Surrogate modeling of articular cartilage degradation to understand the synergistic role of MMP-1 and MMP-9: a case study

Biomechanics and Modeling in Mechanobiology - A characteristic feature of arthritic diseases is cartilage extracellular matrix (ECM) degradation, often orchestrated by the overexpression of matrix...     

Effect of collagenase–gelatinase ratio on the mechanical properties of a collagen fibril: a combined Monte Carlo–molecular dynamics study

Loading in cartilage is supported primarily by fibrillar collagen, and damage will impair the function of the tissue, leading to pathologies such as osteoarthritis. Damage is initiated by two types of matrix metalloproteinases, collagenase and gelatinase, that cleave and denature the collagen fibrils in the tissue. Experimental and modeling studies have revealed insights into the individual contributions of these two types of MMPs, as well as the mechanical response of intact fibrils and fibrils that have experienced random surface degradation. However, no research has comprehensively examined the combined influences of collagenases and gelatinases on collagen degradation nor studied the mechanical consequences of biological degradation of collagen fibrils. Such preclinical examinations are required to gain insights into understanding, treating, and preventing degradation-related cartilage pathology. To develop these insights, we use sequential Monte Carlo and molecular dynamics simulations to probe the effect of enzymatic degradation on the structure and mechanics of a single collagen fibril. We find that the mechanical response depends on the ratio of collagenase to gelatinase—not just the amount of lost fibril mass—and we provide a possible mechanism underlying this phenomenon. Overall, by characterizing the combined influences of collagenases and gelatinases on fibril degradation and mechanics at the preclinical research stage, we gain insights that may facilitate the development of targeted interventions to prevent the damage and loss of mechanical integrity that can lead to cartilage pathology.

     

In vivo measurement of dynamic rectus femoris function at postures representative of early swing phase

Forward dynamic models suggest that muscle-induced joint motions depend on dynamic coupling between body segments. As a result, biarticular muscles may exhibit non-intuitive behavior in which the induced joint motion is opposite to that assumed based on anatomy. Empirical validation of such predictions is important for models to be relied upon to characterize muscle function. In this study, we measured, in vivo, the hip and knee accelerations induced by electrical stimulation of the rectus femoris (RF) and the vastus medialis (VM) at postures representatives of the toe-off and early swing phases of the gait cycle. Seven healthy young subjects were positioned side-lying with their lower limb supported on air bearings while a 90 ms pulse train stimulated each muscle separately or simultaneously. Lower limb kinematics were measured and compared to predictions from a similarly configured dynamic model of the lower limb. We found that both RF and VM, when stimulated independently, accelerated the hip and knee into extension at these postures, consistent with model predictions. Predicted ratios of hip acceleration to knee acceleration were generally within 1 s.d. of average values. In addition, measured responses to simultaneous RF and VM stimulation were within 13% of predictions based on the assumption that joint accelerations induced by activating two muscles simultaneously can be found by adding the joint accelerations induced by activating the same muscles independently. These results provide empirical evidence of the importance of considering dynamic effects when interpreting the role of muscles in generating movement.     

Biomechanical impairments and gait adaptations post-stroke: Multi-factorial associations

Understanding the potential causes of both reduced gait speed and compensatory frontal plane kinematics during walking in individuals post-stroke may be useful in developing effective rehabilitation strategies. Multiple linear regression analysis was used to select the combination of paretic limb impairments (frontal and sagittal plane hip strength, sagittal plane knee and ankle strength, and multi-joint knee/hip torque coupling) which best estimate gait speed and compensatory pelvic obliquity velocities at toeoff. Compensatory behaviors were defined as deviations from control subjects’ values. The gait speed model (n=18; p=0.003) revealed that greater hip abduction strength and multi-joint coupling of sagittal plane knee and frontal plane hip torques were associated with decreased velocity; however, gait speed was positively associated with paretic hip extension strength. Multi-joint coupling was the most influential predictor of gait speed. The second model (n=15; p<0.001) revealed that multi-joint coupling was associated with increased compensatory pelvic movement at toeoff; while hip extension and flexion and knee flexion strength were associated with reduced frontal plane pelvic compensations. In this case, hip extension strength had the greatest influence on pelvic behavior. The analyses revealed that different yet overlapping sets of single joint strength and multi-joint coupling measures were associated with gait speed and compensatory pelvic behavior during walking post-stroke. These findings provide insight regarding the potential impact of targeted rehabilitation paradigms on improving speed and compensatory kinematics following stroke.     

A multiscale synthesis: characterizing acute cartilage failure under an aggregate tibiofemoral joint loading

Biomechanics and Modeling in Mechanobiology - Knee articular cartilage is characterized by a complex mechanical behavior, posing a challenge to develop an efficient and precise model. We argue that...     

The effect of vastus medialis forces on patello-femoral contact: a model-based study

A mathematical model of the patello-femoral joint was introduced to investigate the impact of the vastus medialis (longus, obliquus) forces on the lateral contact force levels. In the model, the quadriceps were represented as five separate forces: vastus lateralis, vastus intermedius, rectus femoris, vastus medialis longus (VML), and obliquus (VMO). By varying the relative force generation ratios of the quadriceps heads, the patello-femoral contact forces were estimated. We sought to analytically determine the range of forces in the VMO and VML that cause a reduction or an increase of lateral contact forces, often the cause of patello-femoral pain. Our results indicated that increased contact forces are more dependent on combinations of muscle forces than solely VMO weakness. Moreover, our simulation data showed that the contact force levels are also highly dependent on the knee flexion angle. These findings suggest that training targeted to reduce contact forces through certain joint angles could actually result in a significant increase of the contact forces through other joint angles.     

A Pilot Study on the Feasibility of Robot-Aided Leg Motor Training to Facilitate Active Participation

Robot-aided gait therapy offers a promising approach towards improving gait function in individuals with neurological disorders such as stroke or spinal cord injury. However, incorporation of appropriate control strategies is essential for actively engaging the patient in the therapeutic process. Although several control algorithms (such as assist-as-needed and error augmentation) have been proposed to improve active patient participation, we hypothesize that the therapeutic benefits of these control algorithms can be greatly enhanced if combined with a motor learning task to facilitate neural reorganization and motor recovery. Here, we describe an active robotic training approach (patient-cooperative robotic gait training combined with a motor learning task) using the Lokomat and pilot-tested whether this approach can enhance active patient participation during training. Six neurologically intact adults and three chronic stroke survivors participated in this pilot feasibility study. Participants walked in a Lokomat while simultaneously performing a foot target-tracking task that necessitated greater hip and knee flexion during the swing phase of the gait. We computed the changes in tracking error as a measure of motor performance and changes in muscle activation as a measure of active subject participation. Repeated practice of the motor-learning task resulted in significant reductions in target-tracking error in all subjects. Muscle activation was also significantly higher during active robotic training compared to simply walking in the robot. The data from stroke participants also showed a trend similar to neurologically intact participants. These findings provide a proof-of-concept demonstration that combining robotic gait training with a motor learning task enhances active participation.     

Cross-validation of a portable,six-degree-of-freedom load cell for use in lower-limb prosthetics research

The iPecs™ load cell is a lightweight, six-degree-of-freedom force transducer designed to fit easily into an endoskeletal prosthesis via a universal mounting interface. Unlike earlier tethered systems, it is capable of wireless data transmission and on-board memory storage, which facilitate its use in both clinical and real-world settings. To date, however, the validity of the iPecs™ load cell has not been rigorously established, particularly for loading conditions that represent typical prosthesis use. The aim of this study was to assess the accuracy of an iPecs™ load cell during in situ human subject testing by cross-validating its force and moment measurements with those of a typical gait analysis laboratory. Specifically, the gait mechanics of a single person with transtibial amputation were simultaneously measured using an iPecs™ load cell, multiple floor-mounted force platforms, and a three-dimensional motion capture system. Overall, the forces and moments measured by the iPecs™ were highly correlated with those measured by the gait analysis laboratory (r>0.86) and RMSEs were less than 3.4% and 5.2% full scale output across all force and moment channels, respectively. Despite this favorable comparison, however, the results of a sensitivity analysis suggest that care should be taken to accurately identify the axes and instrumentation center of the load cell in situations where iPecs™ data will be interpreted in a coordinate system other than its own (e.g., inverse dynamics analysis).     

A model of anterior cruciate ligament reconstructive surgery: A validation construct and computational insights

This study sought to develop a computational framework that emulates the anterior cruciate ligament reconstruction surgery using transtibial portal technique. The proposed model included the tibia–femoral and patella–femoral joints, articular cartilage and menisci. Key surgical parameters were incorporated including bone-patellar-tendon-bone graft excision and pre-tensioning, tunnel morphology, bone plugs, and bone plug fixation. Several simulation steps were parameterized to reflect the clinically reported surgical procedure. Our focus was to explore the intra-operative effects of variations in tunnel directions on the selected metrics of joint mechanics during Lachman and Anterior Drawer tests. A mathematical construct capable of transforming the limited and heterogeneous experimental and surgical data to evidence-based validation was adopted to ensure the viability of the finite element models. We found that the proposed models, subject to a variation in tunnel directions, resulted in simulation outputs that favor the reported experimental data of Lachman and Anterior Drawer tests under uncertainty. Simulation results for a population of three-dimensional tunnel orientations provided insights into the graft–tunnel contact mechanics and the spatial stress distribution in the graft, insights that have been anecdotally observed in prior experimental studies. The intraarticular graft tension was found to be higher than the estimated in tunnel graft force, and larger differences were found for the least inclined tunnels exhibiting higher contact pressures, transverse bending and twisting of the graft and Von-Mises stress at the graft–femoral tunnel interface. Conversely, tunnels with high inclination angles exhibited higher intraarticular graft tension and Von-Mises stress at the graft–tibial bone plug interface.     

The effect of fibrillar degradation on the mechanics of articular cartilage: a computational model

Biomechanics and Modeling in Mechanobiology - The pathogenesis and pathophysiological underpinnings of cartilage degradation are not well understood. Either mechanically or enzymatically mediated...