Sensitivity of knee cartilage biomechanics in finite element analysis to selected Musculoskeletal models.

Knee joint kinematics and kinetics analyzed by musculoskeletal (MS) modeling are often utilized in finite element (FE) models, estimating tissue-level mechanical responses. We compared knee cartilage stresses, strains, and centers of pressure of FE models driven by two widely used MS models, implemented in AnyBody and OpenSim. Minor discrepancies in the results were observed between the models. AnyBody-driven FE models showed slightly higher stresses in the medial tibial cartilage, while OpenSim-driven FE models estimated more anterior and lateral center of pressure. Recognizing these differences in the MS-FE models is important to ensure reliable analysis of cartilage mechanics and failure and simulation of rehabilitation.

Sensitivity analysis of paediatric knee kinematics to the graft surgical parameters during anterior cruciate ligament reconstruction: A sequentially linked neuromusculoskeletal-finite element analysis.

BACKGROUND AND OBJECTIVE: Incidence of paediatric anterior cruciate ligament (ACL) rupture has increased substantially over recent decades. Following ACL rupture, ACL reconstruction (ACLR) surgery is typically performed to restore passive knee stability. This surgery involves replacing the failed ACL with a graft, however, surgeons must select from range of surgical parameters (e.g., type, size, insertion, and pre-tension) with no robust evidence guiding these decisions. This study presents a systemmatic computational approach to study effects of surgical parameter variation on kinematics of paediatric knees. METHODS: This study used sequentially-linked neuromusculoskeletal (NMSK) finite element (FE) models of three paediatric knees to estimate the: (i) sensitivity of post-operative knee kinematics to four surgical parameters (type, size, insertion, and pre-tension) through multi-input multi-output sensitivity analysis; (ii) influence of motion and loading conditions throughout stance phase of walking gait on sensitivity indices; and (iii) influence of subject-specific anatomy (i.e., knee size) on sensitivivty indices. A previously validated FE model of the intact knee for each subject served as a reference against which ACLR knee kinematics were compared. RESULTS: Sensitivity analyses revealed significant influences of surgical parameters on ACLR knee kinematics, albeit without discernible trend favouring any one parameter. Graft size and pre-tension were primary drivers of variation in knee translations and rotations, however, their effects fluctuated across stance indicating motion and loading conditions affect system sensitivity to surgical parameters. Importantly, the sensitivity of knee kinematics to surgical parameter varied across subjects, indicating geometry (i.e., knee size) influenced system sensitivity. Notably, alterations in graft parameters yielded substantial effects on kinematics (normalized root-mean-square-error > 10 %) compared to intact knee models, indicating surgical parameters vary post-operative knee kinematics. CONCLUSIONS: Overall, this initial study highlights the importance of surgical parameter selection on post-operative kinematics in the paediatric ACLR knee, and provides evidence of the need for personalized surgical planning to ultimately enhance patient outcomes.

Tetraspanin profiles of serum extracellular vesicles reflect functional limitations and pain perception in knee osteoarthritis.

BACKGROUND: Emerging evidence suggests that extracellular vesicles (EVs) can play roles in inflammatory processes and joint degradation in primary osteoarthritis (OA), a common age-associated joint disease. EV subpopulations express tetraspanins and platelet markers that may reflect OA pathogenesis. The present study investigated the associations between these EV surface markers and articular cartilage degradation, subjectively and objectively assessed pain, and functional limitations in primary knee OA (KOA). METHODS: Serum EVs were determined by high-sensitivity flow cytometry (large CD61+ EVs) and single particle interferometric reflectance imaging sensor (small CD41+, CD63+, CD81+, and CD9+ EVs) from end-stage KOA patients and controls (n = 8 per group). Knee pain and physical functions were assessed with several health- and pain-related questionnaires, established measurements of physical medicine, and neuromuscular examination. The obtained data were analyzed using supervised and unsupervised univariate and multivariate models. RESULTS: With the combined dataset of cartilage thickness, knee function, pain, sensation, and EV molecular signatures, we identified highly correlated groups of variables and found several EV markers that were statistically significant predictors of pain, physical limitations, and other aspects of well-being for KOA patients, for instance CD41+/CD63+/CD9+ small EVs associated with the range of motion of the knee, physical performance, and pain sensitivity. CONCLUSIONS: Particular serum EV subpopulations showed clear associations with KOA pain and functional limitations, suggesting that their implications in OA pathophysiology warrant further study.

Effects of gait modifications on tissue-level knee mechanics in individuals with medial tibiofemoral osteoarthritis: A proof-of-concept study towards personalized interventions.

Gait modification is a common nonsurgical approach to alter the mediolateral distribution of knee contact forces, intending to decelerate or postpone the progression of mechanically induced knee osteoarthritis (KOA). Nevertheless, the success rate of these approaches is controversial, with no studies conducted to assess alterations in tissue-level knee mechanics governing cartilage degradation response in KOA patients undertaking gait modifications. Thus, here we investigated the effect of different conventional gait conditions and modifications on tissue-level knee mechanics previously suggested as indicators of collagen network damage, cell death, and loss of proteoglycans in knee cartilage. Five participants with medial KOA were recruited and musculoskeletal finite element analyses were conducted to estimate subject-specific tissue mechanics of knee cartilages during two gait conditions (i.e., barefoot and shod) and six gait modifications (i.e., 0°, 5°, and 10° lateral wedge insoles, toe-in, toe-out, and wide stance). Based on our results, the optimal gait modification varied across the participants. Overall, toe-in, toe-out, and wide stance showed the greatest reduction in tissue mechanics within medial tibial and femoral cartilages. Gait modifications could effectually alter maximum principal stress (~20 ± 7%) and shear strain (~9 ± 4%) within the medial tibial cartilage. Nevertheless, lateral wedge insoles did not reduce joint- and tissue-level mechanics considerably. Significance: This proof-of-concept study emphasizes the importance of the personalized design of gait modifications to account for biomechanical risk factors associated with cartilage degradation.

Validation and evaluation of subject-specific finite element models of the pediatric knee.

Finite element (FE) models have been widely used to investigate knee joint biomechanics. Most of these models have been developed to study adult knees, neglecting pediatric populations. In this study, an atlas-based approach was employed to develop subject-specific FE models of the knee for eight typically developing pediatric individuals. Initially, validation simulations were performed at four passive tibiofemoral joint (TFJ) flexion angles, and the resulting TFJ and patellofemoral joint (PFJ) kinematics were compared to corresponding patient-matched measurements derived from magnetic resonance imaging (MRI). A neuromusculoskeletal-(NMSK)-FE pipeline was then used to simulate knee biomechanics during stance phase of walking gait for each participant to evaluate model simulation of a common motor task. Validation simulations demonstrated minimal error and strong correlations between FE-predicted and MRI-measured TFJ and PFJ kinematics (ensemble average of root mean square errors < 5 mm for translations and < 4.1° for rotations). The FE-predicted kinematics were strongly correlated with published reports (ensemble average of Pearson's correlation coefficients (ρ) > 0.9 for translations and ρ > 0.8 for rotations), except for TFJ mediolateral translation and abduction/adduction rotation. For walking gait, NMSK-FE model-predicted knee kinematics, contact areas, and contact pressures were consistent with experimental reports from literature. The strong agreement between model predictions and experimental reports underscores the capability of sequentially linked NMSK-FE models to accurately predict pediatric knee kinematics, as well as complex contact pressure distributions across the TFJ articulations. These models hold promise as effective tools for parametric analyses, population-based clinical studies, and enhancing our understanding of various pediatric knee injury mechanisms. They also support intervention design and prediction of surgical outcomes in pediatric populations.

Sensitivity of simulated knee joint mechanics to selected human and bovine fibril-reinforced poroelastic material properties.

Fibril-reinforced poroviscoelastic material models are considered state-of-the-art in modeling articular cartilage biomechanics. Yet, cartilage material parameters are often based on bovine tissue properties in computational knee joint models, although bovine properties are distinctly different from those of humans. Thus, we aimed to investigate how cartilage mechanical responses are affected in the knee joint model during walking when fibril-reinforced poroviscoelastic properties of cartilage are based on human data instead of bovine. We constructed a finite element knee joint model in which tibial and femoral cartilages were modeled as fibril-reinforced poroviscoelastic material using either human or bovine data. Joint loading was based on subject-specific gait data. The resulting mechanical responses of knee cartilage were compared between the knee joint models with human or bovine fibril-reinforced poroviscoelastic cartilage properties. Furthermore, we conducted a sensitivity analysis to determine which fibril-reinforced poroviscoelastic material parameters have the greatest impact on cartilage mechanical responses in the knee joint during walking. In general, bovine cartilage properties yielded greater maximum principal stresses and fluid pressures (both up to 30%) when compared to the human cartilage properties during the loading response in both femoral and tibial cartilage sites. Cartilage mechanical responses were very sensitive to the collagen fibril-related material parameter variations during walking while they were unresponsive to proteoglycan matrix or fluid flow-related material parameter variations. Taken together, human cartilage material properties should be accounted for when the goal is to compare absolute mechanical responses of knee joint cartilage as bovine material parameters lead to substantially different cartilage mechanical responses.

Signatures of disease progression in knee osteoarthritis: insights from an integrated multi-scale modeling approach, a proof of concept.

Introduction: Knee osteoarthritis (KOA) is characterized by articular cartilage degeneration. It has been widely accepted that the mechanical joint environment plays a significant role in the onset and progression of this disease. In silico models have been used to study the interplay between mechanical loading and cartilage degeneration, hereby relying mainly on two key mechanoregulatory factors indicative of collagen degradation and proteoglycans depletion. These factors are the strain in collagen fibril direction (SFD) and maximum shear strain (MSS) respectively. Methods: In this study, a multi-scale in silico modeling approach was used based on a synergy between musculoskeletal and finite element modeling to evaluate the SFD and MSS. These strains were evaluated during gait based on subject-specific gait analysis data collected at baseline (before a 2-year follow-up) for a healthy and progressive early-stage KOA subject with similar demographics. Results: The results show that both SFD and MSS factors allowed distinguishing between a healthy subject and a KOA subject, showing progression at 2 years follow-up, at the instance of peak contact force as well as during the stance phase of the gait cycle. At the peak of the stance phase, the SFD were found to be more elevated in the KOA patient with the median being 0.82% higher in the lateral and 0.4% higher in the medial compartment of the tibial cartilage compared to the healthy subject. Similarly, for the MSS, the median strains were found to be 3.6% higher in the lateral and 0.7% higher in the medial tibial compartment of the KOA patient compared to the healthy subject. Based on these intersubject SFD and MSS differences, we were additionally able to identify that the tibial compartment of the KOA subject at risk of progression. Conclusion/discussion: We confirmed the mechanoregulatory factors as potential biomarkers to discriminate patients at risk of disease progression. Future studies should evaluate the sensitivity of the mechanoregulatory factors calculated based on this multi-scale modeling workflow in larger patient and control cohorts.

Multiscale In Silico Modeling of Cartilage Injuries.

Injurious loading of the joint can be accompanied by articular cartilage damage and trigger inflammation. However, it is not well-known which mechanism controls further cartilage degradation, ultimately leading to post-traumatic osteoarthritis. For personalized prognostics, there should also be a method that can predict tissue alterations following joint and cartilage injury. This chapter gives an overview of experimental and computational methods to characterize and predict cartilage degradation following joint injury. Two mechanisms for cartilage degradation are proposed. In (1) biomechanically driven cartilage degradation, it is assumed that excessive levels of strain or stress of the fibrillar or non-fibrillar matrix lead to proteoglycan loss or collagen damage and degradation. In (2) biochemically driven cartilage degradation, it is assumed that diffusion of inflammatory cytokines leads to degradation of the extracellular matrix. When implementing these two mechanisms in a computational in silico modeling workflow, supplemented by in vitro and in vivo experiments, it is shown that biomechanically driven cartilage degradation is concentrated on the damage environment, while inflammation via synovial fluid affects all free cartilage surfaces. It is also proposed how the presented in silico modeling methodology may be used in the future for personalized prognostics and treatment planning of patients with a joint injury.

Alterations in the Functional Knee Alignment Are Not an Effective Strategy to Modify the Mediolateral Distribution of Knee Forces During Closed Kinetic Chain Exercises.

Pain felt while performing rehabilitation exercises could be a reason for the low adherence of knee osteoarthritis patients to physical rehabilitation. Reducing compressive forces on the most affected knee regions may help to mitigate the pain. Knee frontal plane positioning with respect to pelvis and foot (functional knee alignment) has been shown to modify the mediolateral distribution of the tibiofemoral joint contact force in walking. Hence, different functional knee alignments could be potentially used to modify joint loading during rehabilitation exercises. The aim was to understand whether utilizing different alignments is an effective strategy to unload specific knee areas while performing rehabilitation exercises. Eight healthy volunteers performed 5 exercises with neutral, medial, and lateral knee alignment. A musculoskeletal model was modified for improved prediction of tibiofemoral contact forces and used to evaluate knee joint kinematics, moments, and contact forces. Functional knee alignment had only a small and inconsistent effect on the mediolateral distribution joint contact force. Moreover, the magnitude of tibiofemoral and patellofemoral contact forces, knee moments, and measured muscle activities was not significantly affected by the alignment. Our results suggest that altering the functional knee alignment is not an effective strategy to unload specific knee regions in physical rehabilitation.

An EMG-Assisted Muscle-Force Driven Finite Element Analysis Pipeline to Investigate Joint- and Tissue-Level Mechanical Responses in Functional Activities: Towards a Rapid Assessment Toolbox.

Joint tissue mechanics (e.g., stress and strain) are believed to have a major involvement in the onset and progression of musculoskeletal disorders, e.g., knee osteoarthritis (KOA). Accordingly, considerable efforts have been made to develop musculoskeletal finite element (MS-FE) models to estimate highly detailed tissue mechanics that predict cartilage degeneration. However, creating such models is time-consuming and requires advanced expertise. This limits these complex, yet promising, MS-FE models to research applications with few participants and makes the models impractical for clinical assessments. Also, these previously developed MS-FE models have not been used to assess activities other than gait. This study introduces and verifies a semi-automated rapid state-of-the-art MS-FE modeling and simulation toolbox incorporating an electromyography- (EMG) assisted MS model and a muscle-force driven FE model of the knee with fibril-reinforced poro(visco)elastic cartilages and menisci. To showcase the usability of the pipeline, we estimated joint- and tissue-level knee mechanics in 15 KOA individuals performing different daily activities. The pipeline was verified by comparing the estimated muscle activations and joint mechanics to existing experimental data. To determine the importance of the EMG-assisted MS analysis approach, results were compared to those from the same FE models but driven by static-optimization-based MS models. The EMG-assisted MS-FE pipeline bore a closer resemblance to experiments compared to the static-optimization-based MS-FE pipeline. Importantly, the developed pipeline showed great potential as a rapid MS-FE analysis toolbox to investigate multiscale knee mechanics during different activities of individuals with KOA.

Toward Tailored Rehabilitation by Implementation of a Novel Musculoskeletal Finite Element Analysis Pipeline.

Tissue-level mechanics (e.g., stress and strain) are important factors governing tissue remodeling and development of knee osteoarthritis (KOA), and hence, the success of physical rehabilitation. To date, no clinically feasible analysis toolbox has been introduced and used to inform clinical decision making with subject-specific in-depth joint mechanics of different activities. Herein, we utilized a rapid state-of-the-art electromyography-assisted musculoskeletal finite element analysis toolbox with fibril-reinforced poro(visco)elastic cartilages and menisci to investigate knee mechanics in different activities. Tissue mechanical responses, believed to govern collagen damage, cell death, and fixed charge density loss of proteoglycans, were characterized within 15 patients with KOA while various daily activities and rehabilitation exercises were performed. Results showed more inter-participant variation in joint mechanics during rehabilitation exercises compared to daily activities. Accordingly, the devised workflow may be used for designing subject-specific rehabilitation protocols. Further, results showed the potential to tailor rehabilitation exercises, or assess capacity for daily activity modifications, to optimally load knee tissue, especially when mechanically-induced cartilage degeneration and adaptation are of interest.

Effect of osteoporosis-related reduction in the mechanical properties of bone on the acetabular fracture during a sideways fall: A parametric finite element approach.

PURPOSE: The incidence of acetabular fractures due to low-energy falls is increasing among the geriatric population. Studies have shown that several biomechanical factors such as body configuration, impact velocity, and trochanteric soft-tissue thickness contribute to the severity and type of acetabular fracture. The effect of reduction in apparent density and elastic modulus of bone as well as other bone mechanical properties due to osteoporosis on low-energy acetabular fractures has not been investigated. METHODS: The current comprehensive finite element study aimed to study the effect of reduction in bone mechanical properties (trabecular, cortical, and trabecular + cortical) on the risk and type of acetabular fracture. Also, the effect of reduction in the mechanical properties of bone on the load-transferring mechanism within the pelvic girdle was examined. RESULTS: We observed that while the reduction in the mechanical properties of trabecular bone considerably affects the severity and area of trabecular bone failure, reduction in mechanical properties of cortical bone moderately influences both cortical and trabecular bone failure. The results also indicated that by reducing bone mechanical properties, the type of acetabular fracture turns from elementary to associated, which requires a more extensive intervention and rehabilitation period. Finally, we observed that the cortical bone plays a substantial role in load transfer, and by increasing reduction in the mechanical properties of cortical bone, a greater share of load is transmitted toward the pubic symphysis. CONCLUSION: This study increases our understanding of the effect of osteoporosis progression on the incidence of low-energy acetabular fractures. The osteoporosis-related reduction in the mechanical properties of cortical bone appears to affect both the cortical and trabecular bones. Also, during the extreme reduction in the mechanical properties of bone, the acetabular fracture type will be more complicated. Finally, during the final stages of osteoporosis (high reduction in mechanical properties of bone) a smaller share of impact load is transferred by impact-side hemipelvis to the sacrum, therefore, an osteoporotic pelvis might mitigate the risk of sacral fracture.

Determination of the correlation between muscle forces obtained from OpenSim and muscle activities obtained from electromyography in the elderly.

Measurement of muscle forces related to aging can help to better identify the gait impairment mechanisms in the elderly. To this end, musculoskeletal modeling has been developed to estimate muscle forces. This study aimed to check the validity of OpenSim modeling (i.e., computed muscle control) approach in elderly subjects. Kinematic and kinetic data and Electromyography (EMG) signals for four different muscles were collected in nine healthy elderly males during walking. Dynamic simulation was done within OpenSim. Correlation analysis was performed to quantitatively compare the maximum estimated muscle forces with maximum measured muscle activities during the first double limb support, single limb support, and the second double limb support phases. The area-time plots of OpenSim and EMG data during gait cycle were obtained for qualitative assessment. In quantitative assessment, a low to moderate correlation was observed for the peak of muscle force and muscle activation of four muscles during sub phases of gait. The muscle forces pattern from OpenSim was found to be relatively similar to the muscle activity pattern from EMG especially for Gastrocnemius Medialis. A low to moderate consistency between OpenSim and EMG in the elderly can be explained by using a single mathematical estimation approach.

An evaluation of the efficiency of endpoint control on the correction of scoliotic curve with brace. A case study.

PURPOSE: The use of braces is one of the conservative treatment approaches recommended for scoliotic subjects. However, the main question posted here is how to improve the efficiency of braces to control the scoliotic curve or to decrease its progression. The aim of this study was to evaluate the efficiency of various boundary conditions (endpoint control) of brace on the correction of scoliotic curves. METHOD: CT scan images of a scoliotic subject, with double lumbar and thoracic curves, was used to produce 3d model of spine. The correction of spine (decrease in scoliotic curves) was determined following the use of transverse (lateral-to-medial direction) and the combination of transverse and vertical (upward directed force, traction) forces on spine in Abaqus software. The effects of pelvic fixation (pelvic basket of a brace) on both sides (basket enclosed pelvic in both sides), on one side (basket enclosed the pelvic in only one side), and fixation of lumbar (part of the brace encircled the lumbar area) were evaluated in this study. RESULTS: The results of this study showed that the effect of vertical forces (traction) was more than that of transverse force. Moreover, the combination of vertical and transverse forces on lumbar and thoracic curves correction was more than that of other conditions (only transverse forces). The best correction was achieved with lumbar fixation and with combination of vertical and transverse forces. CONCLUSIONS: The use the combination of vertical and transverse forces may be suggested to correct the scoliotic curve. Moreover, the efficiency of lumbar fixation in frontal plane seems to be more than pelvic fixation to correct scoliotic curve. The outputs of this study can be used to design new braces for scoliotic subjects.

An Evaluation of the Effect of Vision on Standing Stability in the Early Stage of Parkinson's Disease.

BACKGROUND: Postural instability is a common disorder in Parkinson's disease (PD). The aim of this study was to evaluate stance stability of the subjects at the early stage of PD with both linear and nonlinear approaches. Moreover, this study aimed to find the effect of visual control on quiet stance postural control in these patients. METHOD: Seventeen PD patients (Hoehn/Yahr scale: 1) and 17 healthy control subjects were instructed to maintain quiet postural stance in 2 conditions (opened eyes and closed eyes). Four linear (excursion, path length, velocity, root mean square) and 1 nonlinear (approximate entropy) center of pressure (COP) parameters were calculated. A 2 × 2 mixed ANOVA was used for the final analysis. RESULTS: Although there was no difference between the stability of PD patients and healthy control subjects based on excursion of COP in both mediolateral (ML) and anteroposterior (AP) directions, other linear parameters (path length of COP sways, velocity of COP sways, and root mean square in both ML and AP planes) showed that PD patients were significantly unstable compared to normal subjects (p value < 0.05). Vision influenced the stability of both groups significantly. The interaction of vision and group was not significant based on linear and nonlinear stability parameters. CONCLUSION: Although patients in the early stage of PD seem to be unstable based on COP linear measures, their postural control system is still flexible to adapt to environmental perturbations in quiet stance and they are not more visually dependent than healthy subjects to control stability in this position.

Sound side joint contact forces in below knee amputee gait with an ESAR prosthetic foot.

The incidence of knee and hip joint osteoarthritis in subjects with below knee amputation (BK) appears significantly higher compared to unimpaired subjects, especially in the intact side. However, it is controversial if constant higher loads on the sound side are one of the major factors for an increased osteoarthritis (OA) incidence in subjects with BK, beside other risk factors, e.g. with respect to metabolism. The aim wasto investigate joint contact forces (JCF) calculated by a musculoskeletal model in the intact side and to compare it with those of unimpaired subjects and to further elucidate in how far increased knee JCF are associated with increased frontal plane knee moments. A group of seven subjects with BK amputation and a group of ten unimpaired subjects were recruited for this study. Gait data were measured by 3D motion capture and force plates. OpenSim software was applied to calculate JCF. Maximum joint angles, ground reaction forces, and moments as well as time distance parameters were determined and compared between groups showing no significant differences, with some JCF components of knee and hip even being slightly smaller in subjects with BK compared to the reference group. This positive finding may be due to the selected ESAR foot. However, other beneficial factors may also have influenced this positive result such as the general good health status of the subjects or the thorough and proper fitting and alignment of the prosthesis.

Performance of spinal cord injury individuals while standing with the Mohammad Taghi Karimi reciprocal gait orthosis (MTK-RGO).

Most patients with spinal cord injury use a wheelchair to transfer from place to place, however they need to stand and walk with orthosis to improve their health status. Although many orthoses have been designed for paraplegic patients, they have experienced various problems while in use. A new type of reciprocal gait orthosis was designed in the Bioengineering Unit of Strathclyde University to solve the problems of the available orthoses. Since there was no research undertaken regarding testing of the new orthosis on paraplegic subjects, this study was aimed to evaluate the new orthosis during standing of paraplegic subjects. Five paraplegic patients with lesion level between T12 and L1 and aged matched normal subjects were recruited into this study. The stability of subjects was evaluated during quiet standing and while undertaking hand tasks during standing with the new orthosis and the knee ankle foot orthosis (KAFO). The difference between the performances of paraplegic subjects while standing with both orthoses, and between the function of normal and paraplegic subjects were compared using the paired t test and independent sample t test, respectively. The stability of paraplegic subjects in standing with the new orthosis was better than that of the KAFO orthosis (p < 0.05). Moreover, the force applied on the crutch differed between the orthoses. The functional performance of paraplegic subjects was better with the new orthosis compared with normal subjects. The performance of paraplegic subjects while standing with the new orthosis was better than the KAFO. Therefore, the new orthosis may be useful to improve standing and walking in patients with paraplegia.