Modeling of the native knee with kinematic data derived from experiments using the VIVO™ joint simulator: a feasibility study.

BACKGROUND: Despite advances in total knee arthroplasty, many patients are still unsatisfied with the functional outcome. Multibody simulations enable a more efficient exploration of independent variables compared to experimental studies. However, to what extent numerical models can fully reproduce knee joint kinematics is still unclear. Hence, models must be validated with different test scenarios before being applied to biomechanical questions. METHODS: In our feasibility study, we analyzed a human knee specimen on a six degree of freedom joint simulator, applying a passive flexion and different laxity tests with sequential states of ligament resection while recording the joint kinematics. Simultaneously, we generated a subject-specific multibody model of the native tibiofemoral joint considering ligaments and contact between articulating cartilage surfaces. RESULTS: Our experimental data on the sequential states of ligament resection aligned well with the literature. The model-based knee joint kinematics during passive flexion showed good agreement with the experiment, with root-mean-square errors of less than 1.61 mm for translations and 2.1° for knee joint rotations. During laxity tests, the experiment measured up to 8 mm of anteroposterior laxity, while the numerical model allowed less than 3 mm. CONCLUSION: Although the multibody model showed good agreement to the experimental kinematics during passive flexion, the validation showed that ligament parameters used in this feasibility study are too stiff to replicate experimental laxity tests correctly. Hence, more precise subject-specific ligament parameters have to be identified in the future through model optimization.

An implicit divalent counterion force field for RNA molecular dynamics.

How to properly account for polyvalent counterions in a molecular dynamics simulation of polyelectrolytes such as nucleic acids remains an open question. Not only do counterions such as Mg(2+) screen electrostatic interactions, they also produce attractive intrachain interactions that stabilize secondary and tertiary structures. Here, we show how a simple force field derived from a recently reported implicit counterion model can be integrated into a molecular dynamics simulation for RNAs to realistically reproduce key structural details of both single-stranded and base-paired RNA constructs. This divalent counterion model is computationally efficient. It works with existing atomistic force fields, or coarse-grained models may be tuned to work with it. We provide optimized parameters for a coarse-grained RNA model that takes advantage of this new counterion force field. Using the new model, we illustrate how the structural flexibility of RNA two-way junctions is modified under different salt conditions.

Free energy of RNA-counterion interactions in a tight-binding model computed by a discrete space mapping.

The thermodynamic stability of a folded RNA is intricately tied to the counterions and the free energy of this interaction must be accounted for in any realistic RNA simulations. Extending a tight-binding model published previously, in this paper we investigate the fundamental structure of charges arising from the interaction between small functional RNA molecules and divalent ions such as Mg(2+) that are especially conducive to stabilizing folded conformations. The characteristic nature of these charges is utilized to construct a discretely connected energy landscape that is then traversed via a novel application of a deterministic graph search technique. This search method can be incorporated into larger simulations of small RNA molecules and provides a fast and accurate way to calculate the free energy arising from the interactions between an RNA and divalent counterions. The utility of this algorithm is demonstrated within a fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena group I intron, in which it is shown that the counterion-mediated free energy conclusively directs folding into a compact structure.

Exploration of the Advanced VIVOTM Joint Simulator: An In-Depth Analysis of Opportunities and Limitations Demonstrated by the Artificial Knee Joint.

In biomechanical research, advanced joint simulators such as VIVOTM offer the ability to test artificial joints under realistic kinematics and load conditions. Furthermore, it promises to simplify testing with advanced control approaches and the ability to include virtual ligaments. However, the overall functionality concerning specific test setup conditions, such as the joint lubrication or control algorithm, has not been investigated in-depth so far. Therefore, the aim of this study was to analyse the basic functionality of the VIVOTM joint simulator with six degrees of freedom in order to highlight its capabilities and limitations when testing a total knee endoprostheses using a passive flexion-extension movement. For this, different test setup conditions were investigated, e.g., the control method, repeatability and kinematic reproducibility, waveform frequency, lubrication, and implant embedding. The features offered by the VIVOTM joint simulator are useful for testing joint endoprostheses under realistic loading scenarios. It was found that the results were highly influenced by the varying test setup conditions, although the same mechanical load case was analysed. This study highlights the difficulties encountered when using six degrees of freedom joint simulators, contributes to their understanding, and supports users of advanced joint simulators through functional and tribological analysis of joint endoprostheses.

Impact of Structural Compliance of a Six Degree of Freedom Joint Simulator on Virtual Ligament Force Calculation in Total Knee Endoprosthesis Testing.

The AMTI VIVO™ six degree of freedom joint simulator allows reproducible preclinical testing of joint endoprostheses under specific kinematic and loading conditions. When testing total knee endoprosthesis, the articulating femoral and tibial components are each mounted on an actuator with two and four degrees of freedom, respectively. To approximate realistic physiological conditions with respect to soft tissues, the joint simulator features an integrated virtual ligament model that calculates the restoring forces of the ligament apparatus to be applied by the actuators. During joint motion, the locations of the ligament insertion points are calculated depending on both actuators' coordinates. In the present study, we demonstrate that unintended elastic deformations of the actuators due to the specifically high contact forces in the artificial knee joint have a considerable impact on the calculated ligament forces. This study aims to investigate the effect of this structural compliance on experimental results. While the built-in algorithm for calculating the ligament forces cannot be altered by the user, a reduction of the ligament force deviations due to the elastic deformations could be achieved by preloading the articulating implant components in the reference configuration. As a proof of concept, a knee flexion motion with varying ligament conditions was simulated on the VIVO simulator and compared to data derived from a musculoskeletal multibody model of a total knee endoprosthesis.

Multifunctional Hybrid Material for Endoprosthetic Implants Based on Alumina-Toughened Zirconia Ceramics and Additively Manufactured TiNbTa Alloys.

Aseptic implant loosening after a total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear and corrosion products and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia (ATZ) ceramics and additively manufactured Ti-35Nb-6Ta (TiNbTa) alloys, which are joined by a glass solder. The structure of the joint, the static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity with human osteoblasts are characterized. Furthermore, the biomechanical properties of the functional demonstrators of a femoral component for total knee replacements are evaluated. The TiNbTa-ATZ specimens showed a homogenous joint with statistically distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. Shear strengths of 26.4 ± 4.2 MPa and 38.2 ± 14.4 MPa were achieved for the TiNbTa-ATZ and Ti-ATZ specimens, respectively, and they were not significantly affected by the titanium material used, nor by accelerated aging (p = 0.07). All of the specimens survived 107 cycles of shear loading to 10 MPa. Furthermore, the TiNbTa-ATZ did not impair the proliferation and metabolic activity of the human osteoblasts. Functional demonstrators made of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. The biomechanical and biological properties of TiNbTa-ATZ demonstrate potential applications for endoprosthetic implants.

Experimental evaluation of the primary fixation stability of uncemented ceramic hip resurfacing implants.

Hip resurfacing arthroplasty is associated with increased frictional moments compared to standard heads owing to their large diameter. High frictional moments may harbor the risk of the implant loosening if the frictional moments exceed the fixation stability of the hip resurfacing arthroplasty. Therefore, the aim of this experimental study was to evaluate the fixation stability of ceramic hip resurfacing implants through a turn-off test. The test specimens, made of alumina toughened zirconia (ATZ) ceramics with an inner titanium-coated surface and square base bodies for better application to the test setup, were pushed on artificial bone materials until a predefined seating depth was achieved. Thereafter, the specimens were turned off from the artificial bone material by using a lever-arm and the turn-off moments were calculated. The density of the artificial bone material utilized (15 and 25 pcf), the press-fit (0.4 and 0.8 mm) and the size of the test specimens varied. The push-on forces ranged from 0.6 ± 0.1 kN to 5.6 ± 0.5 kN depending on the press-fit and artificial bone material. The turn-off moments relied on the respective press-fit, artificial bone material and size of the specimen. They belonged between the range of 8.5 ± 0.4 Nm and 105.4 ± 0.2 Nm. Most of the previously described frictional moments are lower compared to the turn-off moments determined in this study. However, in the worst-case scenario, the turn-off moments of the hip resurfacing implants may be reduced, especially when the adjacent bone stock has a low mineral density.

Ions and RNAs: Free Energies of Counterion-Mediated RNA Fold Stabilities.

We present an implicit ion model fo the calculation of the electrostatic free energies of RNA conformations in the presence of divalent counterions such as Mg(2+). The model was applied to the native and several non-native structures of the hammerhead ribozyme and the group I intron in Tetrahymena to study the stability of candidate unfolding intermediates. Based on a rigorous statistical mechanical treatment of the counterions that are closely associated with the RNA while handling the rest of the ions in the solution via a mean field theory in the Grand Canonical ensemble, the implicit ion model accurately reproduces the ordering of their free energies, correctly identifying the native fold as the most stable structure out of the other alternatives. For RNA concentrations in the range below 0.1 µM, divalent concentrations of ∼0.5 mM or above, and over a wide range of solvent dielectric constants, the equilibrium number of divalent ions associated with the RNA remains close to what is needed to exactly neutralize the phosphate negative charges, but the stability of compact RNA folds can be reversed when the divalent ion concentration is lower than ∼0.1 mM, causing the number of associated ions to underneutralize the RNA. In addition to calculating counterion-mediated free energies, the model is also able to identify potential high-affinity electronegative ion binding pockets on the RNA. The model can be easily integrated into an all-atom Monte Carlo RNA simulation as an implicit counterion model.