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Recent advancements in computational modeling offer opportunities to refine total knee arthroplasty (TKA) design and treatment strategies. This study developed patient-specific simulator external boundary conditions (EBCs) using a PID-controlled lower limb finite element (FE) model. Calibration of the external actuation required to achieve measured patient-specific joint loading and motion was completed for nine patients with telemetric implants during gait, stair descent, and deep knee bend. The study also compared two EBC scenarios: activity-specific hip AP motion and pelvic rotation (that was averaged across all patients for an activity) and patient-specific hip AP motion and pelvic rotation. Including patient-specific data significantly improved reproduction of joint-level loading, reducing root mean squared error between the target and achieved loading by 28.7% and highlighting the importance of detailed patient data in replicating joint kinematics and kinetics. The principal component analysis (PCA) of the EBCs for the patient dataset showed that one component represented 77.8% of the overall variation, while the first three components represented 97.8%. Given the significant loading variability within the patient cohort, this group of patient-specific models can be run individually to provide insight into expected TKA mechanics variability, and the PCA can be utilized to further create reasonable EBCs that expand the variability evaluated. [ABSTRACT FROM AUTHOR]

Medial patellofemoral ligament reconstruction (MPFLR) has emerged as the procedure of choice for recurrent patellar dislocation. This addresses soft tissue injury but does not address underlying anatomic factors, including trochlear dysplasia, that are commonly present and increase risk of dislocation. Quantification of the stability offered by other surgical interventions, namely, medializing tibial tubercle osteotomy (mTTO) and trochleoplasty, with and without MPFLR, may provide insight for surgical choices in patients with trochlear dysplasia. We developed subject‐specific finite element models based on magnetic resonance scans from a cohort of 20 patients with trochlear dysplasia and recurrent patellar dislocation. The objectives of this study were (1) to compare patella stability after mTTO and trochleoplasty procedures; (2) to evaluate whether it is necessary to perform an MPFLR in combination with the mTTO or trocheoplasty procedure; and (3) to quantify the robustness of patellar stability to variability in knee kinematics. Trochleoplasty performed better than mTTO at stabilizing the patella between 5° and 30° flexion. For both mTTO and trochleoplasty procedures, it was beneficial to also perform MPFLR—inclusion of MPFLR halved the magnitude of patellar laxity predicted in the simulations. Simulations that did not include any medial patellofemoral ligament restraint were also more sensitive to variation in tibiofemoral internal–external kinematics. Clinical Significance: This study highlights differences in stability provided by medializing tibial tubercle osteotomy and trochleoplasty procedures. It also highlights the importance of medial patellofemoral ligament reconstruction in helping to stabilize the joint, regardless of other procedures that may also be performed, and the sensitivity of patellar stability outcomes to tibiofemoral kinematics. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a probabilistic representation of the hip capsule, which is calibrated to experimental capsular torque-rotation behavior and captures the observed variability for use in population-based studies. A finite element model of the hip capsule was developed with structures composed of a fiber-reinforced membrane, represented by 2D quadrilateral elements embedded with tension-only non-linear spring. An average capsule representation was developed by calibrating ligament properties (linear stiffness, reference strain) so that torque-rotation behavior matched mean cadaveric data. A probabilistic capsule was produced by determining the ligament property variability which represented ±2 SD measured in the experiment. Differences between experimental and model kinematics across all positions had RMS error of 4.7°. Output bounds from the optimized probabilistic capsule representation were consistent with ±2 SD of experimental data; the overall RMS error was 5.1°. This model can be employed in population-based finite element studies of THA to assess mechanics in realistic scenarios considering implant design, as well as surgical and patient factors. [ABSTRACT FROM AUTHOR]

ABSTRACT: Pre‐clinical assessment of stability in total knee replacement is crucial for developing preferred implant performance. Current total knee replacement patients often experience joint instability that the human body addresses with compensatory strategies. Specifically, an increased quadriceps‐hamstrings co‐contraction serves to increase joint stability through an increased compressive force across the tibiofemoral joint. The aim of this study is to introduce a novel method to evaluate total knee replacement by determining the compressive loading required to achieve natural knee stability. Four current total knee replacement geometries in both their cruciate‐retaining and posterior‐stabilized forms are modeled in a finite‐element framework. The finite‐element model is initially validated experimentally using traditional knee laxity testing with a constant compressive load and anterior‐posterior displacement or internal‐external rotation. Model predictions of constraint are in reasonable agreement with experimental results (average root mean square errors: 0.46 Nm, 62.5 N). The finite‐element model is subsequently interfaced with a feedback controller to vary the compressive force that the implant requires in order to match experimental natural knee internal‐external and anterior‐posterior stability at different flexion angles. Results show that the lower constraint total knee replacement designs require on average 66.7% more compressive load than the higher constraint designs to achieve natural knee constraint. As expected, total knee replacement stability and compressive load requirements to replicate natural kinematics vary with inclusion of tibiofemoral ligaments. The current study represents a novel approach to evaluate stability in existing total knee replacement geometries and to design implants that better restore natural knee mechanics. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1901–1909, 2018. [ABSTRACT FROM AUTHOR]

Subject-specific hip capsule models could offer insights into impingement and dislocation risk when coupled with computer-aided surgery, but model calibration is time-consuming using traditional techniques. This study developed a framework for instantaneously generating subject-specific finite element (FE) capsule representations from regression models trained with a probabilistic approach. A validated FE model of the implanted hip capsule was evaluated probabilistically to generate a training dataset relating capsule geometry and material properties to hip laxity. Multivariate regression models were trained using 90% of trials to predict capsule properties based on hip laxity and attachment site information. The regression models were validated using the remaining 10% of the training set by comparing differences in hip laxity between the original trials and the regression-derived capsules. Root mean square errors (RMSEs) in laxity predictions ranged from 1.8° to 2.3°, depending on the type of laxity used in the training set. The RMSE, when predicting the laxity measured from five cadaveric specimens with total hip arthroplasty, was 4.5°. Model generation time was reduced from days to milliseconds. The results demonstrated the potential of regression-based training to instantaneously generate subject-specific FE models and have implications for integrating subject-specific capsule models into surgical planning software. [ABSTRACT FROM AUTHOR]

A new six-degree-of-freedom (6-DOF) joint simulator has recently been developed which facilitates testing of implants under more realistic loading conditions than has been possible previously. However, typical wear testing can be very time-consuming, taking weeks or months to complete. A validated computational model is an ideal complement to these types of long-running tests. In this study, a computational counterpart to the new 6-DOF joint simulator was developed and validated. Total knee replacement components were evaluated in both physical and computational simulations, and joint mechanics were compared between the experiment and the model. Kinematic comparisons were carried out for two total knee replacement designs, under loading conditions representative of three different activities of daily living: deep knee bend, gait, and stepdown. The model accurately reproduced the motions obtained in the physical simulator, and appropriately differentiated between activities and between implant designs. Root-mean-square differences in anterior-posterior translations and internal-external rotations were less than 1.7 mm and 1.4°, respectively, for both implant designs and all three dynamic activities. Contact area, and peak and average contact pressure predicted by the model matched experimental measurements with a root-mean-square accuracy of 20 mm 2 , 9 MPa, and 1 MPa, respectively. The computational model of the 6-DOF joint simulator will be a key tool in efficient evaluation of implant mechanics under loading conditions representative of the in vivo environment. These simulations may be used directly in comparison of devices, or may aid in facilitating optimal usage of the physical simulator through determining which activities and/or loading conditions best address specific clinical or design issues, for example, development of worst-case loading profiles for wear testing. [ABSTRACT FROM AUTHOR]

ABSTRACT Treatment for an initial incidence of patellar dislocation is usually conservative management; however, almost half of patients experience a subsequent, or multiple, dislocation(s). Patients often undergo multiple procedures which fail to treat the underlying anatomic abnormalities. The objective of this study was to evaluate interactions between key predisposing anatomic factors to patellar dislocation and identify combinations of abnormal factors which increase the risk of recurrent lateral dislocation. Four factors associated with lateral patellar dislocation were identified (sulcus angle, Insall-Salvati ratio, tibial tubercle-trochlear groove distance, and femoral anteversion). A finite element model of the patellofemoral joint was developed and parameterized so that a value for each factor could be applied and the model geometry/alignment would be modified accordingly. 100 combinations of the four factors were generated in separate computational simulations and resulting kinematics and forces of the patellofemoral joint were recorded. Sulcus angle was the most impactful factor on constraint. Multiple abnormal factors were generally required to produce the extremes of patellar alignment observed in this analysis. Understanding the underlying anatomic factors, and their effect on joint mechanics, for patients with recurrent lateral patellar dislocation will aid in determining optimal treatment pathways on a patient-specific basis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:444-453, 2016. [ABSTRACT FROM AUTHOR]

ABSTRACT The mechanics of the knee are complex and dependent on the shape of the articular surfaces and their relative alignment. Insight into how anatomy relates to kinematics can establish biomechanical norms, support the diagnosis and treatment of various pathologies (e.g., patellar maltracking) and inform implant design. Prior studies have used correlations to identify anatomical measures related to specific motions. The objective of this study was to describe relationships between knee anatomy and tibiofemoral (TF) and patellofemoral (PF) kinematics using a statistical shape and function modeling approach. A principal component (PC) analysis was performed on a 20-specimen dataset consisting of shape of the bone and cartilage for the femur, tibia and patella derived from imaging and six-degree-of-freedom TF and PF kinematics from cadaveric testing during a simulated squat. The PC modes characterized links between anatomy and kinematics; the first mode captured scaling and shape changes in the condylar radii and their influence on TF anterior-posterior translation, internal-external rotation, and the location of the femoral lowest point. Subsequent modes described relations in patella shape and alta/baja alignment impacting PF kinematics. The complex interactions described with the data-driven statistical approach provide insight into knee mechanics that is useful clinically and in implant design. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1620-1630, 2015. [ABSTRACT FROM AUTHOR]

Accurate prediction of loads acting at the joint in total knee replacement (TKR) patients is key to developing experimental or computational simulations which evaluate implant designs under physiological loading conditions. In vivo joint loads have been measured for a small number of telemetric TKR patients, but in order to assess device performance across the entire patient population, a larger patient cohort is necessary. This study investigates the accuracy of predicting joint loads from joint kinematics. Specifically, the objective of the study was to assess the accuracy of internal-external (I-E) and anterior- posterior (A-P) joint load predictions from I-E and A-P motions under a given compressive load, and to evaluate the repeatability of joint load ratios (I-E torque to compressive force (I-E:C), and A-P force to compressive force (A-P:C)) for a range of compressive loading profiles. A tibiofemoral finite element model was developed and used to simulate deep knee bend, chair-rise and step-up activities for five patients. Root-mean-square (RMS) differences in I-E:C and A-P:C load ratios between telemetric measurements and model predictions were less than 1.10e-3 Nm/N and 0.035 N/N for all activities. I-E:C and A-P:C load ratios were consistently reproduced regardless of the compressive force profile applied (RMS differences less than 0.53e-3 Nm/N and 0.010 N/N, respectively). When error in kinematic measurement was introduced to the model, joint load predictions were forgiving to kinematic measurement error when conformity between femoral and tibial components was low. The prevalence of kinematic data, in conjunction with the analysis presented here, facilitates determining the scope of A-P and I-E joint loading ratios experienced by the TKR population. [ABSTRACT FROM AUTHOR]

For clinically predictive testing and design-phase evaluation of prospective total knee replacement (TKR) implants, devices should ideally be evaluated under physiological loading conditions which incorporate population-level variability. A challenge exists for experimental and computational researchers in determining appropriate loading conditions for wear and kinematic knee simulators which reflect in vivo joint loading conditions. There is a great deal of kinematic data available from fluoroscopy studies. The purpose of this work was to develop computational methods to derive anterior-posterior (A-P) and internal-external (I-E) tibiofemoral (TF) joint loading conditions from in vivo kinematic data. Two computational models were developed, a simple TF model, and a more complex lower limb model. These models were driven through external loads applied to the tibia and femur in the TF model, and applied to the hip, ankle and muscles in the lower limb model. A custom feedback controller was integrated with the finite element environment and used to determine the external loads required to reproduce target kinematics at the TF joint. The computational platform was evaluated using in vivo kinematic data from four fluoroscopy patients, and reproduced in vivo A-P and I-E motions and compressive force with a root-mean-square (RMS) accuracy of less than 1 mm, 0.1°, and 40 N in the TF model and in vivo A-P and I-E motions, TF flexion, and compressive loads with a RMS accuracy of less than 1 mm, 0.1°, 1.4°, and 48 N in the lower limb model. The external loading conditions derived from these models can ultimately be used to establish population variability in loading conditions, for eventual use in computational as well as experimental activity simulations. [ABSTRACT FROM AUTHOR]

Cementless tibial fixation in total knee replacement (TKR) has potential for improved fixation and ease of revision. Achieving primary stability in cementless TKR is critical to the performance of the components. Excessive micromotion may prevent osseointegration at the bone-implant interface. Computational finite element (FE) studies have been used to predict micromotion at the interface, but analysis of an entire activity cycle is computational expensive, prohibiting large numbers of analyses. Surrogate modeling methods can be used to train a numerical model to predict the response of an FE model. These models are computationally efficient and are suitable for high-volume or iterative analyses requiring probabilistic, statistical or optimization methods. The objective of this work was to train a surrogate model capable of predicting micromotion over the entire bone-implant interface. A proximal tibial bone with mapped material properties was virtually implanted with a tibial tray. A FE model, with six-degree-of-freedom loads sampled from telemetric patients during walking, was used to generate training data for the surrogate model. The linear response surrogate model was evaluated for six full gait cycles; the average and peak micromotion across the interface, and the percentage of bone-implant interface surface area experiencing micromotions less than 50 and greater than 150 μm were calculated both as a function of the activity cycle and as the composite peak micromotion throughout the cycle. Differences in root-mean-square (RMS) micromotion between FE and surrogate models were less than 14 mm. FE analysis time for a complete gait cycle was 15 h, compared to 30 s for the surrogate model. Surrogate models have significant potential to rapidly predict micromotion over the entire bone-implant interface, allowing greater range in loading conditions to be explored than is possible through conventional methods. [ABSTRACT FROM AUTHOR]

Validated computational knee simulations are valuable tools for design phase development of knee replacement devices. Recently, a dynamic finite element (FE) model of the Kansas knee simulator was kinematically validated during gait and deep flexion cycles. In order to operate the computational simulator in the same manner as the experiment, a proportional–integral–derivative (PID) controller was interfaced with the FE model to control the quadriceps actuator excursion and produce a target flexion profile regardless of implant geometry or alignment conditions. The controller was also expanded to operate multiple actuators simultaneously in order to producein vivoloading conditions at the joint during dynamic activities. Subsequently, the fidelity of the computational model was improved through additional muscle representation and inclusion of relative hip–ankle anterior–posterior (A–P) motion. The PID-controlled model was able to successfully recreatein vivoloading conditions (flexion angle, compressive joint load, medial–lateral load distribution or varus-valgus torque, internal–external torque, A–P force) for deep knee bend, chair rise, stance-phase gait and step-down activities. [ABSTRACT FROM AUTHOR]

Kneeling is required during daily living for many patients after total knee replacement (TKR), yet many patients have reported that they cannot kneel due to pain, or avoid kneeling due to discomfort, which critically impacts quality of life and perceived success of the TKR procedure. The objective of this study was to evaluate the effect of component design on patellofemoral (PF) mechanics during a kneeling activity. A computational model to predict natural and implanted PF kinematics and bone strains after kneeling was developed and kinematics were validated with experimental cadaveric studies. PF joint kinematics and patellar bone strains were compared for implants with dome, medialized dome, and anatomic components. Due to the less conforming nature of the designs, change in sagittal plane tilt as a result of kneeling at 90° knee flexion was approximately twice as large for the medialized-dome and dome implants as the natural case or anatomic implant, which may result in additional stretching of the quadriceps. All implanted cases resulted in substantial increases in bone strains compared with the natural knee, but increased strains in different regions. The anatomic patella demonstrated increased strains inferiorly, while the dome and medialized dome showed increases centrally. An understanding of the effect of implant design on patellar mechanics during kneeling may ultimately provide guidance to component designs that reduces the likelihood of knee pain and patellar fracture during kneeling. [ABSTRACT FROM AUTHOR]

Abstract: By characterizing anatomical differences in size and shape between subjects, statistical shape models enable population-based evaluations in biomechanics. Statistical models have largely focused on individual bones with application to implant sizing, bone fracture and osteoarthritis; however, in joint mechanics applications, the statistical models must consider the geometry of multiple structures of a joint and their relative position. Accordingly, the objectives of this study were to develop a statistical shape and alignment modeling (SSAM) approach to characterize the intersubject variability in bone morphology and alignment for the structures of the knee, to demonstrate the statistical model's ability to describe variability in a training set and to generate realistic instances for use in finite element evaluation of joint mechanics. The statistical model included representations of the bone and cartilage for the femur, tibia and patella from magnetic resonance images and relative alignment of the structures at a known, loaded position in an experimental knee simulator for a training set of 20 specimens. The statistical model described relationships or modes of variation in shape and relative alignment of the knee structures. By generating new ‘virtual subjects’ with physiologically realistic knee anatomy, the modeling approach can efficiently perform investigations into joint mechanics and implant design which benefit from population-based considerations. [Copyright &y& Elsevier]

Posterior-stabilized (PS) total knee arthroplasty (TKA) components employ a tibial post and femoral cam mechanism to guide anteroposterior knee motion in lieu of the posterior cruciate ligament. Some PS TKA patients report a clicking sensation when the post and cam engage, while severe wear and fracture of the post; we hypothesize that these complications are associated with excessive impact velocity at engagement. We evaluated the effect of implant design on engagement dynamics of the post-cam mechanism and resulting polyethylene stresses during dynamic activity. In vitro simulation of a knee bend activity was performed for four cadaveric specimens implanted with PS TKA components. Post-cam engagement velocity and flexion angle at initial contact were determined. The experimental data were used to validate computational predictions of PS mechanics using the same loading conditions. A lower limb model was subsequently utilized to compare engagement mechanics of eight TKA designs, relating differences between implants to geometric design features. Flexion angle and post-cam velocity at engagement demonstrated considerable ranges among designs (23°-89°, and 0.05-0.22 mm/°, respectively). Post-cam velocity was correlated ( r = 0.89) with tibiofemoral condylar design features. Condylar geometry, in addition to post-cam geometry, played a significant role in minimizing engagement velocity and forces and stresses in the post. This analysis guides selection and design of PS implants that facilitate smooth post-cam engagement and reduce edge loading of the post. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1438-1446, 2013 [ABSTRACT FROM AUTHOR]

Patellar resection thickness during total knee replacement (TKR) has been cited as a contributor to patellar fracture, anterior knee pain and quadriceps efficiency; however, optimal thickness required to minimize clinical complications remains unclear. The objectives of the current study were to determine how patellar resection thickness and bone quality impacts patellar bone strain, kinematics, and quadriceps efficiency. A series of specimen-specific finite element models of the knee joint with distributed patellar bone material properties were developed. Each specimen was virtually implanted with a TKR system. Each specimen was analyzed with patellar bone resected to thicknesses which varied from 9 to 14 mm. Simulations with reduced modulus bone were also performed. Each model perturbation was evaluated during a dynamic squat cycle, and bone strain, quadriceps force and six-degree-of-freedom kinematics were predicted. Highest peak bone strain was predicted in the thinnest patellae, indicating greatest risk of patellar fracture; highest median bone strain was predicted in the thickest patellae. Consistent differences in quadriceps efficiency were predicted; in early flexion the thickest patellae required the least quadriceps force. Greater sagittal plane tilt was observed for the thinnest patellae. Reduced modulus models (50% lower modulus) demonstrated an increase in peak bone strain of up to seven times the original modulus models. Understanding the complex interactions between patellar resection thickness, muscle requirements, kinematics, bone quality, and bone property distribution may aid in developing an understanding of which patients are most at risk from patellar fracture and anterior knee pain and how best to treat individuals to reduce potential complications. [ABSTRACT FROM AUTHOR]

Fluoroscopic evaluation of total knee arthroplasty (TKA) has reported sudden anterior translation of the femur relative to the tibia (paradoxical anterior motion) for some cruciate-retaining designs. This motion may be tied to abrupt changes in the femoral sagittal radius of curvature characteristic of traditional TKA designs, as the geometry transitions from a large load-bearing distal radius to a smaller posterior radius which can accommodate femoral rollback. It was hypothesized that a gradually reducing radius may attenuate sudden changes in anterior-posterior motion that occur in mid-flexion with traditional discrete-radius designs. A combined experimental and computational approach was employed to test this hypothesis. A previously developed finite element (FE) model of the Kansas knee simulator (KKS), virtually implanted with multiple implant designs, was used to predict the amount of paradoxical anterior femoral slide during a simulated deep knee bend. The model predicted kinematics demonstrated that incorporating a gradually reducing radius in mid-flexion reduced the magnitude of paradoxical anterior translation between 21% and 68%, depending on the conformity of the tibial insert. Subsequently, both a dual-radius design and a modified design incorporating gradually reducing radii were tested in vitro in the KKS for verification. The model-predicted and experimentally observed kinematics exhibited good agreement, while the average experimental kinematics demonstrated an 81% reduction in anterior translation with the modified design. The FE model demonstrated sufficient sensitivity to appropriately differentiate kinematic changes due to subtle changes in implant design, and served as a useful pre-clinical design-phase tool to improve implant kinematics. [ABSTRACT FROM AUTHOR]

Substantial variation in total knee replacement (TKR) outcomes exists within the patient population. Some of this variability is due to differences in the design of the implanted components and variation in surgical alignment, while other variability is due to differences in the applied forces and torques due to anatomic and physiological differences within a patient population. We evaluated the relative contributions of implant design, surgical alignment, and patient-specific loading variability to overall tibiofemoral joint mechanics to provide insight into which measures can be influenced through design and surgical decisions, and which are inherently dependent on variation within the patient population and should be considered in the robustness of the implant design and surgical procedure. Design, surgical, and loading parameters were assessed using probabilistic finite element methods during simulated stance-phase gait and squat activities. Patient-specific loading was found to be the primary contributor to joint loading and kinematics during low flexion, particularly under conditions of high external loads (for instance, the gait cycle with high internal-external torque), while design and surgical factors, particularly femoral posterior radius and posterior slope of the tibial insert became increasingly important in TKR performance in deeper flexion. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:2015-2024, 2012 [ABSTRACT FROM AUTHOR]

Abstract: Clinical studies demonstrate substantial variation in kinematic and functional performance within the total knee replacement (TKR) patient population. Some of this variation is due to differences in implant design, surgical technique and component alignment, while some is due to subject-specific differences in joint loading and anatomy that are inherently present within the population. Combined finite element and probabilistic methods were employed to assess the relative contributions of implant design, surgical, and subject-specific factors to overall tibiofemoral (TF) and patellofemoral (PF) joint mechanics, including kinematics, contact mechanics, joint loads, and ligament and quadriceps force during simulated squat, stance-phase gait and stepdown activities. The most influential design, surgical and subject-specific factors were femoral condyle sagittal plane radii, tibial insert superior–inferior (joint line) position and coronal plane alignment, and vertical hip load, respectively. Design factors were the primary contributors to condylar contact mechanics and TF anterior–posterior kinematics; TF ligament forces were dependent on surgical factors; and joint loads and quadriceps force were dependent on subject-specific factors. Understanding which design and surgical factors are most influential to TKR mechanics during activities of daily living, and how robust implant designs and surgical techniques must be in order to adequately accommodate subject-specific variation, will aid in directing design and surgical decisions towards optimal TKR mechanics for the population as a whole. [Copyright &y& Elsevier]

Complications of the patellofemoral (PF) joint remain a common cause for revision of total knee replacements. PF complications, such as patellar maltracking, subluxation, and implant failure, have been linked to femoral and patellar component alignment. In this study, a dynamic finite element model of an implanted PF joint was applied in conjunction with a probabilistic simulation to establish relationships between alignment parameters and PF kinematics, contact mechanics, and internal stresses. Both traditional sensitivity analysis and a coupled probabilistic and principal component analysis approach were applied to characterize relationships between implant alignment and resulting joint mechanics. Critical alignment parameters, and combinations of parameters, affecting PF mechanics were identified for three patellar designs (dome, modified dome, and anatomic). Femoral internal-external (I-E) alignment was identified as a critical alignment factor for all component designs, influencing medial-lateral contact force and anterior-posterior translation. The anatomic design was sensitive to patellar flexion-extension (F-E) alignment, while the dome, as expected, was less influenced by rotational alignment, and more by translational position. The modified dome was sensitive to a combination of superior-inferior, F-E, and I-E alignments. Understanding the relationships and design-specific dependencies between alignment parameters can aid preoperative planning, and help focus instrumentation design on those alignment parameters of primary concern. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1167-1175, 2012 [ABSTRACT FROM AUTHOR]

Abstract: Patellofemoral (PF)-related pathologies, including joint laxity, patellar maltracking, cartilage degradation and anterior knee pain, affect nearly 25% of the population. Researchers have investigated the influence of articular geometry on kinematics and contact mechanics in order to gain insight into the etiology of these conditions. The purpose of the current study was to create a three-dimensional statistical shape model of the PF joint and to characterize relationships between PF shape and function (kinematics and contact mechanics). A statistical shape model of the patellar and femoral articular surfaces and their relative alignment was developed from magnetic resonance images. Using 15 shape parameters, the model characterized 97% of the variation in the training set. The first three shape modes primarily described variation in size, patella alta–baja and depth of the sulcus groove. A previously verified finite element model was used to predict kinematics and contact mechanics for each subject. Combining the shape and joint mechanics data, a statistical shape–function model was developed that established quantitative relations of how changes in the shape of the PF joint influence mechanics. The predictive capability of the shape–function model was evaluated by comparing statistical model and finite element predictions, resulting in kinematic root mean square errors of less than 3° and 2.5mm. The key results of the study are dually in the implementation of a novel approach linking statistical shape and finite element models and the relationships elucidated between PF articular geometry and mechanics. [Copyright &y& Elsevier]

Instances of anterior knee pain and patellar fracture are significant complications following total knee replacement (TKR). Bone strain measured in the patella can provide an indication of patellar fracture risk and may also be related to anterior knee pain. The objective of this study was to develop subject-specific finite element models of the patellofemoral (PF) joint including density-mapped material properties to gain insight into the patellar bone strain distribution in the natural and implanted knee. In eight subjects, the volume of bone experiencing strains >0.5% in the implanted condition was ∼200% larger, on average, than the natural condition. An inverse relationship with a correlation of −0.74 was established between postoperative bone volume and strain in the implanted specimens, suggesting that patellar geometry may be a useful indicator of postoperative strain. Comparing strains between regions (superior, inferior, medial, and lateral), it was found that although highly strained bone was evenly distributed between medial and lateral regions in the natural case, the implanted specimens demonstrated significantly larger volumes of highly strained bone medially as a result of substantially lower modulus bone in the medial compartment. Understanding distributions of PF strain may aid in preoperative identification of those patients at risk for patellar fracture or anterior knee pain, guidance regarding altered component placement for at-risk patients, and design of components considering the implications of PF load transfer and patellar strain distribution. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:232-239, 2011 [ABSTRACT FROM AUTHOR]

Abstract: Many aspects of biomechanics are variable in nature, including patient geometry, joint mechanics, implant alignment and clinical outcomes. Probabilistic methods have been applied in computational models to predict distributions of performance given uncertain or variable parameters. Sensitivity analysis is commonly used in conjunction with probabilistic methods to identify the parameters that most significantly affect the performance outcome; however, it does not consider coupled relationships for multiple output measures. Principal component analysis (PCA) has been applied to characterize common modes of variation in shape and kinematics. In this study, a novel, combined probabilistic and PCA approach was developed to characterize relationships between multiple input parameters and output measures. To demonstrate the benefits of the approach, it was applied to implanted patellofemoral (PF) mechanics to characterize relationships between femoral and patellar component alignment and loading and the resulting joint mechanics. Prior studies assessing PF sensitivity have performed individual perturbation of alignment parameters. However, the probabilistic and PCA approach enabled a more holistic evaluation of sensitivity, including identification of combinations of alignment parameters that most significantly contributed to kinematic and contact mechanics outcomes throughout the flexion cycle, and the predictive capability to estimate joint mechanics based on alignment conditions without requiring additional analysis. The approach showed comparable results for Monte Carlo sampling with 500 trials and the more efficient Latin Hypercube sampling with 50 trials. The probabilistic and PCA approach has broad applicability to biomechanical analysis and can provide insight into the interdependencies between implant design, alignment and the resulting mechanics. [ABSTRACT FROM AUTHOR]

Finite element methods have been applied to evaluate in vivo joint behavior, new devices, and surgical techniques but have typically been applied to a small or single subject cohort. Anatomic variability necessitates the use of many subject-specific models or probabilistic methods in order to adequately evaluate a device or procedure for a population. However, a fully deformable finite element model can be computationally expensive, prohibiting large multisubject or probabilistic analyses. The aim of this study was to develop a group of subject-specific models of the patellofemoral joint and evaluate trade-offs in analysis time and accuracy with fully deformable and rigid body articular cartilage representations. Finite element models of eight subjects were used to tune a pressure-overclosure relationship during a simulated deep flexion cycle. Patellofemoral kinematics and contact mechanics were evaluated and compared between a fully deformable and a rigid body analysis. Additional eight subjects were used to determine the validity of the rigid body pressure-overclosure relationship as a subject-independent parameter. There was good agreement in predicted kinematics and contact mechanics between deformable and rigid analyses for both the tuned and test groups. Root mean square differences in kinematics were less than 0.5 deg and 0.2 mm for both groups throughout flexion. Differences in contact area and peak and average contact pressures averaged 5.4%, 9.6%, and 3.8%, respectively, for the tuned group and 6.9%, 13.1%, and 6.4%, respectively, for the test group, with no significant differences between the two groups. There was a 95% reduction in computational time with the rigid body analysis as compared with the deformable analysis. The tuned pressure-overclosure relationship derived from the patellofemoral analysis was also applied to tibiofemoral (TF) articular cartilage in a group of eight subjects. Differences in contact area and peak and average contact pressures averaged 8.3%, 11.2%, and 5.7% between rigid and deformable analyses in the tibiofemoral joint. As statistical, probabilistic, and optimization techniques can require hundreds to thousands of analyses, a viable platform is crucial to component evaluation or clinical applications. The computationally efficient rigid body platform described in this study may be integrated with statistical and probabilistic methods and has potential clinical application in understanding in vivo joint mechanics on a subject-specific or population basis. [ABSTRACT FROM AUTHOR]

Abstract: This study defines, in the context of unicompartmental tibial replacement, the medial and lateral resection surfaces of 34 tibiae at a depth of 5 mm below the articular surface. Using statistical techniques, three optimal theoretical size and shape unicompartmental tibial designs, (i) implants of consistent shape in varying size (ii) implants symmetric about their ML axis; (iii) implants of varying size and shape, were constructed to best fit the population. Two currently available commercial implants, the Preservation Uni System (DePuy Orthopaedics Inc., Warsaw, IN) and the LCS Uni System (DePuy Orthopaedics Inc., Warsaw, IN), which were similar to types (i) and (ii) respectively, of the theoretical designs, were also included in the analysis. All implants, commercial and theoretical, were compared with one another to determine which implant designs gave the best cortical bone coverage on both the medial and lateral compartments. Of the commercial implants, the type (i) design fitted best, with an average of 67% of the implant edge lying on cortical bone, compared with 57% for the type (ii) implants. Of the theoretical implants, 72%, 67% and 76% of the implant edge lay on cortical bone for types (i), (ii) and (iii) designs, respectively, indicating that there is room for improvement in current implant designs to achieve better coverage in both the medial and lateral compartments combined. [Copyright &y& Elsevier]

Abstract: An accurate and repeatable tibial measurement system will aid in the definition of tibial geometry and improving tibial prosthesis design. Unlike in the femur, there is no standardized method for constructing a tibial coordinate frame. Most tibial measurements are given relative to femoral axes or the coordinate frame of the CT/MRI scanner or radiograph machine. The objective of this study was to establish an independent tibial coordinate frame. Data consisted of CT scans from 34 subjects. The tibial anatomical axis was chosen as the axial axis. The anteroposterior (AP) axis was selected to be parallel to the lateral surface of the tibial shaft and orthogonal to the anatomical axis and from this the mediolateral axis could be derived. The selected AP axis was compared with the surgical tibial AP axis by measuring their variability relative to a common axis, the posterior tibial condylar line (PTCL). The mean angle between the selected AP axis and the perpendicular to the PTCL was measured as −4.07°, standard deviation of 4.28°. The mean angle between the surgical AP axis and the perpendicular to the PTCL was measured as −18.56°, standard deviation of 4.66°. There was no significant difference in the variance of the two sets of measurements (p =0.63). Variability of the selected AP axis was even smaller (standard deviation of 2.74°) when measured independently from the PTCL reference axis, by aligning virtual resection profiles. Anatomically, the selected AP axis was almost perpendicular to the posterior tibial condylar axis. This coordinate system can aid in gathering consistent and repeatable anthropometric data that can be used to improve tibial implant design and could also, in combination with CT/MR imaged-based computer assisted surgery, be used as a guideline for tibial component positioning in TKR. [Copyright &y& Elsevier]

While it is well‐established that early detection and initiation of treatment of developmental dysplasia of the hip (DDH) is crucial to successful clinical outcomes, research on the mechanics of the hip joint during healthy and pathological hip development in infants is limited. Quantification of mechanical behavior in both the healthy and dysplastic developing joints may provide insight into the causes of DDH and facilitate innovation in treatment options. In this study, subject‐specific three‐dimensional finite element models of two pigs were developed: one healthy pig and one pig with induced dysplasia in the right hindlimb. The objectives of this study were: (1) to characterize mechanical behavior in the acetabular articular cartilage during a normal walking cycle by analyzing six metrics: contact pressure, contact area, strain energy density, von Mises stress, principal stress, and principal strain; and (2) to quantify the effect on joint mechanics of three anatomic abnormalities previously identified as related to DDH: variation in acetabular coverage, morphological changes in the femoral head, and changes in the articular cartilage. All metrics, except the contact area, were elevated in the dysplastic joint. Morphological changes in the femoral head were determined to be the most significant factors in elevating contact pressure in the articular cartilage, while the effects of acetabular coverage and changes in the articular cartilage were less significant. The quantification of the pathomechanics of DDH in this study can help identify key mechanical factors that restore normal hip development and can lead to mechanics‐driven treatment options. [ABSTRACT FROM AUTHOR]

Stress fracture is a concern among older adults, as age-related decrements in ankle neuromuscular function may impair their ability to attenuate tibial compressive forces experienced during daily locomotor tasks, such as stair descent. Yet, it is unknown if older adults exhibit greater tibial compression than their younger counterparts when descending stairs. Do older adults exhibit differences in ankle biomechanics that alter their tibial compression during stair descent compared to young adults, and is there a relation between tibial compression and specific changes in ankle biomechanics? Thirteen young (18–25 years) and 13 older (> 65 years) adults had ankle joint biomechanics and tibial compression quantified during a stair descent. Discrete ankle biomechanics (peak joint angle and moment, and joint stiffness) and tibial compression (maximum and impulse) measures were submitted to an independent t-test, while ankle joint angle and moment, and tibial compression waveforms were submitted to an independent statistical parametric mapping t-test to determine group differences. Pearson correlation coefficients (r) determined the relation between discrete ankle biomechanics and tibial compression measures for all participants, and each group. Older adults exhibited smaller maximum tibial compression (p = 0.004) from decreases in peak ankle joint angle and moment between 17 % and 34 % (p = 0.035), and 20–31 % of stance (p < 0.001) than young adults. Ankle biomechanics exhibited a negligible to weak correlation with tibial compression for all participants, with peak ankle joint moment and maximum tibial compression (r = -0.48 ± 0.32) relation the strongest. Older adults typically exhibited a stronger relation between ankle biomechanics and tibial compression (e.g., r = -0.48 ± 0.47 vs r = -0.27 ± 0.52 between peak ankle joint moment and maximum tibial compression). Older adults altered ankle biomechanics and decreased maximum tibial compression to safely execute the stair descent. Yet, specific alterations in ankle biomechanics could not be identified as a predictor of changes in tibial compression. • Older adults altered their ankle to safely execute the stair descent. • Older adults' maximum tibial compression was ∼ 15 % smaller than young adults. • No specific ankle biomechanical measure exhibited a strong relation to tibial compression. [ABSTRACT FROM AUTHOR]

Abstract This paper presents a novel computational framework for neural-driven finite element muscle models, with an application to amyotrophic lateral sclerosis (ALS). The multiscale neuromusculoskeletal (NMS) model incorporates physiologically accurate motor neurons, 3D muscle geometry, and muscle fiber recruitment. It successfully predicts healthy muscle force and tendon elongation and demonstrates a progressive decline in muscle force due to ALS, dropping from 203 N (healthy) to 155 N (120 days after ALS onset). This approach represents a preliminary step towards developing integrated neural and musculoskeletal simulations to enhance our understanding of neurodegenerative and neurodevelopmental conditions through predictive NMS models. [ABSTRACT FROM AUTHOR]

Abstract: In vitro pre-clinical testing of total knee replacement (TKR) devices is a necessary step in the evaluation of new implant designs. Whole joint knee simulators, like the Kansas knee simulator (KKS), provide a controlled and repeatable loading environment for comparative evaluation of component designs or surgical alignment under dynamic conditions. Experimental testing, however, is time and cost prohibitive for design-phase evaluation of tens or hundreds of design variations. Experimentally-verified computational models provide an efficient platform for analysis of multiple components, sizes, and alignment conditions. The purpose of the current study was to develop and verify a computational model of a dynamic, whole joint knee simulator. Experimental internal–external and valgus–varus laxity tests, followed by dynamic deep knee bend and gait simulations in the KKS were performed on three cadaveric specimens. Specimen-specific finite element (FE) models of posterior-stabilized TKR were created from magnetic resonance images and CAD geometry. The laxity data was used to optimize mechanical properties of tibiofemoral soft-tissue structures on a specimen-specific basis. Each specimen was subsequently analyzed in a computational model of the experimental KKS, simulating both dynamic activities. The computational model represented all joints and actuators in the experimental setup, including a proportional-integral-derivative (PID) controller to drive quadriceps actuation. The computational model was verified against six degree-of-freedom patellofemoral (PF) and tibiofemoral (TF) kinematics and actuator loading during both deep knee bend and gait activities, with good agreement in trends and magnitudes between model predictions and experimental kinematics; differences were less than 1.8mm and 2.2° for PF and TF translations and rotations. The whole joint FE simulator described in this study can be applied to investigate a wide range of clinical and research questions. [Copyright &y& Elsevier]

Background: Principal component analysis (PCA) enables the building of statistical shape models of bones and joints. This has been used in conjunction with computer assisted surgery in the past. However, PCA of the clavicle has not been performed. Using PCA, we present a novel method that examines the major modes of size and three-dimensional shape variation in male and female clavicles and suggests a method of grouping the clavicle into size and shape categories. Materials and methods: Twenty-one high-resolution computerized tomography scans of the clavicle were reconstructed and analyzed using a specifically developed statistical software package. After performing statistical shape analysis, PCA was applied to study the factors that account for anatomical variation. Results: The first principal component representing size accounted for 70.5 percent of anatomical variation. The addition of a further three principal components accounted for almost 87 percent. Using statistical shape analysis, clavicles in males have a greater lateral depth and are longer, wider and thicker than in females. However, the sternal angle in females is larger than in males. PCA confirmed these differences between genders but also noted that men exhibit greater variance and classified clavicles into five morphological groups. Discussion And Conclusions: This unique approach is the first that standardizes a clavicular orientation. It provides information that is useful to both, the biomedical engineer and clinician. Other applications include implant design with regard to modifying current or designing future clavicle fixation devices. Our findings support the need for further development of clavicle fixation devices and the questioning of whether gender-specific devices are necessary. [ABSTRACT FROM AUTHOR]

Lipid microencapsulation of Mycobacterium bovis bacille Calmette–Guérin (BCG) produces an oral delivery vaccine that can establish systemic cell-mediated immune reactivity and protection against aerosol mycobacterial challenge in mice. Here, we describe the lymphatic and mucosal sites of bacterial replication, and location of Mycobacterium-specific IFN-γ-secreting cell populations, following oral vaccination of BALB/c mice. Eight weeks following a single oral dose of lipid-encapsulated BCG, viable BCG organisms were recovered from the mesenteric lymph nodes (MLN) of 11/12 mice investigated (93%). Live bacteria were also occasionally recovered from the cervical lymph nodes (17%) and Peyer's patches (8%), but not from homogenates of the lungs or spleen. Strong Mycobacterium-specific IFN-γ production was recorded among isolated splenocytes, but not among populations of mononuclear cells derived from the MLN or lungs. Oral vaccination of mice with lipid-encapsulated BCG thus appears to promote a state of systemic immunological reactivity more akin to that observed following parenteral rather than conventional oral vaccination, despite the fact that replicating bacilli are restricted to lymphatic tissues of the alimentary tract. Possible patterns of lymphocyte sensitization and trafficking are discussed. [ABSTRACT FROM AUTHOR]

Nuclear mechanics is emerging as a key component of stem cell function and differentiation. While changes in nuclear structure can be visually imaged with confocal microscopy, mechanical characterization of the nucleus and its sub-cellular components require specialized testing equipment. A computational model permitting cell-specific mechanical information directly from confocal and atomic force microscopy of cell nuclei would be of great value. Here, we developed a computational framework for generating finite element models of isolated cell nuclei from multiple confocal microscopy scans and simple atomic force microscopy (AFM) tests. Confocal imaging stacks of isolated mesenchymal stem cells were converted into finite element models and siRNA-mediated Lamin A/C depletion isolated chromatin and Lamin A/C structures. Using AFM-measured experimental stiffness values, a set of conversion factors were determined for both chromatin and Lamin A/C to map the voxel intensity of the original images to the element stiffness, allowing the prediction of nuclear stiffness in an additional set of other nuclei. The developed computational framework will identify the contribution of a multitude of sub-nuclear structures and predict global nuclear stiffness of multiple nuclei based on simple nuclear isolation protocols, confocal images and AFM tests. [ABSTRACT FROM AUTHOR]

Neuromusculoskeletal (NMS) models can aid in studying the impacts of the nervous and musculoskeletal systems on one another. These computational models facilitate studies investigating mechanisms and treatment of musculoskeletal and neurodegenerative conditions. In this study, we present a predictive NMS model that uses an embedded neural architecture within a finite element (FE) framework to simulate muscle activation. A previously developed neuromuscular model of a motor neuron was embedded into a simple FE musculoskeletal model. Input stimulation profiles from literature were simulated in the FE NMS model to verify effective integration of the software platforms. Motor unit recruitment and rate coding capabilities of the model were evaluated. The integrated model reproduced previously published output muscle forces with an average error of 0.0435 N. The integrated model effectively demonstrated motor unit recruitment and rate coding in the physiological range based upon motor unit discharge rates and muscle force output. The combined capability of a predictive NMS model within a FE framework can aid in improving our understanding of how the nervous and musculoskeletal systems work together. While this study focused on a simple FE application, the framework presented here easily accommodates increased complexity in the neuromuscular model, the FE simulation, or both. [ABSTRACT FROM AUTHOR]

Tensile testing is an essential experiment to assess the mechanical integrity of musculoskeletal soft tissues, yet standard test methods have not been developed to ensure the quality and reproducibility of these experiments. The ASTM International standards organization has created tensile test standards for common industry materials that specify geometric dimensions of test specimens (coupons) that promote valid failures within the gage section (midsubstance), away from the grips. This study examined whether ASTM test standards for plastics, elastomers, and fiber-reinforced composites are suitable for tensile testing of bovine meniscus along the circumferential fiber direction. We found that dumbbell (DB) shaped coupons based on ASTM standards for elastomers and plastics had an 80% and 60% rate of midsubstance failures, respectively. The rate of midsubstance failures dropped to 20% when using straight (ST) coupons based on ASTM standards for fiber-reinforced composites. The mechanical properties of dumbbell shaped coupons were also significantly greater than straight coupons. Finite element models of the test coupons revealed stress distributions that supported our experimental findings. In addition, we found that a commercial deli-slicer was able to slice meniscus to uniform layer thicknesses that were within ASTM dimensional tolerances. This study provides methods, recommendations, and insights that can advance the standardization of tensile testing in meniscus and other soft fibrous tissues. [ABSTRACT FROM AUTHOR]

Differences in patient anatomy are known to influence joint mechanics. Accordingly, intersubject anatomical variation is an important consideration when assessing the design of joint replacement implants. The objective of this study was to develop a computational workflow to perform population-based evaluations of total knee replacement implant mechanics considering variation in patient anatomy and to assess the potential for an efficient sampling strategy to support design phase screening analyses. The approach generated virtual subject anatomies using a statistical shape model of the knee and performed virtual implantation to size and align the implants. A finite-element analysis simulated a deep knee bend activity and predicted patellofemoral (PF) mechanics. The study predicted bounds of performance for kinematics and contact mechanics and investigated relationships between patient factors and outputs. For example, the patella was less flexed throughout the deep knee bend activity for patients with an alta patellar alignment. The results also showed the PF range of motions in AP and ML were generally larger with increasing femoral component size. Comparison of the 10–90% bounds between sampling strategies agreed reasonably, suggesting that Latin Hypercube sampling can be used for initial screening evaluations and followed up by more intensive Monte Carlo simulation for refined designs. The platform demonstrated a functional workflow to consider variation in joint anatomy to support robust implant design. [ABSTRACT FROM AUTHOR]

Patellar dislocation is a debilitating injury common in active adolescents and young adults. Conservative treatment after initial dislocation is often recommended, but almost half of these patients continue to suffer from recurrent dislocation. The objective of this study was to compare preoperative patellofemoral joint stability with stability after a series of simulated procedures, including restorative surgery to correct to pre‐injury state, generic tibial tubercle osteotomy, patient‐specific reconstructive surgery to correct anatomic abnormality, less invasive patient‐specific surgery, and equivalent healthy controls. Three‐dimensional, subject‐specific finite element models of the patellofemoral joint were developed for 28 patients with recurrent patellar dislocation. A 50 N lateral load was applied to the patella to assess the lateral stability of the patellofemoral joint at 10° intervals from 0° to 40° flexion. Medial patellofemoral ligament reconstruction, along with reconstructive procedures to correct anatomic abnormality were simulated. Of all the simulations performed, the healthy equivalent control models showed the least patellar internal–external rotation, medial–lateral translation, and medial patellofemoral ligament restraining load during lateral loading tests. Isolated restorative medial patellofemoral ligament reconstruction was the surgery that resulted in the most patellar internal–external rotation, medial–lateral translation, and medial patellofemoral ligament reaction force across all flexion angles. Patient‐specific reconstruction to correct anatomic abnormality was the only surgical group to have non‐significantly different results compared with the healthy equivalent control group across all joint stability metrics evaluated. Statement of clinical significance: This study suggests patient‐specific reconstructive surgery that corrects underlying anatomic abnormalities best reproduces the joint stability of an equivalent healthy control when compared with the pre‐injury state, generic tibial tubercle osteotomy, and less invasive patient‐specific surgery. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:768‐776, 2020 [ABSTRACT FROM AUTHOR]

Outcomes of total knee arthroplasty (TKA) are dependent on surgical technique, patient variability, and implant design. Non-optimal design or alignment choices may result in undesirable contact mechanics and joint kinematics, including poor joint alignment, instability, and reduced range of motion. Implant design and surgical alignment are modifiable factors with potential to improve patient outcomes, and there is a need for robust implant designs that can accommodate patient variability. Our objective was to develop a statistical shape-function model (SFM) of a posterior stabilized implanted knee to instantaneously predict joint mechanics in an efficient manner. Finite element methods were combined with Latin hypercube sampling and regression analyses to produce modeling equations relating nine implant design and six surgical alignment parameters to tibiofemoral (TF) joint mechanics outcomes during a deep knee bend. A SFM was developed and TF contact mechanics, kinematics, and soft tissue loads were instantaneously predicted from the model. Average normalized root-mean-square error predictions were between 2.79% and 9.42%, depending on the number of parameters included in the model. The statistical shape-function model generated instantaneous joint mechanics predictions using a maximum of 130 training simulations, making it ideally suited for integration into a patient-specific design and alignment optimization pipeline. Such a tool may be used to optimize kinematic function to achieve more natural motion or minimize implant wear, and may aid the engineering and clinical communities in improving patient satisfaction and surgical outcomes. [ABSTRACT FROM AUTHOR]

Over 36 million adults over 65 years of age experience accidental falls each year. The underlying neuromechanics (whole-body function) and driving forces behind accidental falls, as well as the effects of aging on the ability of the musculoskeletal system to adapt, are poorly understood. We evaluated differences in kinematics (lower extremity joint angles and range of motion), kinetics (ground reaction force), and electromyography (muscle co-contraction), due to changes in surface conditions during gait in 14 older adults with a history of falling and 14 young adults. We investigated the impact of challenging surfaces on musculoskeletal adaptation and compared the mechanisms of adaptation between age-groups. Older adults displayed greater hip and knee flexion and range of motion during gait, reduced initial vertical loading, and 13 % greater knee muscle co-contraction during early stance compared to young adults. Across age groups, the presence of an uneven challenging surface increased lower-limb flexion compared to an even surface. On a slick surface, older adults displayed 30 % greater ankle muscle co-contraction during early stance as compared to young adults. Older adults respond to challenging surfaces differently than their younger counterparts, employing greater flexion during early stance. This study underscores the need for determining lower-limb musculoskeletal adaptation strategies during gait and assessing how these strategies change with age, risk of accidental falls, and environmental surfaces to reduce the risk of accidental falls. [ABSTRACT FROM AUTHOR]

ABSTRACT Understanding the mechanical loading environment and resulting joint mechanics for activities of daily living in total knee arthroplasty is essential to continuous improvement in implant design. Although survivorship of these devices is good, a substantial number of patients report dissatisfaction with the outcome of their procedure. Knowledge of in vivo kinematics and joint loading will enable improvement in preclinical assessment and refinement of implant geometry. The purpose of this investigation was to describe the mechanics of total knee arthroplasty during a variety of activities of daily living (gait, walking down stairs, and chair rise/sit). Estimates of muscle forces, tibial contact load, location, and pressure distribution was performed through a combination of mobile fluoroscopy data collection, musculoskeletal modeling, and finite element simulation. For the activities evaluated, joint compressive load was greatest during walking down stairs; however, the highest contact pressure occurred during chair rise/sit. The joint contact moment in the frontal plane was mainly varus for gait and walking down stairs, while it was valgus during chair rise/sit. Excursion of the center of pressure on the tibial component was similar during each activity and between the medial and lateral sides. The main determinants of center of pressure location were internal-external rotation, joint load, and tibial insert conformity. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1576-1587, 2016. [ABSTRACT FROM AUTHOR]

Modeling complex knee biomechanics is a continual challenge, which has resulted in many models of varying levels of quality, complexity, and validation. Beyond modeling healthy knees, accurately mimicking pathologic knee mechanics, such as after cruciate rupture or meniscectomy, is difficult. Experimental tests of knee laxity can provide important information about ligament engagement and overall contributions to knee stability for development of subject-specific models to accurately simulate knee motion and loading. Our objective was to provide combined experimental tests and finite-element (FE) models of natural knee laxity that are subject-specific, have one-to-one experiment to model calibration, simulate ligament engagement in agreement with literature, and are adaptable for a variety of biomechanical investigations (e.g., cartilage contact, ligament strain, in vivo kinematics). Calibration involved perturbing ligament stiffness, initial ligament strain, and attachment location until model-predicted kinematics and ligament engagement matched experimental reports. Errors between model-predicted and experimental kinematics averaged <2 deg during varus-valgus (W) rotations, <6 deg during internal-external (IE) rotations, and <3 mm of translation during anterior-posterior (AP) displacements. Engagement of the individual ligaments agreed with literature descriptions. These results demonstrate the ability of our constraint models to be customized for multiple individuals and simultaneously call attention to the need to verify that ligament engagement is in good general agreement with literature. To facilitate further investigations of subject-specific or population based knee joint biomechanics, data collected during the experimental and modeling phases of this study are available for download by the research community. [ABSTRACT FROM AUTHOR]

ABSTRACT Experimental testing of orthopaedic implants requires simplifications concerning load application and activities being analyzed. This computational study investigated how these simplifications affect micromotions at the bone-implant interface of an uncemented femoral knee implant. As a basis, validated in vivo loads of the stance phase of gait and a deep knee bend were adopted. Eventually, three configurations were considered: (i) simulation of the complete loading cycle; (ii) inclusion of only tibiofemoral loads (ignoring patellofemoral loads); and (iii) applying only a single peak tibiofemoral force. For all loading conditions the largest micromotions found at the proximal anterior flange. Without the patellofemoral force, peak micromotions increased 6% and 22% for gait and deep knee bend, respectively. By applying a single peak tibiofemoral force micromotions were overestimated. However, the peak micromotions corresponded to the maximum tibiofemoral force, and strong micromotion correlations were found between a complete loading cycle and a single peak load ( R2 = 0.73 and R2 = 0.89 for gait and deep knee bend, respectively). Deep knee bend resulted in larger micromotions than gait. Our study suggests that a simplified peak force can be used to assess the stability of cementless femoral components. For more robust testing, implants should be subjected to different loading modes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:812-819, 2016. [ABSTRACT FROM AUTHOR]

Healthy patellofemoral (PF) joint mechanics are critical to optimal function of the knee joint. Patellar maltracking may lead to large joint reaction loads and high stresses on the articular cartilage, increasing the risk of cartilage wear and the onset of osteoarthritis. While the mechanical sources of PF joint dysfunction are not well understood, links have been established between PF tracking and abnormal kinematics of the tibiofemoral (TF) joint, specifically following cruciate ligament injury and repair. The objective of this study was to create a validated finite element (FE) representation of the PF joint in order to predict PF kinematics and quadriceps force across healthy and pathological specimens. Measurements from a series of dynamic in-vitro cadaveric experiments were used to develop finite element models of the knee for three specimens. Specimens were loaded under intact, ACL-resected and both ACL and PCL-resected conditions. Finite element models of each specimen were constructed and calibrated to the outputs of the intact knee condition, and subsequently used to predict PF kinematics, contact mechanics, quadriceps force, patellar tendon moment arm and patellar tendon angle of the cruciate resected conditions. Model results for the intact and cruciate resected trials successfully matched experimental kinematics (avg. RMSE 4.0°, 3.1 mm) and peak quadriceps forces (avg. difference 5.6%). Cruciate resections demonstrated either increased patellar tendon loads or increased joint reaction forces. The current study advances the standard for evaluation of PF mechanics through direct validation of cruciate-resected conditions including specimen-specific representations of PF anatomy. [ABSTRACT FROM AUTHOR]

Painful patellar crepitus is a potential complication in up to 14% of patients following posterior-stabilized (PS) total knee arthroplasty (TKA). A recent clinical study identified influential patient and surgical variables by comparing a group of crepitus patients with controls matched for age, sex, and body mass index. The purpose of our study was to evaluate effects of variables identified as significant in the clinical study, including patellar ligament length, femoral component flexion, patellar button size, and position of the joint line, on contact between the quadriceps tendon and the PS femoral component. A previously verified finite element model was utilized to estimate tendo-femoral contact during deep flexion activity. Using discrete perturbations, the computational model confirmed the clinical findings in that an increased patellar ligament length, flexed femoral component, lowered joint line, and larger patellar component all reduced potentially deleterious contact near the intercondylar notch. With the selected level of anatomic and component alignment perturbations, the most influential factor affecting tendo-femoral contact was patellar ligament length. Three crepitus patients with matched controls were subsequently modeled, and contact with the anterior border of the notch was present in each crepitus patient, but none of the controls. Alternative surgical alignments for these patients were evaluated to improve the potential long-term outcomes. By characterizing conditions that may lead to painful crepitus, the modeling approach supports clinicians by identifying pre-surgical indicators and important alignment parameters to control intraoperatively. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1355-1361, 2012 [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is an important disease of low birth-weight neonates. The immaturity of the gut mucosa may result in close contact between the host epithelium and microorganisms which are normally confined to the gut lumen. Damage of the mucosa due to endotoxin, cytokine production or other factors is believed to then occur. The aim of this study was to determine whether spray-dried bovine colostrum demonstrated potential in vitro as a prophylactic for NEC. Antiadherence was measured using a tissue culture assay and antibody levels against Enterobacteriaceae were determined by ELISA. The effect of bovine colostrum on the production of cytokines implicated in NEC was determined by a multiplex bead assay. Enterobacter cloacae, Klebsiella oxytoca, Escherichia coli, Serratia marcescens and Klebsiella pneumoniae ssp. pneumoniae were common in both NEC positive and NEC negative infants and IgA and IgG1 antibodies to these species were present in the bovine colostrum. Pretreatment with bovine colostrum produced a significant decrease ( P<0.001) in attachment of bacteria to HT-29 cells. Bovine colostrum significantly increased the production of IL-8 in HT-29 cells and IL-8, IL-6 and TNF-α in THP-1 cells ( P<0.001). The potential of bovine colostrum to increase the production of inflammatory mediators could limit its usefulness. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a pathological degenerative condition of the joints that is widely prevalent worldwide, resulting in significant pain, disability, and impaired quality of life. The diverse etiology and pathogenesis of OA can explain the paucity of viable preventive and disease-modifying strategies to counter it. Advances in genome-editing techniques may improve disease-modifying solutions by addressing inherited predisposing risk factors and the activity of inflammatory modulators. Recent progress on technologies such as CRISPR/Cas9 and cell-based genome-editing therapies targeting the genetic and epigenetic alternations in OA offer promising avenues for early diagnosis and the development of personalized therapies. The purpose of this literature review was to concisely summarize the genome-editing options against chronic degenerative joint conditions such as OA with a focus on the more recently emerging modalities, especially CRISPR/Cas9. Future advancements in novel genome-editing therapies may improve the efficacy of such targeted treatments. [ABSTRACT FROM AUTHOR]