The influence of design, materials and kinematics on the in vitro wear of total knee replacements

Debris-induced osteolysis due to surface wear of ultra high molecular weight polyethylene (UHMWPE) bearings is a potential long-term failure mechanism of total knee replacements (TKR). This study investigated the effect of prosthesis design, kinematics and bearing material on the wear of UHMWPE bearings using a physiological knee simulator. The use of a curved fixed bearing design with stabilised polyethylene bearings reduced wear in comparison to more flat-on-flat components which were sterilised by gamma irradiation in air. Medium levels of crosslinking further improved the wear resistance of fixed bearing TKR due to resistance to strain softening when subjected to multidirectional motion at the femoral-insert articulating interface. Backside motion was shown to be a contributing factor to the overall rate of UHMWPE wear in fixed bearing components. Wear of fixed bearing prostheses was reduced significantly when anterior-posterior displacement and internal-external rotation kinematics were reduced due to decreased cross shear on the articulating surface and a reduction in AP displacement. Rotating platform mobile bearing prostheses exhibited reduced wear rates in comparison to fixed bearing components in these simulator studies due to redistribution of knee motion to two articulating interfaces with more linear motions at each interface. This was observed in two rotating platform designs with different UHMWPE bearing materials. In knee simulator studies, wear of TKR bearings was dependent on kinematics at the articulating surfaces and the prosthesis design, as well as the type of material.     

Predicting isomorphic residue replacements for protein design

The replaceability of amino acids as reflected in their neighbourhood selectivity is analyzed in this paper. Neighbourhood selectivity was found to be more characteristic of the individual amino acids than the other commonly used parameters. The residue replacement rank obtained was compared with other proposed ranks and was tested on naturally accepted point mutations in homologous proteins.     

Effect of conformity and contact stress on wear in fixed-bearing total knee prostheses

Ultra high molecular weight polyethylene (PE) remains the primary bearing surface of choice in total knee replacements (TKR). Wear is controlled by levels of cross-shear motion and contact stress. The aim of this study was to compare the wear of fixed-bearing total knee replacements with curved and flat inserts and to test the hypothesis that the flat inserts which give higher contact stresses and smaller contact areas would lead to lower levels of surface wear. A low-conforming, high contact stress knee with a low-medium level of cross shear resulted in significantly lower wear rates in comparison to a standard cruciate sacrificing fixed-bearing knee. The low wear solution found in the knee simulator was supported by fundamental studies of wear as a function of pressure and cross shear in the pin on plate system. Current designs of fixed-bearing knees do not offer this low wear solution due to their medium cross shear, moderate conformity and medium contact stress.     

Limited rotation of the mobile-bearing in a rotating platform total knee prosthesis

The hypothesis of this study was that the polyethylene bearing in a rotating platform total knee prosthesis shows axial rotation during a step-up motion, thereby facilitating the theoretical advantages of mobile-bearing knee prostheses. We examined 10 patients with rheumatoid arthritis who had a rotating platform total knee arthroplasty (NexGen LPS mobile, Zimmer Inc. Warsaw, USA). Fluoroscopic data was collected during a step-up motion six months postoperatively. A 3D-2D model fitting technique was used to reconstruct the in vivo 3D kinematics. The femoral component showed more axial rotation than the polyethylene mobile-bearing insert compared to the tibia during extension. In eight knees, the femoral component rotated internally with respect to the tibia during extension. In the other two knees the femoral component rotated externally with respect to the tibia. In all 10 patients, the femur showed more axial rotation than the mobile-bearing insert indicating the femoral component was sliding on the polyethylene of the rotating platform during the step-up motion. Possible explanations are a too limited conformity between femoral component and insert, the anterior located pivot location of the investigated rotating platform design, polyethylene on metal impingement and fibrous tissue formation between the mobile-bearing insert and the tibial plateau.     

Quantifying the competing relationship between durability and kinematics of total knee replacements using multiobjective design optimization and validated computational models

Durability and kinematics are two critical factors which must be considered during total knee replacement (TKR) implant design. It is hypothesized, however, that there exists a competing relationship between these two performance measures, such that improvement of one requires sacrifice with respect to the other. No previous studies have used rigorous and systematic methods to quantify this relationship. During this study, multiobjective design optimization (MOO) using the adaptive weighted sum (AWS) method is used to determine a set of Pareto-optimal implant designs considering durability and kinematics simultaneously. Previously validated numerical simulations and a parametric modeller are used in conjunction with the AWS method in order to generate a durability-versus-kinematics Pareto curve. In terms of kinematics, a design optimized for kinematics alone outperformed a design optimized for durability by 61.8%. In terms of durability, the design optimized for durability outperformed the kinematics-optimized design by 70.6%. Considering the entire Pareto curve, a balanced (1:1) trade-off could be obtained when equal weighting was placed on both performance measures; however improvement of one performance measure required greater sacrifices with respect to the other when the weighting was extremized. For the first time, the competing relationship between durability and kinematics was confirmed and quantified using optimization methods. This information can aid future developments in TKR design and can be expanded to other total joint replacement designs.     

The effect of valgus/varus malalignment on load distribution in total knee replacements

Valgus or varus malpositioning of the tibial component of a total knee implant may cause increased propensity for loosening or implant wear and eventually may lead to revision surgery. The aim of this study was to determine the effect of valgus/varus malalignment on tibio-femoral mechanics during surgical trial reduction and simulated gait loading. In seven cadaver legs, posterior cruciate sparing total knee replacements were implanted and tibial inserts representing a neutral alignment and 3 degrees and 5 degrees varus and valgus alignments were sequentially inserted. Each knee with each insert was loaded in a manner representative of a trial reduction performed during knee surgery and loaded in a physiological knee simulator. Simulated gait performed on the simulator demonstrated that internal/external and adduction/abduction rotations showed statistical changes with some of the angled inserts at different points in the walking cycle. Neither medial/lateral nor anterior/posterior translations changed statistically during simulated walking. The pressure distribution and total load in the medial and lateral compartments of the tibial component changed significantly with as little as a 3 degrees variation in angulation when loaded in a manner representative of a trial reduction or with a knee simulator. These results support the need for precise surgical reconstruction of the mechanical axis of the knee and proper alignment of the tibial component. These results further demonstrate that tibial contact pressures measured during a trial reduction method may be predictive of contact mechanics at the higher loading seen in the knee simulator.     

Ligaments and articular contact guide passive knee flexion

The aim of this study was to test the hypothesis that the coupled features of passive knee flexion are guided by articular contact and by the isometric fascicles of the ACL, PCL and MCL. A three-dimensional mathematical model of the knee was developed, in which the articular surfaces in the lateral and medial compartments and the isometric fascicles in the ACL, PCL and MCL were represented as five constraints in a one degree-of-freedom parallel spatial mechanism. Mechanism analysis techniques were used to predict the path of motion of the tibia relative to the femur. Using a set of anatomical parameters obtained from a cadaver specimen, the model predicts coupled internal rotation and ab/adduction with flexion. These predictions correspond well to measurements of the cadaver specimen’s motion. The model also predicts posterior translation of contact on the tibia with flexion. Although this is a well-known feature of passive knee flexion, the model predicts more translation than has been reported from experiments in the literature. Modelling of uncertainty in the anatomical parameters demonstrated that the discrepancy between theoretical predictions and experimental measurement can be attributed to parameter sensitivity of the model. This study shows that the ligaments and articular surfaces work together to guide passive knee motion. A principal implication of the work is that both articular surface geometry and ligament geometry must be preserved or replicated by surgical reconstruction and replacement procedures to ensure normal knee kinematics and by extension, mechanics.     

Cost-effectiveness of total hip and knee replacements for the Australian population with osteoarthritis: discrete-event simulation model

Background

Osteoarthritis constitutes a major musculoskeletal burden for the aged Australians. Hip and knee replacement surgeries are effective interventions once all conservative therapies to manage the symptoms have been exhausted. This study aims to evaluate the cost-effectiveness of hip and knee replacements in Australia. To our best knowledge, the study is the first attempt to account for the dual nature of hip and knee osteoarthritis in modelling the severities of right and left joints separately.

Methodology/Principal Findings

We developed a discrete-event simulation model that follows up the individuals with osteoarthritis over their lifetimes. The model defines separate attributes for right and left joints and accounts for several repeat replacements. The Australian population with osteoarthritis who were 40 years of age or older in 2003 were followed up until extinct. Intervention effects were modelled by means of disability-adjusted life-years (DALYs) averted. Both hip and knee replacements are highly cost effective (AUD 5,000 per DALY and AUD 12,000 per DALY respectively) under an AUD 50,000/DALY threshold level. The exclusion of cost offsets, and inclusion of future unrelated health care costs in extended years of life, did not change the findings that the interventions are cost-effective (AUD 17,000 per DALY and AUD 26,000 per DALY respectively). However, there was a substantial difference between hip and knee replacements where surgeries administered for hips were more cost-effective than for knees.

Conclusions/Significance

Both hip and knee replacements are cost-effective interventions to improve the quality of life of people with osteoarthritis. It was also shown that the dual nature of hip and knee OA should be taken into account to provide more accurate estimation on the cost-effectiveness of hip and knee replacements.     

The use of animal models to guide rational vaccine design

Although there are several varieties of animal models of tuberculosis, the mouse and the guinea pig are by far the most validated and useful. These provide information about vaccine-induced protection, immunogenicity, toxicity, and immunopathological effects. There is still much to be learned, however, in terms of rational vaccine design, especially in the context of therapeutic or anti-latent vaccine formulations and animal models of these situations.     

The kinetics of oligonucleotide replacements

The formation of a duplex between two nucleic acid strands is restricted if one of the strands forms an intra- or intermolecular secondary structure. The formation of the new duplex requires the dissociation and replacement of the initial structure. To understand the mechanism of this type of kinetics we studied the replacement of a labeled DNA oligonucleotide probe bound to a complementary DNA target with an unlabeled probe of the same sequence. The replacement kinetics were measured using a gel-shift assay for 12, 14 and 16-nucleotide probes as a function of temperature and concentration of the unlabeled probe. The results demonstrate that the overall replacement rate is a combination of two kinetic pathways: dissociative and sequential displacement. The dissociative pathway occurs by the spontaneous dissociation of the initial duplex followed by association of the target and unlabeled probe. The sequential displacement pathway requires only the partial melting of the initial duplex to allow for the formation of a branched nucleation complex with the unlabeled probe, followed by the complete displacement of the labeled probe by migration of the branch point. The contribution from the dissociative pathway is predominant at temperatures close to the melting point of the labeled probe, whereas the contribution from the displacement pathway prevails at lower temperatures and when the concentration of the replacing unlabeled probe is high. The results show that at physiological conditions, duplex formation between a single-stranded oligonucleotide probe and a structured region of a target molecule occurs mainly by the sequential-displacement mechanism.     

Geometry and motion of the knee for implant and orthotic design

By analysing sections of distal femurs in the computer, and by making direct measurements, the posterior femoral condyles were shown to closely fit spherical surfaces. The center of the spheres were then used as reference points and used to define reference axes in a motion study. In flexing from 0 to 120 degrees the medial femoral condyle moved little, the lateral moved posteriorly by 17 mm, and there was an axial rotation of 20 degrees. The data were applied to implant and orthotic design and evaluation.     

Experimental evaluation of an elastic foundation model to predict contact pressures in knee replacements

Computational wear prediction is an attractive concept for evaluating new total knee replacement designs prior to physical testing and implementation. An important hurdle to such technology is the lack of in vivo contact pressure predictions. To address this issue, this study evaluates a computationally efficient simulation approach that combines the advantages of rigid and deformable body modeling. The hybrid method uses rigid body dynamics to predict body positions and orientations and elastic foundation theory to predict contact pressures between general three-dimensional surfaces. To evaluate the method, we performed static pressure experiments with a commercial knee implant in neutral alignment using flexion angles of 0, 30, 60, and 90 degrees and loads of 750, 1500, 2250, and 3000N. Using manufacturer CAD geometry for the same implant, an elastic foundation model with linear or nonlinear polyethylene material properties was implemented within a commercial multibody dynamics software program. The model's ability to predict experimental peak and average contact pressures simultaneously was evaluated by performing dynamic simulations to find the static configuration. Both the linear and nonlinear material models predicted the average contact pressure data well, while only the linear material model could simultaneously predict the trends in the peak contact pressure data. This novel modeling approach is sufficiently fast and accurate to be used in design sensitivity and optimization studies of knee implant mechanics and ultimately wear.     

The design of potent and selective inhibitors of DPP-4: Optimization of ADME properties by amide replacements

For a series of β-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes.     

The effects of knee brace hinge design and placement on joint mechanics

A computer model of 23 knees was obtained by embedding, slicing and digitizing the bone outlines and ligament co-ordinates. Using co-ordinate transformations, various three-dimensional motions were imposed on the knees, and calculations made of femoral-tibial contact error, contact point locations and ligament lengths. Significant deviations in these parameters were noted for abnormal motions including the elimination of internal-external rotation and a-p displacement and the misplacement of a hinge producing correct motion. The resulting mismatch could result in shear in soft tissues, cuff-to-skin slippage and inaccurate ligament length patterns.     

Get ready for the CRISPR/Cas system: A beginner's guide to the engineering and design of guide RNAs

The clustered regularly interspaced short palindromic repeats (CRISPR) system is a state-of-the-art tool for versatile genome editing that has advanced basic research dramatically, with great potential for clinic applications. The system consists of two key molecules: a CRISPR-associated (Cas) effector nuclease and a single guide RNA. The simplicity of the system has enabled the development of a wide spectrum of derivative methods. Almost any laboratory can utilize these methods, although new users may initially be confused when faced with the potentially overwhelming abundance of choices. Cas nucleases and their engineering have been systematically reviewed previously. In the present review, we discuss single guide RNA engineering and design strategies that facilitate more efficient, more specific and safer gene editing.     

Constraints and fixation for implanted joint replacements

Observations made on both cemented and uncemented joint prostheses after about two years of use show a layer of fibrous tissue next to the bone. This fibrous layer smooths over surface features up to l mm in size, and must be assumed to be weak in tension and shear. Prosthesis-bone interfaces should therefore be designed to transmit all forces acting on the prosthesis as compressive stresses. The forces acting across prostheses are controlled by the constraints exerted by the articulating surfaces; if the useful ligaments present are allowed to do their job of transmitting tension, the articulating surfaces can be designed to transmit only such forces and moments as can safely be transmitted across the prosthesis-bone interfaces.     

An energy dissipation and cross shear time dependent computational wear model for the analysis of polyethylene wear in total knee replacements

The cost and time efficiency of computational polyethylene wear simulations may enable the optimization of total knee replacements for the reduction of polyethylene wear. The present study proposes an energy dissipation wear model for polyethylene which considers the time dependent molecular behavior of polyethylene, aspects of tractive rolling and contact pressure. This time dependent – energy dissipation wear model was evaluated, along with several other wear models, by comparison to pin-on-disk results, knee simulator wear test results under various kinematic conditions and knee simulator wear test results that were performed following the ISO 14243-3 standard. The proposed time dependent – energy dissipation wear model resulted in improved accuracy for the prediction of pin-on-disk and knee simulator wear test results compared with several previously published wear models.     

Smart design of fiber optic surfaces for improved plasmonic biosensing

Although the phenomenon of surface plasmon resonance (SPR) is known for more than a century now, traditional prism-based SPR platforms have hardly escaped the research laboratories despite being recognized for the sensitive and specific performance. Significant efforts have been made over the last years to overcome their existing limitations by coupling the SPR phenomenon to the fiber optic (FO) technology. While this platform has been promoted as cost-effective and simpler alternative capable of handling label-free bioassays, quantification and real-time monitoring of biomolecular interactions, examples of its applicability in sensing and biosensing remain to date very limited. The FO-SPR system is still in development and requires further advancements for reaching the stability and sensitivity of the benchmark SPR systems. Among existing strategies for device improvement, those based on modifying the FO tips using nanomaterials are mostly studied. These small-scale objects provide a wide range of possibilities for alternating the architecture of the FO sensitive zone, enabling also unique effects such as localized SPR (LSPR). This mini-review summarizes the latest innovations in the fabrication procedures which use nanoparticles or other nanomaterials, aiming at FO-SPR technology performance improvements, as well as addition of new device features and functionalities.