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Background and objective: The primary cilium is a small protrusion found on most mammalian cells. It acts as a cellular antenna, being involved in various cell signaling pathways. The length of the primary cilium affects its function. To study the impact of physical or chemical stimuli on cilia, their lengths must be determined easily and reproducibly. Methods: We have developed and evaluated an open-source R package called detectCilia to detect and measure primary cilia automatically. As a case study to demonstrate the capability of our tool, we compared the influence of 4 different cell culture media compositions on the lengths of primary cilia in human chondrocytes. These media compositions include (1) insulin-transferrin-selenium (ITS); (2) ITS and dexamethasone (Dexa); (3) ITS, Dexa, insulin-like growth factor 1 (IGF-1), and transforming growth factor beta 1 (TGF-β1); and (4) fetal bovine serum (FBS). Results: The assessment of detectCilia included a comparison with 2 similar tools: ACDC (Automated Cilia Detection in Cells) and CiliaQ. Several differences and advantages of our package make it a valuable addition to these tools. In the case study, we have observed variations in the ciliary lengths associated with using different media compositions. Conclusions: We conclude that detectCilia can automatically and reproducibly detect and measure primary cilia in confocal microscopy images with low false-positive rates without requiring extensive user interaction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Derotational distal femoral osteotomy (DFO) is the causal treatment for patients with femoral torsional deformity. The fixation is achieved by a unilateral angle‐stable plate. Delayed‐ or non‐unions are one of the main risks of the procedure. An additional contralateral fixation may benefit the outcome. Therefore, we hypothesize that primary stability in DFO can be improved by an additional fixation with a hinge screw or an internal plate. Methods: Derotational DFO was performed in 15 knees and fixed either with an angle‐stable plate only (group 'None'), with an additional lateral screw (group 'Screw') or with an additional lateral plate (group 'Plate'). Biomechanical evaluation was carried out under axial loading of 150 N (partial weight bearing) and 800 N (full weight bearing), followed by internal and external rotation. After linear axial loading in step 1, a cyclic torsional load of 5 Nm was applied under constant axial load in step 2. In step 3, the specimens were unloaded. Micromovements between the distal and proximal parts of the osteotomy were recorded at each step for all specimens. Results: In step 1, the extent of micromovements was highest in group 'None' and lowest in group 'Plate' without being significantly different. In step 2, group 'Plate' showed significantly higher stability, reflected by less rotation and lower micromovements. Increasing the axial load from 150 to 800 N at step 2 resulted in increased stability in all groups but only reached significance in group 'None'. Conclusion: An additional contralateral plate significantly increased stability in derotational DFO compared to the unilateral angle‐stable plate only. Contrary, a contralateral hinge screw did not provide improved stability. Study Design: Experimental study. Level of Evidence: IV. [ABSTRACT FROM AUTHOR]

Accurate detection of implant loosening is crucial for early intervention in total hip replacements, but current imaging methods lack sensitivity and specificity. Vibration methods, already successful in dentistry, represent a promising approach. In order to detect loosening of the total hip replacement, excitation and measurement should be performed intracorporeally to minimize the influence of soft tissue on damping of the signals. However, only implants with a single sensor intracorporeally integrated into the implant for detecting vibrations have been presented in the literature. Considering different mode shapes, the sensor's position on the implant is assumed to influence the signals. In the work at hand, the influence of the position of the sensor on the recording of the vibrations on the implant was investigated. For this purpose, a simplified test setup was created with a titanium rod implanted in a cylinder of artificial cancellous bone. Mechanical stimulation via an exciter attached to the rod was recorded by three accelerometers at varying positions along the titanium rod. Three states of peri-implant loosening within the bone stock were simulated by extracting the bone material around the titanium rod, and different markers were analyzed to distinguish between these states of loosening. In addition, a modal analysis was performed using the finite element method to analyze the mode shapes. Distinct differences in the signals recorded by the acceleration sensors within defects highlight the influence of sensor position on mode detection and natural frequencies. Thus, using multiple sensors could be advantageous in accurately detecting all modes and determining the implant loosening state more precisely. [ABSTRACT FROM AUTHOR]

Proximal femur fracture risk depends on subject-specific factors such as bone mineral density and morphological parameters. Here, we aim to analyze the dependency of the femoral strength on sixteen morphological parameters. Therefore, finite-element analyses of 20 human femurs during stumbling and lateral falls on the hip were conducted. Pearson correlation coefficients were calculated and morphological parameters with significant correlations were examined in principal component analysis and linear regression analysis. The dependency of the fracture strength on morphological parameters was more pronounced during lateral falls on the hip compared to stumbling. Significant correlations were observed between the neck shaft angle (r = −0.474), neck diameter (r = 0.507), the true distance between the femoral head center and femoral shaft axis (r = 0.459), and its projected distance on the frontal plane (r = 0.511), greater trochanter height (r = 0.497), and distance between the femoral head center and a plane parallel to the frontal plane containing the projection of the femoral head center to the femoral neck axis (r = 0.669). Principal component analysis was strongly weighted by parameters defining the lever arm during a lateral fall as well as the loaded cross-section in the femoral neck. [ABSTRACT FROM AUTHOR]

The current reconstructive surgical procedures implemented after the resection of extended bone segments are associated with high complication rates and long-term treatments. By transplanting an autologous, vascularized and stabilized bone segment, these challenges can be managed. Thus, we propose a novel procedure to expand the currently available autologous bone grafts to the dimensions of the recipient bone using an implantable device. The objective of the present study was to characterize the feasibility of developing an implant prototype for fibula expansion in an in vitro model using a porcine fibula. A balloon catheter, as the part of the implant responsible for expansion, was proven to expand while being periodically filled with sodium chloride. Therefore, the expansion of the balloon catheter was analyzed in an experimental test setup with a 3D-printed porcine fibula with a closure film simulating callus formation to simulate the in vivo situation. Our experimental testing proved the successful expansion of the porcine fibula by the balloon catheter. Hence, the feasibility of the concept for subsequent animal testing was confirmed. [ABSTRACT FROM AUTHOR]

A three-dimensional (3D) understanding of muscle attachment footprints became increasingly relevant for musculoskeletal modeling. The established method to project attachments as points ignores patient-specific individuality. Research focuses on investigating certain muscle groups rather than comprehensively studying all muscles spanning a joint. Therefore, we present a reliable method to study several muscle attachments in order to reconstruct the attachment sites in 3D based on CT imaging for future applications in musculoskeletal modeling. For the present feasibility study, 23 knee-related muscle attachments were CT-scanned postmortem from four nonadipose male specimens. For this, the specific muscle attachments were dissected and marked with a barium sulfate containing paint (60 g BaSO4 in 30 mL water and 10 mL acrylic paint). Subsequently, bone geometries and muscle attachments were reconstructed and evaluated from CT datasets. Bone morphology and footprint variations were studied. Exemplarily, variations were high for pes anserinus insertions (mean 56%) and the origins of M. biceps femoris (mean 54%). In contrast, the origins of the vastus muscles as well as the insertion of the Achilles tendon showed low variation (mean 9% and 13%, respectively). Most attachment sites showed variation exceeding the individuality of bone morphology. In summary, the present data were consistent with the few published studies of specific muscle footprints. Our data shed light on the high variability of muscle attachments, which need to be addressed when studying muscle forces and movements through musculoskeletal modeling. This is the first step to achieving a more profound understanding of muscle morphology to be utilized in numerical simulations. [ABSTRACT FROM AUTHOR]

Introduction: The release of mature interleukin (IL-) 1β; from osteoblasts in response to danger signals is tightly regulated by the nucleotide-binding oligomerization domain leucine-rich repeat and pyrin-containing protein 3 (NLRP3) inflammasome. These danger signals include wear products resulting from aseptic loosening of joint arthroplasty. However, inflammasome activation requires two different signals: a nuclear factor-kappa B (NF-ΚB)-activating priming signal and an actual inflammasome-activating signal. Since human osteoblasts react to wear particles via Toll-like receptors (TLR), particles may represent an inflammasome activator that can induce both signals. Methods: Temporal gene expression profiles of TLRs and associated intracellular signaling pathways were determined to investigate the period when human osteoblasts take up metallic wear particles after initial contact and initiate a molecular response. For this purpose, human osteoblasts were treated with metallic particles derived from cobalt-chromium alloy (CoCr), lipopolysaccharides (LPS), and tumor necrosis factor-alpha (TNF) alone or in combination for incubation times ranging from one hour to three days. Shortly after adding the particles, their uptake was observed by the change in cell morphology and spectral data. Results: Exposure of osteoblasts to particles alone increased NLRP3 inflammasome-associated genes. The response was not significantly enhanced when cells were treated with CoCr + LPS or CoCr + TNF, whereas inflammation markers were induced. Despite an increase in genes related to the NLRP3 inflammasome, the release of IL-1β was unaffected after contactwith CoCr particles. Discussion: Although CoCr particles affect the expression of NLRP3 inflammasome-associated genes, a single stimulus was not sufficient to prime and activate the inflammasome. TNF was able to prime the NLRP3 inflammasome of human osteoblasts. [ABSTRACT FROM AUTHOR]

Introduction: The importance of the assembly procedure on the taper connection strength is evident. However, existent surgical technique guides frequently lack comprehensive and precise instructions in this regard. The aim of our experimental study was to evaluate the influence of the surgical technique guide on the femoral head assembly procedure in surgeons with differing levels of experience in total hip arthroplasty. Materials and methods: Twenty-eight participants, divided into four groups based on their lifetime experience in total hip arthroplasty, conducted a femoral head assembly procedure in a simulated intraoperative environment before and after reviewing the surgical technique guide. Demographic information and the number of hammer blows were documented. Hammer velocity and impaction angle were recorded using an optical motion capturing system, while the impaction force was measured using a dynamic force sensor within the impactor. Results: We observed a high variation in the number of hammer blows, maximum force, and impaction angle. Overall, the number of hammer blows decreased significantly from 3 to 2.2 after reviewing the surgical technique guide. The only significant intragroup difference in the number of hammer blows was observed in the group with no prior experience in total hip arthroplasty. No correlation was found between individual factors (age, weight, height) or experience and the measured parameters (velocity, maximum force and angle). Conclusions: The present study demonstrated a high variation in the parameters of the femoral head assembly procedure. Consideration of the surgical technique guide was found to be a limited factor among participants with varying levels of experience in total hip arthroplasty. These findings underline the importance of sufficient preoperative training, to standardize the assembly procedure, including impaction force, angle, and use of instruments. [ABSTRACT FROM AUTHOR]

Cryosectioning is known as a common and well-established histological method, due to its easy accessibility, speed, and cost efficiency. However, the creation of bone cryosections is especially difficult. In this study, a cryosectioning protocol for trabecular bone that offers a relatively cheap and undemanding alternative to paraffin or resin embedded sectioning was developed. Sections are stainable with common histological dying methods while maintaining sufficient quality to answer a variety of scientific questions. Furthermore, this study introduces an automated protocol for analysing such sections, enabling users to rapidly access a wide range of different stainings. Therefore, an automated 'QuPath' neural network-based image analysis protocol for histochemical analysis of trabecular bone samples was established, and compared to other automated approaches as well as manual analysis regarding scattering, quality, and reliability. This highly automated protocol can handle enormous amounts of image data with no significant differences in its results when compared with a manual method. Even though this method was applied specifically for bone tissue, it works for a wide variety of different tissues and scientific questions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Resultant hip joint forces can currently only be recorded in situ in a laboratory setting using instrumented total hip replacements (THRs) equipped with strain gauges. However, permanent recording is important for monitoring the structural condition of the implant, for therapeutic purposes, for self-reflection, and for research into managing the predicted increasing number of THRs worldwide. Therefore, this study aims to investigate whether a recently proposed THR with an integrated piezoelectric element represents a new possibility for the permanent recording of hip joint forces and the physical activities of the patient. Hip joint forces from nine different daily activities were obtained from the OrthoLoad database and applied to a total hip stem equipped with a piezoelectric element using a uniaxial testing machine. The forces acting on the piezoelectric element were calculated from the generated voltages. The correlation between the calculated forces on the piezoelectric element and the applied forces was investigated, and the regression equations were determined. In addition, the voltage outputs were used to predict the activity with a random forest classifier. The coefficient of determination between the applied maximum forces on the implant and the calculated maximum forces on the piezoelectric element was R2 = 0.97 (p < 0.01). The maximum forces on the THR could be determined via activity-independent determinations with a deviation of 2.49 ± 13.16% and activity-dependent calculation with 0.87 ± 7.28% deviation. The activities could be correctly predicted using the classification model with 95% accuracy. Hence, piezoelectric elements integrated into a total hip stem represent a promising sensor option for the energy-autonomous detection of joint forces and physical activities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The additive manufacturing of titanium–niobium–tantalum alloys with nominal chemical compositions Ti–xNb–6Ta (x = 20, 27, 35) by means of laser beam powder bed fusion is reported, and their potential as implant materials is elaborated by mechanical and biological characterization. The properties of dense specimens manufactured in different build orientations and of open porous Ti–20Nb–6Ta specimens are evaluated. Compression tests indicate that strength and elasticity are influenced by the chemical composition and build orientation. The minimum elasticity is always observed in the 90° orientation. It is lowest for Ti–20Nb–6Ta (43.2 ± 2.7 GPa) and can be further reduced to 8.1 ± 1.0 GPa for open porous specimens (p < 0.001). Furthermore, human osteoblasts are cultivated for 7 and 14 days on as-printed specimens and their biological response is compared to that of Ti–6Al–4V. Build orientation and cultivation time significantly affect the gene expression profile of osteogenic differentiation markers. Incomplete cell spreading is observed in specimens manufactured in 0° build orientation, whereas widely stretched cells are observed in 90° build orientation, i.e., parallel to the build direction. Compared to Ti–6Al–4V, Ti–Nb–Ta specimens promote improved osteogenesis and reduce the induction of inflammation. Accordingly, Ti–xNb–6Ta alloys have favorable mechanical and biological properties with great potential for application in orthopedic implants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To obtain bone allografts that are safe for transplantation, several processing steps for decellularization and decontamination have to be applied. Currently available processing methods, although well‐established, may interfere with the biomechanical properties of the bone. High hydrostatic pressure (HHP) is known to devitalize tissues effectively while leaving the extracellular matrix intact. However, little is known about the inactivation of the contaminating microorganisms by HHP. This study aims to investigate the ability of high‐pressure decontamination and to establish a treatment protocol that is able to successfully inactivate microorganisms with the final goal to sterilize bone specimens. Using Escherichia coli (E. coli) as a model organism, HHP treatment parameters like temperature and duration, pressurization medium, and the number of treatment cycles were systematically adjusted to maximize the efficiency of inactivating logarithmic and stationary phase bacteria. Towards that we quantified colony‐forming units (cfu) after treatment and investigated morphological changes via Field Emission Scanning Electron Microscopy (FESEM). Additionally, we tested the decontamination efficiency of HHP in bovine cancellous bone blocks that were contaminated with bacteria. Finally, two further model organisms were evaluated, namely Pseudomonas fluorescens as a Gram‐negative microorganism and Micrococcus luteus as a Gram‐positive representative. A HHP protocol, using 350 MPa, was able to sterilize a suspension of stationary phase E. coli, leading to a logarithmic reduction factor (log RF) of at least −7.99 (±0.43). The decontamination of bone blocks was less successful, indicating a protective effect of the surrounding tissue. Sterilization of 100% of the samples was achieved when a protocol optimized in terms of treatment temperature, duration, pressurization medium, and number and/or interval of cycles, respectively, was applied to bone blocks artificially contaminated with a suspension containing 104 cfu/mL. Hence, we here successfully established protocols for inactivating Gram‐negative model microorganisms by HHP of up to 350 MPa, while pressure levels of 600 MPa were needed to inactivate the Gram‐positive model organism. Thus, this study provides a basis for further investigations on different pathogenic bacteria that could enable the use of HHP in the decontamination of bone grafts intended for transplantation. [ABSTRACT FROM AUTHOR]

To improve the wear resistance of articulating metallic joint endoprostheses, the surfaces can be coated with titanium niobium nitride (TiNbN). Under poor tribological conditions or malalignment, wear can occur on these implant surfaces in situ. This study investigated the biological response of human osteoblasts to wear particles generated from TiNbN‐coated hip implants. Abrasive particles were generated in a hip simulator according to ISO 14242‐1/−2 and extracted with Proteinase K. Particle characteristics were evaluated by electron microscopy and energy dispersive x‐ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP‐MS) and dynamic light scattering (DLS) measurements. Human osteoblasts were exposed to different particle dilutions (1:20, 1:50, and 1:100), and cell viability and gene expression levels of osteogenic markers and inflammatory mediators were analyzed after 4 and 7 days. Using ICP‐MS, EDS, and DLS measurements, ~70% of the particles were identified as TiNbN, ranging from 39 to 94 nm. The particles exhibited a flat and subangular morphology. Exposure to particles did not influence cell viability and osteoblastic differentiation capacity. Protein levels of collagen type 1, osteoprotegerin, and receptor activator of nuclear factor κB ligand were almost unaffected. Moreover, the pro‐inflammatory response via interleukins 6 and 8 was minor induced after particle contact. A high number of TiNbN wear particles only slightly affected osteoblasts' differentiation ability and inflammatory response compared to metallic particles. Nevertheless, further studies should investigate the role of these particles in peri‐implant bone tissue, especially concerning other cell types. [ABSTRACT FROM AUTHOR]

Purpose: Refixation of acute anterior cruciate ligament (ACL) tears represents an increasingly popular treatment option. Systematic evaluations of various suture technique parameters are still pending. We therefore aimed to evaluate the mechanical pull‐out outcomes of various suture methods for optimization of ACL refixation. Methods: Sixty fresh knees from mature domestic pigs were dissected and the femoral attachment of the ACL was peeled off. The 60 knees were divided in 10 groups and sutured as follows: (A) one suture (1, 2, 4 and 6 passes), (B) two sutures (2, 4 and 6 passes each; sutures knotted together as a loop) and (C) two sutures (2, 4 and 6 passes each, sutures knotted separately). The pull‐out test was conducted using a validated electrodynamic testing machine. First occurrence of failure, maximum pull‐out load and stiffness were measured. Suture failure was defined as pull‐out of the ACL. Results: Two‐point fixation, using two sutures, with at least two passes, showed the most favourable biomechanical stability. The maximum pull‐out load was significantly higher with two sutures (529.5 N) used compared to one (310.4 N), p < 0.001. No significant differences were found for maximum pull‐out loads between two‐point fixation versus one‐point fixation but stiffness was significantly higher with two‐point fixation (107.4 N/mm vs. 79.4 N/mm, p < 0.001). More passes resulted in higher maximum pull‐out loads. Conclusion: The results suggest using two independent sutures, refixed separately and at least two suture passes, is appropriate for ACL refixation. More suture passes provide additional strength but are technically challenging to achieve during surgery. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Total hip joint replacement (THR) is clinically well‐established. In this context, the resulting range of motion (ROM) is crucial for patient satisfaction when performing joint movements. However, the ROM for THR with different bone preserving strategies (short hip stem and hip resurfacing) raises the question of whether the ROM is comparable with conventional hip stems. Therefore, this computer‐based study aimed to investigate the ROM and type of impingement for different implant systems. An established framework with computer‐aided design 3D models based on magnetic resonance imaging data of 19 patients with hip osteoarthritis was used to analyse the ROM for three different implant systems (conventional hip stem vs. short hip stem vs. hip resurfacing) during typical joint movements. Our results revealed that all three designs led to mean maximum flexion higher than 110°. However, hip resurfacing showed less ROM (−5% against conventional and −6% against short hip stem). No significant differences were observed between the conventional and short hip stem during maximum flexion and internal rotation. Contrarily, a significant difference was detected between the conventional hip stem and hip resurfacing during internal rotation (p = 0.003). The ROM of the hip resurfacing was lower than the conventional and short hip stem during all three movements. Furthermore, hip resurfacing shifted the impingement type to implant‐to‐bone impingement compared with the other implant designs. The calculated ROMs of the implant systems achieved physiological levels during maximum flexion and internal rotation. However, bone impingement was more likely during internal rotation with increasing bone preservation. Despite the larger head diameter of hip resurfacing, the ROM examined was substantially lower than that of conventional and short hip stem. [ABSTRACT FROM AUTHOR]

Interleukin (IL-) 6 is a critical factor in inflammatory processes of rheumatoid arthritis (RA). This is of high interest as the progression of RA may lead to the implantation of joint endoprostheses, which is associated with a pro-inflammatory increase in IL-6 in the periprosthetic tissue. Biological agents such as sarilumab have been developed to inhibit IL-6-mediated signaling. However, IL-6 signaling blockade should consider the inhibition of inflammatory processes and the regenerative functions of IL-6. This in vitro study investigated whether inhibiting IL-6 receptors can affect the differentiation of osteoblasts isolated from patients with RA. Since wear particles can be generated at the articular surfaces of endoprostheses leading to osteolysis and implant loosening, the potential of sarilumab to inhibit wear particle-induced pro-inflammatory processes should be investigated. Both in monocultures and indirect co-cultures with osteoclast-like cells (OLCs), human osteoblasts were stimulated with 50 ng/mL each of IL-6 + sIL-6R and in combination with sarilumab (250 nM) to characterize cell viability and osteogenic differentiation capacity. Furthermore, the influence of IL-6 + sIL-6R or sarilumab on viability, differentiation, and inflammation was evaluated in osteoblasts exposed to particles. Stimulation with IL-6 + sIL-6R and sarilumab did not affect cell viability. Except for the significant induction of RUNX2 mRNA by IL-6 + sIL-6R and a significant reduction with sarilumab, no effects on cell differentiation and mineralization could be detected. Furthermore, the different stimulations did not affect the osteogenic and osteoclastic differentiation of co-cultured cells. Compared to the osteoblastic monocultures, a decreased release of IL-8 was triggered in the co-culture. Among these, treatment with sarilumab alone resulted in the greatest reduction of IL-8. The co-culture also showed clearly increased OPN concentrations than the respective monocultures, with OPN secretion apparently triggered by the OLCs. Particle exposure demonstrated decreased osteogenic differentiation using different treatment strategies. However, sarilumab administration caused a trend toward a decrease in IL-8 production after stimulation with IL-6 + sIL-6R. The blockade of IL-6 and its pathway have no significant effect on the osteogenic and osteoclastic differentiation of bone cells derived from patients with RA. Nonetheless, observed effects on the reduced IL-8 secretion need further investigation. [ABSTRACT FROM AUTHOR]

Primary stability is crucial for implant osseointegration and the long-term stability of cementless total joint replacements. Biomechanical studies have shown the potential of femoral stems for total knee replacements to reduce micromotions at the bone-implant interface. However, approaches such as focusing on the structural elasticity of the femoral stems are rarely described. Three groups with different femoral stem designs were investigated: group 1: flexible surface stem, group 2: flexible surface stem with open-porous structured lamellas, and group 3: solid stem (reference). The stems were implanted into bone substitute material and dynamically loaded for 1000 cycles. Relative movement and subsidence were measured optically, and axial pull-out forces were determined after dynamic testing. Relative movements increased to 0.10 mm (groups 1 and 2) compared to 0.03 mm (group 3). Subsidence increased to 0.08 mm (group 1) and 0.11 mm (group 2) compared to 0.06 mm (group 3). For each group, subsidence mainly occurred during the first 500 cycles. A similar convergence was observed in the further course. Pull-out forces increased to 1815.0 N (group 1) and 1347.1 N (group 2) compared to 1306.4 N (group 3). The flexible surface stem design resulted in higher relative movements and subsidence, but also exhibited increased pull-out forces. The relative movements were below the critical limit of 0.15 mm and represent a superposition of the elastic deformations of the interacting implant components as well as the micromotion at the bone-implant interface. Therefore, the novel flexible surface stem design appears to offer promising primary implant fixation. Graphical abstract [ABSTRACT FROM AUTHOR]

The requirements for bone substitute materials are multifaceted. Beside biomechanical stability, these materials should provide osteoconductive and osteoinductive properties to promote integration into the host tissue. So far, autologous bone is the only material, which combines all properties, but is naturally limited. Allogenic bone grafts have to be decellularized prior to implantation. This causes the reduction of biomechanical properties and the loss of osteoinductive qualities. High hydrostatic pressure (HHP) offers a gentle alternative for processing and supply of allogenic bone substitute materials while preserving biomechanical integrity. To determine whether osteogenic properties are retained by HHP treatment, mesenchymal stem cells (MSCs) were cultured with HHP‐treated and untreated allogenic trabecular bone blocks up to 28 days. Both, gene expression and protein analysis showed that HHP‐treated bone positively influenced differentiation of MSCs into osteoblasts and mineralization of bone matrix. This effect was greater in samples cultivated with HHP‐treated bone blocks. The present study shows that HHP treatment does not result in the reduction of osteoinductivity, thus serving as an alternative approach for processing allogeneic bone substitute materials. [ABSTRACT FROM AUTHOR]

For the in vitro examination of the effects on cells and tissues of metal ions derived from implants by wear and corrosion, a system is needed to release metal ions in a controlled and sustained manner. As small concentrations may have an impact on biological systems, a corresponding slow release over a defined period of time is necessary. Here, a manufacturing method of polymeric Poly(L-lactic acid) (PLLA) films with incorporated cobalt ions via dip coating is reported. The establishment of two analytical methods for the detection and quantification of cobalt ions is shown. High performance liquid chromatography enables cobalt quantification over a concentration range of 0.33 μg/mL up to 33 μg/mL in sample solutions. Extraction and detection of cobalt ions from solvent cast PLLA-cobalt-films shows the feasibility of the manufacturing method. Initial biocompatibility tests with manufactured PLLA-cobaltfilms showed no effects on adipose derived primary mesenchymal stem cells (adMSCs). [ABSTRACT FROM AUTHOR]

Due to advances in surgical procedures and the biocompatibility of materials used in total joint replacement, more and younger patients are undergoing these procedures. Although state-of-the-art joint replacements can last 20 years or longer, wear and corrosion is still a major risk for implant failure, and patients with these implants are exposed for longer to these corrosive products. It is therefore important to investigate the potential effects on the whole organism. Released nanoparticles and ions derived from commonly used metal implants consist, among others, of cobalt, nickel, and chromium. The effect of these metallic products in the process of osteolysis and aseptic implant loosening has already been studied; however, the systemic effect on other cell types, including neurons, remains elusive. To this end, we used human iPSC-derived motoneurons to investigate the effects of metal ions on human neurons. We treated human motoneurons with ion concentrations regularly found in patients, stained them with MitoSOX and propidium iodide, and analyzed them with fluorescence-assisted cell sorting (FACS). We found that upon treatment human motoneurons suffered from the formation of ROS and subsequently died. These effects were most prominent in motoneurons treated with 500 μM of cobalt or nickel, in which we observed significant cell death, whereas chromium showed fewer ROS and no apparent impairment of motoneurons. Our results show that the wear and corrosive products of metal implants at concentrations readily available in peri-implant tissues induced ROS and subsequently cell death in an iPSC-derived motoneuron cell model. We therefore conclude that monitoring of neuronal impairment is important in patients undergoing total joint replacement. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the mechanisms of the human body dynamics during the golf swing through a musculoskeletal simulation for different types of subjects to better understand the biomechanical aspects of the golf sport. Methods: The lower extremity model of the AnyBodyTM modeling system was adapted to an advanced knee model to capture the large knee axial rotations during golf swing using an inverse dynamic musculoskeletal approach. Swings performed by three golfers, one with apparent osteoarthritis in both knee joints, one with bilateral total knee arthroplasty and one healthy, were captured in a motion capture laboratory and simulated. Results: The golf swing generated a high axial rotation in the knee joint (approximately 25-31°). Ball impact represented the most critical time event, near which maximum loading of the lower extremity was observed, e.g., knee compression force raised to a maximum of 329% body weight. The fast rate of knee loading by large compression forces prior to ball impact was identified as a potential cause of knee injury in golfers. Conclusions: Our findings are comparable with previous experimental and computational studies, and the proposed musculoskeletal model can be employed to provide valuable information to clinicians and scientists, e.g., on the biomechanics of the lower extremities after total knee arthroplasty during golf swing. [ABSTRACT FROM AUTHOR]

The role of patella height is discussed controversially in total knee arthroplasty (TKA). Therefore, this computational study aims to systematically analyze the biomechanical effect of different patella heights on patellofemoral (PF) forces and kinematics after cruciate‐retaining (CR) TKA. We implemented a CR bicondylar TKA with a dome patellar button in a validated dynamic musculoskeletal multibody model of a male human knee joint. Retropatellar dynamics (contact force [N], shear force [N], patellar shift [mm], tilt [°], and rotation [°]) were evaluated during dual‐limb squat motion (flexion from 0° to 90°) with simulated active muscle forces and the effects of different patella heights (Blackburne‐Peel [BP] ratio of 0.39, 0.49, 0.65, 0.85, 1.01, and 1.1 were systematically examined). As active knee flexion increased, PF contact force also increased. Patella alta (BP = 1.1) resulted in higher PF contact forces compared to normal patella height (BP = 0.65) by up to 16%. Contrarily, patella baja was associated with decreased PF forces by 7%. Compared to patella baja (BP = 0.39), patella alta (BP = 1.1) considerably increased the contact force by up to 25%. Different patellar heights mainly affected PF shear forces during early knee flexion. Concerning PF kinematics, patella alta (BP = 1.1) yielded a greater lateral tilt of more than 4° and higher patellar rotation by up to 3° during deep knee flexion, compared to normal patella height (BP = 0.65). Our computational study indicates that patella alta is associated with the highest PF contact and shear force after the implantation of a CR bicondylar TKA. This should be considered in PF disorders following TKA. [ABSTRACT FROM AUTHOR]

Purpose: Zirconium dioxide ceramic has been successfully introduced as a framework material for fixed dental prostheses. To reduce manufacturing constraints, joining of subcomponents could be a promising approach to increase the mechanical performance of long‐span fixed dental prostheses. In this experimental study, the biomechanical behavior of monolithic and soldered framework specimens for fixed dental prostheses made of Y‐TZP was investigated. Materials and methods: Framework specimens (n = 80) of 5‐unit fixed dental prostheses made of Y‐TZP were prepared and divided into 10 equal groups. The specimens were monolithic or composed of subcomponents, which were joined using a silicate‐based glass solder. Thereby, three joint geometries (diagonal, vertical with an occlusal cap, and dental attachment‐based) were investigated. Moreover, the groups differed based on the mechanical test (static vs. dynamic) and further processing (veneered vs. unveneered). The framework specimens were cemented on alumina‐based jaw models, where the canine and second molar were acting as abutments before a point‐load was applied. In addition, µCT scans and microscopic fractography were used to evaluate the quality of soldered joints and to determine the causes of fracture. Results: The determined fracture loads of the different unveneered framework specimens in static testing did not vary significantly (p = 1). Adding a veneering layer significantly increased the mechanical strength for monolithic framework specimens from 1196.29 ± 203.79 N to 1606.85 ± 128.49 N (p = 0.008). In case of soldered specimens with a dental attachment‐based geometry, the mechanical strength increased from 1159.42 ± 85.65 N to 1249.53 ± 191.55 N (p = 1). Within the dynamic testing, no differences were observed between monolithic and soldered framework specimens. µCT scans and fractography proved that the dental attachment‐based joining geometry offers the highest quality. Conclusion: Using glass soldering technology, subcomponents of 5‐unit framework specimens made of Y‐TZP could be joined with mechanical properties comparable to those of monolithic frameworks. [ABSTRACT FROM AUTHOR]

Featured Application: Quasi-static finite element model to adjust the stiffness of 3D-printed insoles during walking for patients with diabetic foot by using ankle moments and joint reaction forces as efficient boundary conditions. Diabetes-adapted insoles are essential in prevention and rehabilitation of foot ulcers in diabetic foot syndrome. However, their manufacture is labour-intensive and costly. Therefore, the study aims to present an alternative method that allows the individual adjustment of the stiffness of the insoles using the finite element (FE) method and subsequent 3D printing. In the study, 3D gait analysis followed by musculoskeletal modelling was used to determine the boundary conditions of a healthy subject for the FE model. While muscle forces are elaborately implemented in most studies, this FE model presented a more efficient way by using ankle moments and joint reaction forces. The deviation between the simulated plantar peak pressure and the experimentally determined using the Pedar system amounted to 234 kPa in the heel area and 30 kPa in the toe area. The stiffness of the individual insole was adjusted by applying soft insole plugs in areas where high plantar pressures occurred during walking. Three different Young's moduli were analysed in these areas (0.5 MPa, 1.0 MPa, 1.5 MPa). The computer-based approach to adjust the stiffness of an individual insole revealed a plantar peak pressure reduction by 37% in the heel area and by 119% in the toe area with a Young's modulus of 0.5 MPa. The presented method could be a valuable tool in the cost-efficient development and engineering of subject-specific 3D-printed insoles for patients with diabetic foot syndrome. [ABSTRACT FROM AUTHOR]

Background: The rising number of total hip and knee arthroplasties and the decreasing availability of physiotherapists require clinically and economically effective rehabilitation approaches. Therefore, the present pilot study investigated the effect of a novel digital-assisted individualized group rehabilitation program on clinical and functional outcomes after total hip and knee arthroplasty. Methods: In this randomized controlled pilot study, 26 patients undergoing total knee or hip replacement were randomly assigned to either the intervention group (IG, novel digital-assisted group therapy) or the control group (CG, standard postoperative physiotherapy currently carried out in Germany). The IG received the novel digital-assisted group therapy twice per week for a six-months period, while the CG received individual outpatient therapy depending on the prescription of the supervising physician. The number of therapy sessions was recorded. Moreover, subjective outcomes (EuroQol-5Dimensions (EQ-5D) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)), functional outcome (30 s sit to stand test and timed up and go test (TUG)), as well as gait parameters were quantified preoperatively as well as at three and six months after surgery. Data were analyzed using an analysis of covariance with baseline-adjustment. Results: No patient-reported falls, pain, and hospital readmissions were recorded. On average, the IG received more therapy sessions. The clinical and functional outcomes were mainly not significantly different between groups at three- and six-months follow-up, but medium to large effect sizes for the differences in quality of life (EQ-5D) as well as pain, stiffness, and physical function (WOMAC), and TUG performance were observed in favor of the IG. However, the IG showed a higher variability of gait velocity after total joint replacement. Conclusion: The digital-assisted rehabilitation had positive effects on quality of life, pain, stiffness, physical function, and TUG performance. Nevertheless, the therapy concept may be improved by adding exercises focusing on gait performance to reduce gait variability. The results indicate that the digital-assisted therapy concept is effective and safe. Therefore, a consecutive full-scaled randomized controlled clinical trial is recommended. Trial registration: This study was retrospectively registered on 14/02/2022 in the German Clinical Trial Register (DRKS00027960). [ABSTRACT FROM AUTHOR]

(1) Background: Electrical stimulation is a promising alternative to promote bone fracture healing but with the limitation of tracking the osteogenesis progress in vivo. To overcome this issue, we present an opportunity to combine the electrical stimulation of a commercial titanium implant, which promotes osteogenesis within the fracture, with a real-time readout of the osteogenic progress by impedance sensing. This makes it possible to adjust the electrical stimulation modalities to the individual patient's fracture healing process. (2) Methods: In detail, osteogenic differentiation of several cell types was monitored under continuous or pulsatile electrical stimulation at 0.7 V AC/20 Hz for at least seven days on a titanium implant by electric cell-substrate impedance sensing (ECIS). For control, chemical induction of osteogenic differentiation was induced. (3) Results: The most significant challenge was to discriminate impedance changes caused by proliferation events from those initiated by osteogenic differentiation. This discrimination was achieved by remodeling the impedance parameter Alpha (α), which increases over time for pulsatile electrically stimulated stem cells. Boosted α-values were accompanied by an increased formation of actin stress fibers and a reduced expression of the focal adhesion kinase in the cell periphery; morphological alterations known to occur during osteogenesis. (4) Conclusions: This work provided the basis for developing an effective fracture therapy device, which can induce osteogenesis on the one hand, and would allow us to monitor the induction process on the other hand. [ABSTRACT FROM AUTHOR]

Aseptic implant loosening is the most common reason for revision surgery after total knee replacement. This is associated with adverse biological reactions to wear debris from the articulating implant components. To predict the amount of wear debris generated in situ, standard wear testing of total knee replacement (TKR) is carried out before its clinical use. However, wear data reported on retrievals of total knee replacement (TKR) revealed significant discrepancies compared with standard wear simulator studies. Therefore, the aim of the present study was to compare the wear patterns on identical posterior-cruciate-retaining TKR designs by analyzing retrieved and experimentally tested implants. The identification and classification of wear patterns were performed using 21 retrieved ultra-high-molecular-weight-polyethylene (UHMW-PE) inserts and four sets of inserts of identical design and material tested in a knee wear simulator. These four sets had undergone different worst-case conditions and a standard test in a wear simulator according to ISO 14243-1. Macroscopic and microscopic examinations of the polyethylene inserts were performed, including the determination of seven modes of wear that correspond to specific wear patterns, the calculation of wear areas, and the classification of the damage over the whole articulating area. Retrieved and standard wear simulator-tested UHMW-PE inserts showed significant differences in wear area and patterns. The total wear areas and the damage score were significantly larger on the retrievals (52.3% versus 23.9%, 32.7 versus 22.7). Furthermore, the range of wear patterns found on the retrievals was not reproducible in the simulator-tested inserts. However, good correspondence was found with the simulator-tested polyethylene inserts under worst-case conditions (third body wear), i.e., deep wear areas could be replicated according to the in vivo situation compared with other wear test scenarios. Based on the findings presented here, standard simulator testing can be used to directly compare different TKR designs but is limited in the prediction of their in situ wear. Preclinical wear testing may be adjusted by worst-case conditions to improve the prediction of in situ performance of total knee implants in the future. [ABSTRACT FROM AUTHOR]

Background: Perturbation-based balance training on a treadmill is an emerging method of gait stability training with a characteristic task nature that has had positive and sustained effects on balance recovery strategies and fall reduction. Little is known about the effects produced by shod and barefoot walking. We aimed to investigate which is more appropriate, shod or barefoot walking, for perturbation-based balance training in older adults.Methods: Fourteen healthy older adults (age: 68.29 ± 3.41 years; body height: 1.76 ± 0.10 m; body mass: 81.14 ± 14.52 kg) performed normal and trip-like perturbed walking trials, shod and barefoot, on a treadmill of the Gait Real-time Analysis Interactive Lab. The marker trajectories data were processed by Human Body Model software embedded in the Gait Offline Analysis Tool. The outcomes of stride length variability, stride time variability, step width variability, and swing time variability were computed and statistically analyzed by a two-way repeated-measures analysis of variance (ANOVA) based on gait pattern (normal gait versus perturbed recovery gait) and footwear condition (shod versus barefoot).Results: Footwear condition effect (p = 0.0310) and gait pattern by footwear condition interaction effect (p = 0.0055) were only observed in swing time variability. Gait pattern effects were detected in all four outcomes of gait variability.Conclusions: Swing time variability, independent of gait speed, could be a valid indicator to differentiate between footwear conditions. The lower swing time variability in perturbed recovery gait suggests that barefoot walking may be superior to shod walking for perturbation-based balance training in older adults. [ABSTRACT FROM AUTHOR]

Bone is a highly dynamic tissue characterized mainly by the interactions of osteoblasts and osteoclasts. When the healing ability of bone regeneration is disturbed, targeted biophysical stimulations such as electrical stimulation are applied. In this study the indirect effects of electrically stimulated human osteoblasts on osteoclastogenesis were investigated to better understand detailed cellular interactions. Therefore, two different cell developmental stages were examined: peripheral blood mononuclear cells (PBMCs) as precursors and pre-osteoclasts as differentiated cells. Previously, over a 21-day period, human osteoblasts were stimulated with a low-frequency alternating electric field. The supernatants were collected and used for an indirect co-culture of PBMCs and pre-osteoclasts. The cellular viability and the induction of differentiation and activity were analyzed. Further, the secretion of relevant osteoclastic markers was examined. Supernatants of 7 d and 14 d stimulated osteoblasts led to a decrease in the viability of PBMCs and an increased number of cells containing actin ring structures. Supernatants from osteoblasts stimulated over 7 d induced PBMC differentiation and pre-osteoclastic activation. Furthermore, pre-osteoclasts showed varying mRNA transcripts of MCP-1, ACP5, CA2, and CASP8 when cultivated with media from osteoblasts. Supernatants from day 21 did not influence PBMCs at all but increased the viability of pre-osteoclasts. We could show that different time points of stimulated osteoblasts have varying effects on the cells and that changes can be observed due to the differentiation stages of the cells. Through the effects of the indirect stimulation, it was possible to underline the importance of studying not only osteoblastic differentiation and mineralization behavior under electric stimulation but also analyzing changes in osteoclastogenesis and the activity of osteoclasts. [ABSTRACT FROM AUTHOR]

Biophysical stimulation by electric fields can promote bone formation in bone defects of critical size. Even though, long-term effects of alternating electric fields on the differentiation of osteoblasts are not fully understood. Human preosteoblasts were stimulated over 31 days to gain more information about these cellular processes. An alternating electric field with 0.7 Vrms and 20 Hz at two distances was applied and viability, mineralization, gene expression, and protein release of differentiation factors were analyzed. The viability was enhanced during the first days of stimulation. A higher electric field resulted in upregulation of typical osteogenic markers like osteoprotegerin, osteopontin, and interleukin-6, but no significant changes in mineralization. Upregulation of the osteogenic markers could be detected with a lower electric field after the first days of stimulation. As a significant increase in the mineralized matrix was identified, an enhanced osteogenesis due to low alternating electric fields can be assumed. [ABSTRACT FROM AUTHOR]

Background: The lower extremity may play a crucial role in compensating for gait perturbations. The study aimed to explore the mechanism of perturbation compensation by investigating the gait characteristics and lower extremity joint moment effects in young (YS) and older subjects (OS) during the first recovery gait following slipping (slipping_Rec1) and stumbling (stumbling_Rec1).Method: An automatic perturbation-triggered program was developed using D-Flow software based on the Gait Real-time Analysis Interactive Lab to induce the two aforementioned perturbations. Marker trajectories and ground reaction forces were recorded from 15 healthy YS (age: 26.53 ± 3.04 years; body height: 1.73 ± 0.07 m; body mass: 66.81 ± 11.44 kg) and 15 healthy OS (age: 68.33 ± 3.29 years; body height: 1.76 ± 0.10 m; body mass: 81.13 ± 13.99 kg). The Human Body Model was used to compute the variables of interest. One-way analysis of variance and independent samples t-test statistical analyses were performed.Results: In slipping_Rec1 and stumbling_Rec1, the change in gait pattern was mainly reflected in a significant increase in step width, no alterations in step length and stance/swing ratio were revealed. Based on perturbed task specificity, lower extremity joint moments increased or decreased at specific phases of the gait cycle in both YS and OS in slipping_Rec1 and stumbling_Rec1 compared to normal gait. The two perturbed gaits reflected the respective compensatory requirements for the lower extremity joints, with both sagittal and frontal joint moments producing compensatory effects. The aging effect was not reflected in the gait pattern, but rather in the hip extension moment during the initial stance of slipping_Rec1.Conclusions: Slipping appears to be more demanding for gait recovery than stumbling. Gait perturbation compensatory mechanisms for OS should concentrate on ankle strategy in the frontal plane and counter-rotation strategy around the hip. [ABSTRACT FROM AUTHOR]

Sequential cross-linked and annealed ultra-high-molecular-weight polyethylene (SX-PE) is known as a low-wear articulating partner, especially for total hip endoprostheses. Aging of polymeric materials, irrespective of if induced by shelf or in vivo life, can degrade their tribological and mechanical properties. However, changes in wear behavior of aged SX-PE liners have not been not quantified so far. An accelerated aging procedure, to simulate shelf and in vivo aging, was performed on thin SX-PE liners after five million load cycles using a simulator ("worn-aged") as well as on new SX-PE liners ("new-aged"). A subsequent hip simulator test was performed with both thin SX-PE liner sets in combination with large-diameter ceramic femoral head, representing a combination known as advantageous for treatment after revision because of dislocation. Oxidation indices were measured on the liners after each step of the procedure. SX-PE liners after accelerated aging show bedding-in phases during simulator test, which was a characteristic only known from clinical investigations. Hence, the wear rates of the "new-aged" ((1.71 ± 0.49) mg/million cycles) and of the "worn-aged" ((9.32 ± 0.09) mg/million cycles) SX-PE were increased in the first period compared to new unaged SX-PE liners. Subsequently, the wear rates decreased for "new-aged" and "worn-aged" inserts to (0.44 ± 0.48) mg/million cycles and (2.72 ± 0.05) mg/million cycles, respectively. In conclusion, the results show promising effects of accelerated aging on SX-PE liners in simulator testing and for potential long-term use in clinical applications. [ABSTRACT FROM AUTHOR]

Metallic deposition is a commonly observed phenomenon on the surface of revised femoral heads in total hip arthroplasty and can lead to increased wear due to third bodies. In order to find out the origin and composition of the transfer material, 98 retrieved femoral heads of different materials were examined with regard to the cause of revision, localization, pattern and composition of the transfer material by energy dispersive X-ray spectroscopy. We found that in 53.1%, the deposition was mostly in the region of the equator and the adjacent pole of the femoral heads. The most common cause for revision of heads with metallic deposition was polyethylene wear (43.9%). Random stripes (44.9%), random patches (41.8%) and solid patches (35.7%) were most prevalent on retrieved femoral heads. Random patches were a typical pattern in ceramic-on-ceramic bearing couples. The solid patch frequently occurred in association with dislocation of the femoral head (55%). The elemental analysis of the depositions showed a variety of different materials. In most cases, titanium was an element of the transferred material (76.5%). In addition to metallic components, several non-metallic components were also detected, such as carbon (49%) or sulfur (4.1%). Many of the determined elements could be assigned with regard to their origin with the help of the associated revision cause. Since the depositions lead to an introduction of third-body particles and thus to increased wear, the depositions on the bearing surfaces should be avoided in any case. [ABSTRACT FROM AUTHOR]

Interleukin (IL-) 6 is a key factor in the inflammatory processes of rheumatoid arthritis. Several biologic agents target the IL-6 signaling pathway, including sarilumab, a monoclonal antibody that blocks the IL-6 receptor and inhibits IL-6-mediated cis- and trans-signaling. A careful analysis of the IL-6 signaling blockade should consider not only inflammatory processes but also the regenerative functions of IL-6. The purpose of this study was to investigate whether inhibition of the IL-6 receptors affects differentiation of human primary osteoblasts (hOB). The effects of sarilumab on viability and the differentiation capacity in unstimulated osteoblasts as well as after stimulation with various IL-6 and sIL6-R concentrations were determined. Sarilumab treatment alone did not affect the differentiation or induction of inflammatory processes in hOB. However, the significant induction of alkaline phosphatase activity which was observed after exogenous IL-6/sIL-6R costimulation at the highest concentrations was reduced back to baseline levels by the addition of sarilumab. The IL-6 receptor blockade also decreased gene expression of mediators required for osteogenesis and bone matrix maintenance. Our results demonstrate that concomitant administration of the IL-6 receptor blocker sarilumab can inhibit IL-6/sIL-6R-induced osteogenic differentiation. [ABSTRACT FROM AUTHOR]

Skeletal muscle tissue engineering aims at generating biological substitutes that restore, maintain or improve normal muscle function; however, the quality of cells produced by current protocols remains insufficient. Here, we developed a multifactor-based protocol that combines adenovector (AdV)-mediated MYOD expression, small molecule inhibitor and growth factor treatment, and electrical pulse stimulation (EPS) to efficiently reprogram different types of human-derived multipotent stem cells into physiologically functional skeletal muscle cells (SMCs). The protocol was complemented through a novel in silico workflow that allows for in-depth estimation and potentially optimization of the quality of generated muscle tissue, based on the transcriptomes of transdifferentiated cells. We additionally patch-clamped phenotypic SMCs to associate their bioelectrical characteristics with their transcriptome reprogramming. Overall, we set up a comprehensive and dynamic approach at the nexus of viral vector-based technology, bioinformatics, and electrophysiology that facilitates production of high-quality skeletal muscle cells and can guide iterative cycles to improve myo-differentiation protocols. [ABSTRACT FROM AUTHOR]

Hydrogels have become an increasingly interesting topic in numerous fields of application. In addition to their use as immobilization matrixes in (bio)catalysis, they are widely used in the medical sector, e.g., in drug delivery systems, contact lenses, biosensors, electrodes, and tissue engineering. Cartilage tissue engineering hydrogels from natural origins, such as collagen, hyaluronic acid, and gelatin, are widely known for their good biocompatibility. However, they often lack stability, reproducibility, and mechanical strength. Synthetic hydrogels, on the other hand, can have the advantage of tunable swelling and mechanical properties, as well as good reproducibility and lower costs. In this study, we investigated the swelling and mechanical properties of synthetic polyelectrolyte hydrogels. The resulting characteristics such as swelling degree, stiffness, stress, as well as stress-relaxation and cyclic loading behavior, were compared to a commercially available biomaterial, the ChondroFiller® liquid, which is already used to treat articular cartilage lesions. Worth mentioning are the observed good reproducibility and high mechanical strength of the synthetic hydrogels. We managed to synthesize hydrogels with a wide range of compressive moduli from 2.5 ± 0.1 to 1708.7 ± 67.7 kPa, which addresses the span of human articular cartilage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bone morphogenic protein (BMP-) 2 plays an important role in the regeneration of bone defects by promoting osteogenic differentiation. However, several animal studies have reported adverse side effects of BMP-2, including osteoclast activation, induction of peroxisome proliferator- activated receptor gamma (PPARG)expression, and inflammation. High BMP-2 concentrations are thought to be responsible for these side effects. For this reason, primary pre-osteoblasts were exposed to lower BMP-2 concentrations (1 and 2 µg/mL). Long-term exposure (up to 28 days) was performed to investigate whether this stimulation protocol may promote osteogenic differentiation without causing the side effects mentioned above. The results showed that BMP-2 treatment for 14 or 28 days resulted in increased osteogenesis, through an increase in runt-related transcription factor 2, osterix, alkaline phosphatase, and integrin-binding sialoprotein expression. However, an increase in tumor necrosis factor alpha and receptor activator of nuclear factor kappa-Β ligand protein levels was observed after BMP-2 exposure, indicating also an increased potential for osteoclast activation by osteoblasts. Additionally, morphological changes like intracellular, filled vacuoles could be detected. Enhanced PPARG and perilipin 1 mRNA transcripts and lipid droplets indicated an induced adipogenic differentiation. Overall, the data demonstrate that long-term BMP-2 exposure promotes not only osteogenic differentiation but also adipogenesis and regulates mediators involved in osteoclast activation in vitro. [ABSTRACT FROM AUTHOR]

The in vitro generation of human cardiomyocytes derived from induced pluripotent stem cells (iPSC) is of great importance for cardiac disease modeling, drug-testing applications and for regenerative medicine. Despite the development of various cultivation strategies, a sufficiently high degree of maturation is still a decisive limiting factor for the successful application of these cardiac cells. The maturation process includes, among others, the proper formation of sarcomere structures, mediating the contraction of cardiomyocytes. To precisely monitor the maturation of the contractile machinery, we have established an imaging-based strategy that allows quantitative evaluation of important parameters, defining the quality of the sarcomere network. iPSC-derived cardiomyocytes were subjected to different culture conditions to improve sarcomere formation, including prolonged cultivation time and micro patterned surfaces. Fluorescent images of α-actinin were acquired using super-resolution microscopy. Subsequently, we determined cell morphology, sarcomere density, filament alignment, z-Disc thickness and sarcomere length of iPSC-derived cardiomyocytes. Cells from adult and neonatal heart tissue served as control. Our image analysis revealed a profound effect on sarcomere content and filament orientation when iPSC-derived cardiomyocytes were cultured on structured, line-shaped surfaces. Similarly, prolonged cultivation time had a beneficial effect on the structural maturation, leading to a more adult-like phenotype. Automatic evaluation of the sarcomere filaments by machine learning validated our data. Moreover, we successfully transferred this approach to skeletal muscle cells, showing an improved sarcomere formation cells over different differentiation periods. Overall, our image-based workflow can be used as a straight-forward tool to quantitatively estimate the structural maturation of contractile cells. As such, it can support the establishment of novel differentiation protocols to enhance sarcomere formation and maturity. [ABSTRACT FROM AUTHOR]

Nowadays, several configurations of total knee arthroplasty (TKA) implants are commercially available whose designs resulted from clinical and biomechanical considerations. Previous research activities led to the development of the so-called medial-pivot (MP) design. However, the actual benefits of the MP, with respect to other prosthesis designs, are still not well understood. The present work compares the impact of two insert geometries, namely the ultra-congruent (UC) and medial-pivot (MP), on the biomechanical behaviour of a bicondylar total knee endoprosthesis. For this purpose, a multibody model of a lower limb was created alternatively integrating the two implants having the insert geometry discretized. Joint dynamics and contact pressure distributions were evaluated by simulating a squat motion. Results showed a similar tibial internal rotation range of about 3.5°, but an early rotation occurs for the MP design. Furthermore, the discretization of the insert geometry allowed to efficiently derive the contact pressure distributions, directly within the multibody simulation framework, reporting peak pressure values of 33 MPa and 20 MPa for the UC and MP, respectively. Clinically, the presented findings confirm the possibility, through a MP design, to achieve a more natural joint kinematics, consequently improving the post-operative patient satisfaction and potentially reducing the occurrence of phenomena leading to the insert loosening. [ABSTRACT FROM AUTHOR]

The purpose of this computational study was to analyze the effects of different mobile-bearing (MB) total knee replacement (TKR) designs on knee joint biomechanics. A validated musculoskeletal model of the lower right extremity implanted with a cruciate-retaining fixed-bearing TKR undergoing a squat motion was adapted for three different MB TKR design variants: (I) a commercially available TKR design allowing for tibial insert rotation about the tibial tray with end stops to limit the range of rotation, (II) the same design without end stops, and (III) a multidirectional design with an additional translational degree-of-freedom (DoF) and end stops. When modeling the MB interface, two modeling strategies of different joint topologies were deployed: (1) a six DoF joint as a baseline and (2) a combined revolute-prismatic joint (two DoF joint) with end stops in both DoF. Altered knee joint kinematics for the three MB design variants were observed. The commercially available TKR design variant I yielded a deviation in internal-external rotation of the tibial insert relative to the tray up to 5° during knee flexion. Compared to the multidirectional design variant III, the other two variants revealed less femoral anterior-posterior translation by as much as 5 mm. Concerning the modeling strategies, the two DoF joint showed less computation time by 68%, 80%, and 82% for design variants I, II, and III, respectively. However, only slight differences in the knee joint kinematics of the two modeling strategies were recorded. In conclusion, knee joint biomechanics during a squat motion differed for each of the simulated MB design variants. Specific implant design elements, such as the presence of end stops, can impact the postoperative range of knee motion with regard to modeling strategy, and the two DoF joint option tested accurately replicated the results for the simulated designs with a considerably lower computation time than the six DoF joint. The proposed musculoskeletal multibody simulation framework is capable of virtually characterizing the knee joint dynamics for different TKR designs. [ABSTRACT FROM AUTHOR]