Introduction

Surgeons commonly resect additional distal femur during primary total knee arthroplasty (TKA) to correct a flexion contracture to restore range of motion and knee function. However, the effect of joint line elevation on the resulting TKA kinematics including frontal plane laxity is unclear. Thus, our goal was to quantify the effect of additional distal femoral resection on passive extension and mid-flexion laxity.

INTRODUCTION

Porous metallic materials, due to their capability of tailoring their mechanical properties to those of bone, have been suggested to be utilized in prosthesis to avoid the stress shielding phenomenon¹, believed to increase the risk of implant loosening².

The aim of this work is to obtain the most simplified model possible to simulate the mechanical behavior of a Ti6Al4V porous structure. For this purpose, a beam element model was analyzed and the results were then compared to a 3D-solid model.

Bone is a connective tissue that undergoes constant remodeling. Any disturbances during this process may result in undesired pathological conditions. A single nucleotide substitution (596T-A) in exon eight which leads to a M199K mutation in human RANKL was found to cause osteoclast-poor autosomal recessive osteopetrosis (ARO). Patients with ARO cannot be cured by hematopoietic stem cell transplantation and, without proper treatments, will die in their early age. To date, how this mutation alters RANKL function has not been characterized. We thus hypothesized that hRANKL M199 residue is a structural determinant for normal RANKL-RANK interaction and osteoclast differentiation. By sharing our findings, we aim to achieve an improved clinical outcome in treating bone-related diseases such as osteoporosis, ARO and osteoarthritis. Site-directed mutagenesis was employed to create three rat RANKL mutants, replacing the methionine 200 (human M199 equivalent residue) with either lysine (M200K), alanine (M200A) or glutamic acid (M200E). Recombinant proteins were subsequently purified through affinity chromatography and visualized by Coomassie blue staining and western blot. MTS was carried out before osteoclastogenesis assay in vitro to measure the cellular toxicity. Bone resorption pit assay, immuno-fluorescent staining, luciferase reporter assay, RT-PCR, western blot and calcium oscillation detection were also conducted to explore the biological effect of rRANKL mutants. Computational modeling, thermal Shift Assay, western blot and protein binding affinity experiments were later carried out for structural analyses. rRANKL mutants M200K/A/E showed a drastically reduced ability to induce osteoclast formation and did not demonstrate features of competitive inhibition against wild-type rRANKL. These mutants are all incapable of supporting osteoclastic polarization and bone resorption or activating RANKL-induced osteoclast marker gene transcription. Consistently, they were unable to induce calcium flux, and also showed a diminished induction of IκBa degradation and activation of NF-kB and NFATc1 transcriptional activity. Furthermore, the transcriptional activation of the antioxidant response element (ARE) crucial in modulating oxidative stress and providing cytoprotection was also unresponsive to stimulation with rM200s. Structural analyses showed that rM200 is located in a hydrophobic pocket critical for protein folding. Thermal shift and western blot assays suggested that rM200 mutants formed unstructured proteins, with disturbed trimerisation and the loss of affinity to its intrinsic receptors RANK and OPG. Taken together, we first demonstrates the underlying cause of M199-meidated ARO in a cellular and molecular level by establishing a phenotype in BMMs similar to observed in human samples. Further investigation hints the structural significance of a hydrophobic pocket within the TNF-like region. Combined with pharmaceutical studies on small-molecule drugs, this finding may represent a therapeutic target motif for future development of anti-resorptive treatments

Background. Wear and fatigue damage to polyethylene components remain major factors leading to complications after total knee and unicompartmental arthroplasty. A number of wear simulations have been reported using mechanical test equipment as well as computer models. Computational models of knee wear have generally not replicated experimental wear under diverse conditions. This is partly because of the complexity of quantifying the effect of cross-shear at the articular interface and partly because the results of pin-on-disk experiments cannot be extrapolated to total knee arthroplasty wear. Our premise is that diverse experimental knee wear simulation studies are needed to generate validated computational models. We combined five experimental wear simulation studies to develop and validate a finite-element model that accurately predicted polyethylene wear in high and low crosslinked polyethylene, mobile and fixed bearing, and unicompartmental (UKA) and tricompartmental knee arthroplasty (TKA). Methods. Low crosslinked polyethylene (PE). A finite element analysis (FEA) of two different experimental wear simulations involving TKA components of low crosslinked polyethylene inserts, with two different loading patterns and knee kinematics conducted in an AMTI knee wear simulator: a low intensity and a high intensity. Wear coefficients incorporating contact pressure, sliding distance, and cross-shear were generated by inverse FEA using the experimentally measured volume of wear loss as the target outcome measure. The FE models and wear coefficients were validated by predicting wear in a mobile bearing UKA design. Highly crosslinked polyethylene (XLPE). Two FEA models were constructed involving TKA and UKA XLPE inserts with different loading patterns and knee kinematics conducted in an AMTI knee wear simulator. Wear coefficients were generated by inverse FEA. Results. Predicted wear rates were within 5% of experimental wear rates during validation tests. Unicompartmental mobile bearing back-side wear accounted for 46% of the total wear in the mobile bearing. Wear during the swing phase was 38% to 44% of total wear. Discussion & Conclusions. Crosslinking polyethylene primarily decreased (by nearly 10-fold) the wear generated by cross-shear. This result can be explained by the reduced propensity of crosslinked polyethylene molecules to orient in the dominant direction of sliding. A highly crosslinked fixed-bearing polyethylene insert can provide high wear performance without the increased risk for mobile bearing dislocation. Finite element analysis can be a robust and efficient method for predicting experimental wear. The value of this model is in rapidly conducting screening studies for design development, assessing the effect of varying patient activity, and assessing newer biomaterials. This FEA model was experimentally validated but requires clinical validation

Introduction. Joint mechanics and implant performance have been shown to be sensitive to ligament properties [1]. Computational models have helped establish this understanding, where optimization is typically used to estimate ligament properties for recreation of physically measured specimen-specific kinematics [2]. If available, contact metrics from physical tests could be used to improve the robustness and validity of these predictions. Understanding specimen-specific relationships between joint kinematics, contact metrics, and ligament properties could further highlight factors affecting implant survivorship and patient satisfaction. Instrumented knee implants offer a means to measure joint contact data both in-vivo and intra-operatively, and can also be used in a controlled experimental environment. This study extends on previous work presented at ISTA [3], and the purpose here was to evaluate the use of instrumented implant contact metrics during optimization of ligament properties for two specimens. The overarching goal of this work is to inform clinical joint balancing techniques and identify factors that are critical to implant performance. Methods. Total knee arthroplasties were performed on 4 (two specimens modeled) cadeveric specimens by an experienced orthopaedic surgeon. An instrumented trial implant (VERASENSE, OrthoSensor, Inc., Dania Beach, FL) was used in place of a standard insert. Experimentation was performed using a simVITROTM controlled robotic musculoskeletal simulator (Cleveland Clinic, Cleveland, OH) to apply intra-operative style loading and measure tibiofemoral kinematics. Three successive laxity style tests were performed at 10° knee flexion: anterior-posterior force (±100 N), varus-valgus moment (±5 Nm), and internal-external moment (±3 Nm). Tibiofemoral kinematics and instrumented implant contact metrics were measured throughout testing (Fig. 1). Specimen-specific finite element models were developed for two of the tested specimens and solved using Abaqus/Explicit (Dassault Systèmes). Relevant ligaments and rigid bone geometries were defined using specimen-specific MRIs. Virtual implantation was achieved using registration and each ligament was modeled as a set of nonlinear elastic springs (Fig. 1). Stiffness values were adopted from the literature [2] while the ligament slack lengths served as control variables during optimization. The objective was to minimize the root mean square difference between VERASENSE measured tibiofemoral contact metrics and the corresponding model results (Fig. 1). Results and Discussion. The models for both specimens successfully recreated joint kinematics with average errors less than 4° in rotations, and 3 mm in translations (not shown). Minus a systematic offset in θ for specimen 3, AFD and θ contact kinematics also realized good agreement for both specimens (Fig. 2). Contact forces were generally over-predicted, though both specimens recreated the experimental trends (Fig. 2). The present work shows continued progress towards simulation based tools that can be used for both research and to support the clinical decision making process. A separate ISTA submission presents assessment of these model's predictive capacity, while future work will evaluate additional specimens, and explore the sensitivity to uncertainties in experimental and modeling parameters. Acknowledgements. This work was supported by Orthosensor Inc. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Reverse total shoulder arthroplasty (RTSA) is an increasingly common treatment for osteoarthritic shoulders with irreparable rotator cuff tears. Although very successful in alleviating pain and restoring some function, there is little objective information relating geometric changes imposed by the reverse shoulder and arm function, particularly the moment generating capacity of the shoulder muscles. Recent modeling studies of reverse shoulders have shown significant variation in deltoid muscle moment arms over a typical range of humeral offset locations in shoulders with RTSA. The goal of this study was to investigate the sensitivity of muscle moment arms as a function of varying the joint center and humeral offset in three representative RTSA subjects that spanned the anatomical range from our previous study cohort. We hypothesized there may exist a more beneficial joint implant placement, measured by muscle moment arms, compared to the actual surgical implant configuration. A 12 degree of freedom, subject-specific model was used to represent the shoulders of three patients with RTSA for whom fluoroscopic measurements of scapular and humeral kinematics during abduction had been obtained. The computer model used subject-specific in vivo abduction kinematics and systematically varied humeral offset locations over 1521 different perturbations from the surgical placement to determine moment arms for the anterior, lateral and posterior aspects of the deltoid muscle. The humeral offset was varied from its surgical position ±4 mm in the anterior/posterior direction, ±12mm in the medial/lateral direction, and −10 mm to 14 mm in the superior/inferior direction. The anterior deltoid moment arm varied up to 20 mm with humeral offset and center of rotation variations, primarily in the medial/lateral and superior/inferior directions. Similarly, the lateral deltoid moment arm demonstrated variations up to 20 mm, primarily with humeral offset changes in the medial/lateral and anterior/posterior directions. The posterior deltoid moment arm varied up to 15mm, primarily in early abduction, and was most sensitive to changes of the humeral offset in the superior/inferior direction. The goal of this study was to assess the sensitivity of the deltoid muscle moment arms as a function of joint configuration for existing RTSA subjects. High variations were found for all three deltoid components. Variation over the entire abduction arc was greatest in the anterior and lateral deltoid, while the posterior deltoid moment arm was mostly sensitive to humeral offset changes early in the abduction arc. Moment arm changes of 15–20 mm represent a significant amount of the total deltoid moment arm. This means there is an opportunity to dramatically change the deltoid moment arms through surgical placement of the joint center of rotation and humeral stem. Computational models of the shoulder may help surgeons optimize subject-specific placement of RTSA implants to provide the best possible muscle function, and assist implant designers to configure devices for the best overall performance

Reverse total shoulder arthroplasty (RTSA) is an increasingly common treatment for osteoarthritic shoulders with irreparable rotator cuff tears. Although very successful in alleviating pain and restoring some function there is little objective information relating geometric changes imposed by the reverse shoulder and the moment generating capacity of the shoulder muscles. Recent modeling studies of reverse shoulders have shown significant variation in deltoid muscle moment arms over varied joint centers for shoulders with RTSA. The goal of this study was to investigate the sensitivity of muscle moment arms as a function of varying the joint center in one representative RTSA subject. We hypothesized there may exist a more beneficial joint implant placement, measured by muscle moment arms, compared to the actual surgical implant placement. A 12 degree of freedom, subject-specific model was used to represent the shoulder of a patient with RTSA for whom fluoroscopic measurements of scapular and humeral kinematics during abduction had been obtained. The computer model used these abduction kinematics and systematically varied joint center locations over 1521 different perturbations from the surgical placement to determine moment arms for the anterior, lateral and posterior aspects of the deltoid muscle. The joint center was varied from its surgical position ±4 mm in the anterior/posterior direction, 0–24 mm in the medial/lateral direction, and −10 mm to 14 mm in the superior/inferior direction. The anterior deltoid moment arm varied up to 16mm with center of rotations variations, primarily in the medial/lateral and superior/inferior directions (Figure 2, Table 1(Figure 1)). Similarly, the lateral deltoid moment arm demonstrated variations up to 13 mm, primarily with joint center changes in the anterior/posterior and superior/inferior directions. The posterior deltoid moment arm varied up to 10mm, primarily in early abduction, and was most sensitive to changes of the joint center in demonstrated a sensitivity of 6 mm corresponding to variations in the superior/inferior directions (Figure 2). The goal of this study was to assess the sensitivity of the deltoid muscle moment arms as a function of joint configuration for an existing RTSA subject. High variations were found for all three deltoid components. Variation over the entire abduction arc was greatest in the anterior and lateral deltoid, while the posterior deltoid moment arm was mostly sensitive to joint center changes early in the abduction arc. Moment arm changes of 10–16mm represent a significant amount of the total deltoid moment arm. This means there is an opportunity to dramatically change the deltoid moments arms through surgical placement of the joint center of rotation. Computational models of the shoulder may help surgeons optimize subject-specific placement of RTSA implants to provide the best possible muscle function, and assist implant designers to configure devices for the best overall performance

Introduction. Surface wear of polyethylene is still considered a long-term risk factor for clinical success, particularly as life expectancy and activity levels increase. Computational models have been used extensively for preclinical wear prediction and optimization of total knee replacements (TKR). In most cases, the input wear parameters (wear factors and coefficients) to the computational models have been experimentally measured under average contact stresses to simulate standard activities. These wear studies are not therefore applicable for more adverse conditions that could lead to edge loading and high stress conditions, including higher levels of activities and severe loading conditions. The current study investigated the multidirectional pin-on-plate wear performance of moderately cross-linked ultra-high molecular weight polyethylene (UHMWPE) under high applied nominal contact stress, to be used as inputs to a computational model investigating adverse high stress conditions. Materials/Methods. Moderately cross-linked UHMWPE (GUR_1020,5Mrad gamma irradiation) pins were tested against cobalt–chrome alloy (CoCr) plates in a multidirectional pin-on-plate wear simulator. The CoCr metallic plates were polished to an average surface roughness of 0.01μm. The pin rotation and the plate reciprocation of ±30º and 28mm were in phase, having a common frequency of 1Hz, and resulted in a multidirectional motion at the pin-plate contact surface in a flat-on-flat configuration. Six different pin diameter and applied load combinations were tested, resulting in applied nominal contact stresses from 4 to 80[MPa](Fig.1). Each set was run for 1million cycles in 25% bovine serum as a lubricant. The volumetric wear was calculated from the weight loss measurements using a density 0.93mg/mm. 3. for the UHMWPE material. The wear factor and wear coefficient were calculated as (volumetric wear/(load x sliding distance)) and (volumetric wear/(contact area x sliding distance)) respectively[1]. Statistical analysis of the data was performed in ANOVA and significance was taken at p<0.05. Results. Changing the load from 80 to 216[N] (5mm_pins) and from 212 to 283[N] (3mm_pins), increased the volumetric wear from 1.38±0.12 to 1.66±0.07 and from 0.8±0.12 to 1.03±0.05[mm. 3. ] respectively (mean±95% confidence interval (CI), n=6). However, under the same load of 216N, changing the pin diameter from 5 to 3 [mm] decreased the volumetric wear from 1.66±0.07 to 0.86±0.02[mm. 3. ] (mean±95% CI, n=6) (Fig.1). For stress levels from 4 to 30[MPa] the wear factor significantly decreased from 3.06±0.27 to 0.67±0.11×10. −7. mm. 3. /N.m] (mean±95%CI, n=6, p<0.001). Any further increase in the stress level (up to 80MPa) did not affect the measured wear factor (ANOVA, p=0.44) (Fig.2-a). In contrast, the measured wear coefficient increased from 1.25±0.11 to 4.88±0.14×10. −9. ] (mean±95% CI, n=6, p<0.001) while increasing the stress from 4 to 80[MPa](Fig.2-b). Discussion. For the same level of motion at the contact surfaces, the two main parameters that significantly contributed to the volumetric wear were the applied load and contact area. The measured wear parameters were significantly dependent on the applied nominal contact stress. Future work will consider different motions at the contact surfaces with different degrees of cross-shear. Conclusion. The stress level significantly affected the wear performance of moderately cross-linked UHMWPE in this pin-on-plate configuration. Computational simulations of TKR should therefore account for these effects when considering adverse high stress conditions

Computational modeling has been used to simulate the natural and prosthetic kinematic and kinetic function in an attempt to compare designs and/or predict a desired motion path from a design. The levels of soft tissue can range from basic ligaments (MCL, LCL, and ACL & PCL) to more complex models. The goal of this study was to evaluate the sensitivity of the Posterior Cruciate ligament in a virtual model and its effects on the kinematic outcome in a commercially available and validated kinematics package (KneeSim, LifeModeler San Clemente, CA). Methods:. KneeSIM is a musculoskeletal modeling environment that is built on the foundation of the ADAMS (MSC Software, Santa Ana CA), a rigid body dynamics solver to compute knee kinematics and forces during a deep knee bend. All parameters are customizable and can be altered by the user. Generic three dimensional models of cruciate retaining components of the femoral, tibial, and patellar are available with the software and were used to provide a common reference for the study. The following parameters were modified for each simulation to evaluate the sensitivity of the PCL in the model: 1) Model without PCL, 2) PCL with default properties, 3) PCL Shifted at femoral origin, 7 mm anterior, 7 mm inferior; tibial origin maintained; 4) PCL with increased stiffness properties (2x default), 5) position in the femur and tibia remained default position and 6) PCL with default properties and location, joint line shifted 4 mm superior. The standard output of tracking the flexion facet center (FFC) motion of the medial and lateral condyles was utilized (Figure 1). Results:. Figure 2 and 3 displays the output of the six conditions tested above. Comparing the curves for the medial and lateral motion show different patterns with the lateral point having more posterior translation than the medial. After approximately 95° of flexion, all cases exhibit an anterior translation in the model. This motion was consistent for all test cases. The model showed no difference with motion either with or without the PCL and with changing the stiffness. Altering the location of the PCL on the femoral insertion had the greatest effect on motion, while shifting the joint line superior was second. The shift of the ligament insertion and changing of the joint line results in the ligament being more parallel to the tibial surface which provides resistance to anterior motion or posterior translation. Discussion:. Although the model was able to discern differences, the inability to highlight variation in motion with and without the PCL suggests that the default parameters are not representative of an experimental or clinical setup. Although it is apparent that KneeSim can be used for comparative assessments between designs, simulations should be designed so as to provide similar boundary conditions. Publications (Colwell et al 2011) did successfully use KneeSim to provide a comparative assessment of CR components; however, only after the default model was altered to match the outcome of the experimental rig. Further analysis of the complexities in soft tissue modeling is warranted

Introduction. The input mechanical properties of knee replacement bearing materials, such as elastic modulus and Poisson's ratio, significantly contribute to the accuracy of computational models. They should therefore be determined from independent experimental studies, under similar test conditions to the clinical and experimental conditions, to provide reliability to the models. In most cases, the reported values in the literature for the elastic modulus and Poisson's ratio of the bearing materials have been measured under tensile test conditions, in contrast to the compressive operating conditions of the total knee replacements (TKR). This study experimentally determined the elastic modulus and Poisson's ratio of conventional and moderately cross-linked ultra-high molecular weight polyethylene (UHMWPE) under compressive test conditions. These material parameters will be inputs to future computational models of TKR. Materials/Methods. To determine the Poisson's ratio of the conventional and moderately cross-linked UHMWPE, contact areas of 12mm diameter cylindrical specimens of 10.2mm length were measured experimentally under a compressive displacement of 1mm, at a strain rate of 12mm/min that was held for 10minutes. A computational model was developed in Abaqus, 6.14–1, to simulate this experimental test assuming different values for the Poisson's ratio of the UHMWPE cylindrical specimens. The curve fitted relationship between the computationally predicted contact area and Poisson's ratio was used to calculate the Poisson's ratio of the UHMWPE specimens, using the experimentally measured contact areas. Using a similar approach, the equivalent elastic modulus of the UHMWPE was calculated using the computationally calculated curve fitted contact area-elastic modulus relationship, from the computational simulation of a ball-on-flat compression test, and the experimentally measured contact area from a ball-on-flat dynamic compression test. This experiment used 10mm thick UHMWPE flat specimens against a 63.5mm rigid ball, under a compressive dynamic sinusoidal loading of 250N average load, and 6000 cycles. The applied test conditions maintained the stress level within the reported range for the TKR. Results. The predicted maximum contact stress was 26 and 35 [MPa] for the conventional and moderately cross-linked UHMWPE respectively. The measured Poisson's ratio was 0.33±0.04 (mean ± 95% confidence interval (CI), n=5) and 0.32±0.08 (mean ± 95% CI, n=3) for conventional and moderately cross-linked UHMWPE respectively. The corresponding values for the equivalent elastic modulus were 365±31 and 553±51 [MPa] (mean ± 95% CI, n=3) respectively (Fig.1). Discussion. The Poisson's ratios and elastic moduli for the conventional and moderately cross-linked UHMWPE materials were more than 20% lower than values reported in literature that have been measured under tensile test conditions [1–3]. Computational wear models adopting mechanical properties of the bearing materials delivered under more realistic compressive loading conditions are more appropriate. Conclusion. The current study presented a reverse engineering approach to characterise the mechanical properties of conventional and moderately cross-linked UHMWPE for TKR bearing materials, under realistic compressive test conditions. The measured mechanical properties, were lower than that reported in literature under tensile loading conditions, and should be adopted in future computational models of TKR for a more realistic and robust virtual modelling platform

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities.

Cite this article: Bone Joint Res 2015;4:105–116