing implants were chosen: PFC (DePuy), PFC Sigma (DePuy), NexGen (Zimmer) and Genesis II (Smith & Nephew). Using PCA, a large probabilistic knee joint motion and loading database was generated based on the available experimental data from literature. The probabilistic knee joint data were applied to each implant in a FE simulation to calculate the potential envelopes of kinematics (i.e. anterior-posterior [AP] displacement and internal-external [IE] rotation) and contact mechanics. The performance envelopes were considered as an indicator of performance reliability. For each implant, PCA was used to highlight how much the implant performance was influenced by changes in each input parameter (sensitivity). Results showed that (1) conformity directly affected the reliability of the knee implant over a patient population such that lesser conformity designs (PS or CR), had higher kinematic variability and were more influenced by AP force and IE torque, (2) contact reliability did not differ noticeably among different designs and (3) CR or PS designs affected the relative rank of critical factors that influenced the reliability of each design. Such investigations enlighten the underlying biomechanics of various implant designs and can be utilized to estimate the potential performance of an implant design over a patient population.

Sensitivity analysis of human lower extremity joint moments due to changes in joint kinematics.

Despite the widespread applications of human gait analysis, causal interactions between joint kinematics and joint moments have not been well documented. Typical gait studies are often limited to pure multi-body dynamics analysis of a few subjects which do not reveal the relative contributions of joint kinematics to joint moments. This study presented a computational approach to evaluate the sensitivity of joint moments due to variations of joint kinematics. A large data set of probabilistic joint kinematics and associated ground reaction forces were generated based on experimental data from literature. Multi-body dynamics analysis was then used to calculate joint moments with respect to the probabilistic gait cycles. Employing the principal component analysis (PCA), the relative contributions of individual joint kinematics to joint moments were computed in terms of sensitivity indices (SI). Results highlighted high sensitivity of (1) hip abduction moment due to changes in pelvis rotation (SI = 0.38) and hip abduction (SI = 0.4), (2) hip flexion moment due to changes in hip flexion (SI = 0.35) and knee flexion (SI = 0.26), (3) hip rotation moment due to changes in pelvis obliquity (SI = 0.28) and hip rotation (SI = 0.4), (4) knee adduction moment due to changes in pelvis rotation (SI = 0.35), hip abduction (SI = 0.32) and knee flexion (SI = 0.34), (5) knee flexion moment due to changes in pelvis rotation (SI = 0.29), hip flexion (SI = 0.28) and knee flexion (SI = 0.31), and (6) knee rotation moment due to changes in hip abduction (SI = 0.32), hip flexion and knee flexion (SI = 0.31). Highlighting the "cause-and-effect" relationships between joint kinematics and the resultant joint moments provides a fundamental understanding of human gait and can lead to design and optimization of current gait rehabilitation treatments.

Prediction of in vivo joint mechanics of an artificial knee implant using rigid multi-body dynamics with elastic contacts.

Lower extremity musculoskeletal computational models play an important role in predicting joint forces and muscle activation simultaneously and are valuable for investigating functional outcomes of the implants. However, current computational musculoskeletal models of total knee replacement rarely consider the bearing surface geometry of the implant. Therefore, these models lack detailed information about the contact loading and joint motion which are important factors for evaluating clinical performances. This study extended a rigid multi-body dynamics simulation of a lower extremity musculoskeletal model to incorporate an artificial knee joint, based upon a novel force-dependent kinematics method, and to characterize the in vivo joint contact mechanics during gait. The developed musculoskeletal total knee replacement model integrated the rigid skeleton multi-body dynamics and the flexible contact mechanics of the tibiofemoral and patellofemoral joints. The predicted contact forces and muscle activations are compared against those in vivo measurements obtained from a single patient with good agreements for the medial contact force (root-mean-square error = 215 N, ρ = 0.96) and lateral contact force (root-mean-square error = 179 N, ρ = 0.75). Moreover, the developed model also predicted the motion of the tibiofemoral joint in all degrees of freedom. This new model provides an important step toward the development of a realistic dynamic musculoskeletal total knee replacement model to predict in vivo knee joint motion and loading simultaneously. This could offer a better opportunity to establish a robust virtual modeling platform for future pre-clinical assessment of knee prosthesis designs, surgical procedures and post-operation rehabilitation.