Strains on the human femur after revision total knee arthroplasty: An in vitro study using digital image correlation.

Pain at the tip of the stem of a knee prosthesis (End-of-Stem Pain) is a common problem in revision total knee arthroplasty (TKA). It may be caused by a problematic interaction between stem and bone, but the exact biomechanical correlate is still unknown. On top of this, there is no biomechanical study investigating End-of-Stem Pain at the distal femur using human specimens. Aim of this study was to find out whether the implantation of a revision total knee implant leads to high femoral surface strains at the tip of the stem, which the authors expect to be the biomechanical correlate of End-of-Stem Pain. We implanted 16 rotating hinge knee implants into 16 fresh-frozen human femora using the hybrid fixation technique and comparing two reaming protocols. Afterwards, surface strains on these femora were measured under dynamic load in two different load scenarios (climbing stairs and chair rising) using digital image correlation (DIC) and fracture patterns after overcritical load were analysed. Peak surface strains were found at the tip of the stem in several measurements in both load scenarios. There were no significant differences between the two compared groups (different trial sizes) regarding surface strains and fracture patterns. We conclude that implantation of a long intramedullary stem in revision TKA can lead to high surface strains at the tip of the stem that may be the correlate of femoral End-of-Stem Pain. This finding might allow for a targeted development of future stem designs that can lead to lower surface strains and therefore might reduce End-of-Stem Pain. Digital Image Correlation proved valid for the measurement of surface strains and can be used in the future to test new stem designs in vitro.

Rheological characterization of artificial paenan compositions produced by Paenibacillus polymyxa DSM 365.

Microbial exopolysaccharides offer a sustainable alternative to petroleum-based rheological modifiers. Recent studies revealed that the heteroexopolysaccharide produced by Paenibacillus polymyxa is composed of three distinct biopolymers, referred to as paenan I, II and III. Using CRISPR-Cas9 mediated knock-out variants of glycosyltransferases, defined polysaccharide compositions were produced and rheologically characterized in detail. The high viscosity and gel-like character of the wildtype polymer is proposed to originate from the non-covalent interaction between a pyruvate residue of paenan I and the glucuronic acid found in the backbone of paenan III. Paenan II conveys thermostable properties to the exopolysaccharide mixture. In contrast to the wildtype polymer mixture, knock-out variants demonstrated significantly altered rheological behavior. Using the rheological characterization performed in this study, tailor-made paenan variants and mixtures can be generated to be utilized in a wide range of applications including thickening agents, coatings, or high-value biomedical materials.

CRISPR-Cas9 driven structural elucidation of the heteroexopolysaccharides from Paenibacillus polymyxa DSM 365.

Paenibacillus polymyxa is a Gram-positive soil bacterium known for producing a wide range of exopolysaccharides. However, due to the biopolymer's complexity, structural elucidation has so far been inconclusive. Combinatorial knock-outs of glycosyltransferases were generated in order to separate distinct polysaccharides produced by P. polymyxa. Using a complementary analytical approach consisting of carbohydrate fingerprints, sequence analysis, methylation analysis as well as NMR spectroscopy, the structure of the repeating units of two additional heteroexopolysaccharides termed paenan I and paenan III were elucidated. Results for paenan I identified a trisaccharide backbone consisting of 1➔4-ß-d-Glc, 1➔4-ß-d-Man and a 1,3,4-branching ß-d-Gal residue with a sidechain comprising of a terminal ß-d-Gal3,4-Pyr and 1➔3-ß-d-Glc. For paenan III, results indicated a backbone consisting of 1➔3-ß-d-Glc, 1,3,4-linked α-d-Man and 1,3,4-linked α-d-GlcA. NMR analysis indicated monomeric ß-d-Glc and α-d-Man sidechains for the branching Man and GlcA residues respectively.

Biomechanical comparison of different rod-to-rod connectors to a conventional titanium- and cobalt chromium posterior spinal fixation system.

Introduction: Several types of rod-to-rod connectors are available for the extension of spinal fixation systems. However, scientific literature regarding the mechanical performance of different rod-to-rod connector systems is lacking. Research question: The goal of this study was to evaluate the mechanical characteristics of axial and lateral rod connectors in comparison to a conventional pedicle screw rod (titanium and cobalt chromium) construct. Material and method: Six types of instrumentations were investigated in a standardized test model to quantify the mechanical differences: 1: titanium rod; 2: titanium rod with axial connector; 3: titanium rod with lateral connector; 4: cobalt chromium rod; 5: cobalt chromium rod with axial connector; 6: cobalt chromium rod with lateral connector. All groups were tested in static compression, static torsion and dynamic compression and statistically compared regarding failure load and stiffness. Results: In static compression loading, the use of connectors increased the construct stiffness, but unaffected the yield load. The use of a cobalt chromium rod significantly increased by approximately 40% the yield load and stiffness in comparison to the titanium rod configurations. Under dynamic compression, a similar or higher fatigue strength for all tested groups in comparison to the titanium rod configuration was evaluated, with the exception of titanium rod with axial connector. Conclusion: Biomechanically, using rod connectors is a secure way for the extension of a construct and is mechanically equal to a conventional screw rod construct. However, in clinical use, attention should be paid regarding placement of the connectors at high loaded areas.

Computer-based analysis of different component positions and insert thicknesses on tibio-femoral and patello-femoral joint dynamics after cruciate-retaining total knee replacement.

BACKGROUND: Positioning of the implant components and tibial insert thickness constitute critical aspects of total knee replacement (TKR) that influence the postoperative knee joint dynamics. This study aimed to investigate the impact of implant component positioning (anterior-posterior and medio-lateral shift) and varying tibial insert thickness on the tibio-femoral (TF) and patello-femoral (PF) joint kinematics and contact forces after cruciate-retaining (CR)-TKR. METHOD: A validated musculoskeletal multibody simulation (MMBS) model with a fixed-bearing CR-TKR during a squat motion up to 90° knee flexion was deployed to calculate PF and TF joint dynamics for varied implant component positions and tibial insert thicknesses. Evaluation was performed consecutively by comparing the respective knee joint parameters (e.g. contact force, quadriceps muscle force, joint kinematics) to a reference implant position. RESULTS: The PF contact forces were mostly affected by the anterior-posterior as well as medio-lateral positioning of the femoral component (by 3 mm anterior up to 31 % and by 6 mm lateral up to 14 %). TF contact forces were considerably altered by tibial insert thickness (24 % in case of + 4 mm increase) and by the anterior-posterior position of the femoral component (by 3 mm posterior up to 16 %). Concerning PF kinematics, a medialised femoral component by 6 mm increased the lateral patellar tilt by more than 5°. CONCLUSIONS: Our results indicate that regarding PF kinematics and contact forces the positioning of the femoral component was more critical than the tibial component. The positioning of the femoral component in anterior-posterior direction on and PF contact force was evident. Orthopaedic surgeons should strictly monitor the anterior-posterior as well as the medio-lateral position of the femoral component and the insert thickness.

Biomechanical Effects of Stemmed Total Knee Arthroplasty on the Human Femur: A CT-Data Based Study.

End-of-stem pain of the femur is a common problem in revision total knee arthroplasty (TKA). It may be caused by a problematic interaction between stem and bone, but the exact biomechanical correlate is still unknown. The aim of this prospective study was to find out how the stem is positioned in the medullary canal, how the femoral geometry changes due to implantation, and whether the results are influenced by the diameter of the trial. We implanted 16 rotating hinge knee implants into 16 fresh-frozen human femora using the hybrid fixation technique and comparing two reaming protocols. We created 3-dimensional models of the specimens before and after implantation using CT-scans and calculated the differences. The main contact between stem and bone was found at the proximal 30 mm of the stem, especially anterior. We observed two different contact patterns of stem and bone. The cortical thickness was reduced especially at the anterior tip of the stem with a maximum reduction of 1405 ± 501 µm in the standard group and 980 ± 447 µm in the small_trial group, which is a relative reduction of 34 ± 14% (standard group) and 26 ± 14% (small_trial group). The bone experienced a deformation to posterior and lateral. We conclude that the tip of the stem is an important biomechanical region. Different contact patterns between stem and bone as well as the reduction in cortical thickness at the tip of the stem may play a role in the development of end-of-stem pain.

Endurance Behavior of Cemented Tibial Tray Fixation Under Anterior Shear and Internal-External Torsional Shear Testing: A New Methodological Approach.

BACKGROUND: Early total knee arthroplasty failures continue to surface in the literature. Cementation technique and implant design are two of the most important scenarios that can affect implant survivorship. Our objectives were to develop a more suitable preclinical test to evaluate the endurance of the implant-cement-bone interface under anterior shear and internal-external (I/E) torsional shear testing condition in a biomechanical sawbones. METHODS: Implants tested included the AS VEGA System PS and the AS Columbus CR/PS (Aesculap AG, Germany), with zirconium nitride (ZrN) coating. Tibial implants were evaluated under anterior shear and I/E torsional shear conditions with 6 samples in 4 test groups. For the evaluation of the I/E torsional shear endurance behavior, a test setup was created allowing for clinically relevant I/E rotation with simultaneous high axial/tibio-femoral load. The test was performed with an I/E displacement of ±17.2°, for 1 million cycles with an axial preload of 3,000 N. RESULTS: After the anterior shear test an implant-cement-bone fixation strength for the AS VEGA System tibial tray of 2,674 ± 754 N and for the AS Columbus CR/PS tibial tray of 2,177 ± 429 N was determined (P = .191). After I/E rotational shear testing an implant-cement-bone fixation strength for the AS VEGA System PS tray of 2,561 ± 519 N and for the AS Columbus CR/PS tray of 2,824 ± 515 N was resulted (P = .39). CONCLUSION: Both methods had varying degrees of failure modes from debonding to failure of the sawbones foam. These two intense biomechanical loading tests are more strenuous and more representative of clinical activity.

Structural elucidation of the fucose containing polysaccharide of Paenibacillus polymyxa DSM 365.

Paenibacillus polymyxa is an avid producer of exopolysaccharides of industrial interest. However, due to the complexity of the polymer composition, structural elucidation of the polysaccharide remained unfeasible for a long time. By using a CRISPR-Cas9 mediated knock-out strategy, all single glycosyltransferases as well as the Wzy polymerases were individually deleted in the corresponding gene cluster for the first time. Thereby, it was observed that the main polymer fraction was completely suppressed (or deleted) and a pure minor fucose containing polysaccharide could be isolated, which was named paenan II. Applying this combinatorial approach, the monosaccharide composition, sequence and linkage pattern of this novel polymer was determined via HPLC-MS, GC-MS and NMR. Furthermore, we demonstrated that the knock-out of the glycosyltransferases PepQ, PepT, PepU and PepV as well as of the Wzy polymerase PepG led to the absence of paenan II, attributing those enzymes to the assembly of the repeating unit.

The effect of cement augmentation on pedicle screw fixation under various load cases : results from a combined experimental, micro-CT, and micro-finite element analysis.

AIMS: Anchorage of pedicle screw rod instrumentation in the elderly spine with poor bone quality remains challenging. Our study aims to evaluate how the screw bone anchorage is affected by screw design, bone quality, loading conditions, and cementing techniques. METHODS: Micro-finite element (µFE) models were created from micro-CT (µCT) scans of vertebrae implanted with two types of pedicle screws (L: Ennovate and R: S4). Simulations were conducted for a 10 mm radius region of interest (ROI) around each screw and for a full vertebra (FV) where different cementing scenarios were simulated around the screw tips. Stiffness was calculated in pull-out and anterior bending loads. RESULTS: Experimental pull-out strengths were excellently correlated to the µFE pull-out stiffness of the ROI (R2 > 0.87) and FV (R2 > 0.84) models. No significant difference due to screw design was observed. Cement augmentation increased pull-out stiffness by up to 94% and 48% for L and R screws, respectively, but only increased bending stiffness by up to 6.9% and 1.5%, respectively. Cementing involving only one screw tip resulted in lower stiffness increases in all tested screw designs and loading cases. The stiffening effect of cement augmentation on pull-out and bending stiffness was strongly and negatively correlated to local bone density around the screw (correlation coefficient (R) = -0.95). CONCLUSION: This combined experimental, µCT and µFE study showed that regional analyses may be sufficient to predict fixation strength in pull-out and that full analyses could show that cement augmentation around pedicle screws increased fixation stiffness in both pull-out and bending, especially for low-density bone. Cite this article: Bone Joint Res 2021;10(12):797-806.

Influence of radiation conditions on the wear behaviour of Vitamin E treated UHMWPE gliding components for total knee arthroplasty after extended artificial aging and simulated daily patient activities.

The long term performance of total knee arthroplasty (TKA) with regards to the bearing materials is related to the aging behaviour of these materials. The use of highly crosslinked materials in hip arthroplasty improved the clinical outcome. Nevertheless, the outcome for these materials compared to conventional UHMWPE (ultra-high molecular weight polyethylene) remains controversial in TKA and alternative bearing materials may be advantageous to improve its outcome in the second and third decade. The aim of this study is the evaluation of the influence of radiation conditions on the wear behaviour of Vitamin E blended UHMWPE gliding components for TKA by simulation of extended aging and high demanding daily patient activities. For a medium radiation dose (30 kGy), the influence of the irradiation type (E-beam or Gamma radiation) and the thermal conditions (room temperature (RT) or heated to 115 °C) are evaluated in comparison to non-irradiated material. Significant influences on the wear behaviour were found for the radiation source and temperature during irradiation. Furthermore, no relevant degradation of the tested materials was observed after extended artificial aging. There was a good correspondence between the wear pattern in this study and retrievals.

Recent advances of Cas12a applications in bacteria.

Clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genome engineering and related technologies have revolutionized biotechnology over the last decade by enhancing the efficiency of sophisticated biological systems. Cas12a (Cpf1) is an RNA-guided endonuclease associated to the CRISPR adaptive immune system found in many prokaryotes. Contrary to its more prominent counterpart Cas9, Cas12a recognizes A/T rich DNA sequences and is able to process its corresponding guide RNA directly, rendering it a versatile tool for multiplex genome editing efforts and other applications in biotechnology. While Cas12a has been extensively used in eukaryotic cell systems, microbial applications are still limited. In this review, we highlight the mechanistic and functional differences between Cas12a and Cas9 and focus on recent advances of applications using Cas12a in bacterial hosts. Furthermore, we discuss advantages as well as current challenges and give a future outlook for this promising alternative CRISPR-Cas system for bacterial genome editing and beyond. KEY POINTS: • Cas12a is a powerful tool for genome engineering and transcriptional perturbation • Cas12a causes less toxic side effects in bacteria than Cas9 • Self-processing of crRNA arrays facilitates multiplexing approaches.

Patient-Specific Finite Element Models of Posterior Pedicle Screw Fixation: Effect of Screw's Size and Geometry.

Pedicle screw fixation is extensively performed to treat spine injuries or diseases and it is common for thoracolumbar fractures. Post-operative complications may arise from this surgery leading to back pain or revisions. Finite element (FE) models could be used to predict the outcomes of surgeries but should be verified when both simplified and realistic designs of screws are used. The aim of this study was to generate patient-specific Computed Tomography (CT)-based FE models of human vertebrae with two pedicle screws, verify the models, and use them to evaluate the effect of the screws' size and geometry on the mechanical properties of the screws-vertebra structure. FE models of the lumbar vertebra implanted with two pedicle screws were created from anonymized CT-scans of three patients. Compressive loads were applied to the head of the screws. The mesh size was optimized for realistic and simplified geometry of the screws with a mesh refinement study. Finally, the optimal mesh size was used to evaluate the sensitivity of the model to changes in screw's size (diameter and length) and geometry (realistic or simplified). For both simplified and realistic models, element sizes of 0.6 mm in the screw and 1.0 mm in the bone allowed to obtain relative differences of approximately 5% or lower. Changes in screw's length resulted in 4-10% differences in maximum deflection, 1-6% differences in peak stress in the screws, 10-22% differences in mean strain in the bone around the screw; changes in screw's diameter resulted in 28-36% differences in maximum deflection, 6-27% differences in peak stress in the screws, and 30-47% differences in mean strain in the bone around the screw. The maximum deflection predicted with realistic or simplified screws correlated very well (R 2 = 0.99). The peak stress in screws with realistic or simplified design correlated well (R 2 = 0.82) but simplified models underestimated the peak stress. In conclusion, the results showed that the diameter of the screw has a major role on the mechanics of the screw-vertebral structure for each patient. Simplified screws can be used to estimate the mechanical properties of the implanted vertebrae, but the systematic underestimation of the peak stress should be considered when interpreting the results from the FE analyses.

Correlation between different instrumentation variants and the degree of destabilization in treating cervical spondylotic spinal canal stenosis by unilateral hemilaminectomy with bilateral decompression: a biomechanical investigation.

PURPOSE: Unilateral hemilaminectomy with bilateral decompression (BDZ) was proposed as an alternative decompressive procedure in cervical spondylotic myelopathy (CSM). Despite promising clinical results, the destabilizing effect is yet unknown. We therefore performed a biomechanical study to investigate whether lateral mass screw fixation should follow BDZ. METHODS: Six human C2-C7 cervical specimens were tested under various conditions: native, unilateral hemilaminectomy with bilateral decompression without/with fixation (BDZ/BDF), unilateral hemilaminectomy with bilateral decompression and unilateral foraminotomy without/with fixation (UFZ/UFF), unilateral hemilaminectomy with bilateral decompression and bilateral foraminotomy without/with fixation (BFZ/BFF), and laminectomy without/with fixation (LAZ/LAF). Instrumention was applied from C3-C6. For each condition, the three-dimensional kinematics of the cervical specimen were measured in three main loading directions with an ultrasonic motion analysis system. ANOVA was used to determine differences between the specific segment conditions to assess the parameter's range of motion (ROM) and neutral zone (NZ). RESULTS: For flexion-extension, lateral bending and axial rotation, ROM of BDZ, UFZ, BFZ and LAZ remained at the level of the native condition (p > 0.74), whereas fixation reduced ROM significantly (p < 0.01). Between BDF, UFF, BFF and LAF, no significant differences in reduction in ROM were seen (p > 0.49). Results for NZ were equivalent to ROM in flexion-extension and lateral bending. For axial rotation, NZ remained almost constant on the native level for all tested conditions. CONCLUSION: Bilateral decompression via a hemilaminectomy, even if combined with foraminotomy, could be a less invasive treatment option for multilevel CSM in patients with lordotic cervical alignment and absence of segmental instability.

No effect in primary stability after increasing interference fit in cementless TKA tibial components.

Cementless total knee arthroplasty (TKA) implants rely on interference fit to achieve initial stability. However, the optimal interference fit is unknown. This study investigates the effect of using different interference fit on the initial stability of tibial TKA implants. Experiments were performed on human cadaveric tibias using a low interference fit of 350 µm of a clinically established cementless porous-coated tibial implant and a high interference fit of 700 µm. The Orthoload peak loads of gait and squat were applied to the specimens with a custom-made load applicator. Micromotions and gaps opening/closing were measured at the bone-implant interface using Digital Image Correlation (DIC) in 6 regions of interest (ROIs). Two multilevel linear mixed-effect models were created with micromotions and gaps as dependent variables. The results revealed no significant differences for micromotions between the two interference fits (gait p = 0.755, squat p = 0.232), nor for gaps opening/closing (gait p = 0.474, squat p = 0.269). In contrast, significant differences were found for the ROIs in the two dependent variables (p < 0.001), where more gap closing was seen in the posterior ROIs than in the anterior ROIs during both loading configurations. This study showed that increasing the interference fit from 350 to 700 µm did not influence initial stability.

The effect of different interference fits on the primary fixation of a cementless femoral component during experimental testing.

Cementless femoral total knee arthroplasty (TKA) components use a press-fit (referred to as interference fit) to achieve initial fixation. A higher interference fit could lead to a superior fixation, but it could also introduce more damage to the bone during implantation. The purpose of the current study was to investigate the effect of interference fit on the micromotions and gap opening/closing at the bone-implant interface. Experimental tests were performed in six pairs of cadaveric femurs implanted with femoral components using a low interference fit of 350 µm and a high interference fit of 700 µm. The specimens were subjected to the peak loads of gait and squat, based on the Orthoload dataset. Digital Image Correlation (DIC) was used to measure the micromotions and opening/closing in different regions of interest (ROIs). Two linear mixed-effect statistical models were created with micromotions and gap opening/closing as dependent variables. ROIs, loading conditions, and implant designs as independent variables, and cadaver specimens as random intercepts. The results revealed no significant difference between the two interference fit implants for micromotions (p = 0.837 for gait and p = 0.065 for squat), nor for the gap opening/closing (p = 0.748 for gait and p = 0.561 for squat). In contrast, significant differences were found between loading and most of the ROIs in both dependent variables (p < 0.0001). Additionally, no difference in bone deformation was found between low and high interference fit. Changing interference between either 350 µm or 700 µm did not affect the primary stability of a femoral TKA component. There could be an interference fit threshold beyond which fixation does not further improve.

Novel Prokaryotic CRISPR-Cas12a-Based Tool for Programmable Transcriptional Activation and Repression.

Transcriptional perturbation using inactivated CRISPR-nucleases (dCas) is a common method in eukaryotic organisms. While rare examples of dCas9-based tools for prokaryotes have been described, multiplexing approaches are limited due to the used effector nuclease. For the first time, a dCas12a derived tool for the targeted activation and repression of genes was developed. Therefore, a previously described SoxS activator domain was linked to dCas12a to enable the programmable activation of gene expression. A proof of principle of transcriptional regulation was demonstrated on the basis of fluorescence reporter assays using the alternative host organism Paenibacillus polymyxa as well as Escherichia coli. Single target and multiplex CRISPR interference targeting the exopolysaccharide biosynthesis of P. polymyxa was shown to emulate polymer compositions of gene knockouts. The simultaneous expression of 11 gRNAs targeting multiple lactate dehydrogenases and a butanediol dehydrogenase resulted in decreased lactate formation, as well as an increased butanediol production in microaerobic fermentation processes. Even though Cas12a is more restricted in terms of its genomic target sequences compared to Cas9, its ability to efficiently process its own guide RNAs in vivo makes it a promising tool to orchestrate sophisticated genetic reprogramming of bacterial cells or to screen for engineering targets in the genome. The developed tool will accelerate metabolic engineering efforts in the alternative host organism P. polymyxa and might be also applied for other bacterial cell factories.

Engineering of the 2,3-butanediol pathway of Paenibacillus polymyxa DSM 365.

Paenibacillus polymyxa is a Gram-positive, non-pathogenic soil bacterium that has been extensively investigated for the production of R-,R-2,3-butanediol in exceptionally high enantiomeric purity. Rational metabolic engineering efforts to increase productivity and product titers were restricted due to limited genetic accessibility of the organism up to now. By use of CRISPR-Cas9 mediated genome editing, six metabolic mutant variants were generated and compared in batch fermentations for the first time. Downstream processing was facilitated by completely eliminating exopolysaccharide formation through the combined knockout of the sacB gene and the clu1 region, encoding for the underlying enzymatic machinery of levan and paenan synthesis. Spore formation was inhibited by deletion of spoIIE, thereby disrupting the sporulation cascade of P. polymyxa. Optimization of the carbon flux towards 2,3-butanediol was achieved by deletion of the lactate dehydrogenase ldh1 and decoupling of the butanediol dehydrogenase from its natural regulation via constitutive episomal expression. The improved strain showed 45 % increased productivity, reaching a final concentration of 43.8 g L-1 butanediol. A yield of 0.43 g g-1 glucose was achieved, accounting for 86 % of the theoretical maximum.

Metabolic engineering for production of functional polysaccharides.

Functional carbohydrate polymers are of immense industrial interest for high value applications. Distinct biosynthetic pathways allow for metabolic engineering approaches for production in microbial cell factories. The most common strategies in recent years included the attenuation of central carbon metabolism, improved substrate utilization or enhanced intracellular sugar nucleotide precursor levels. Recombinant expression in more suitable surrogate host organisms has demonstrated remarkable results for the heterologous production of glycosaminoglycans. However, industrial application of pharmacological active functional polysaccharides is often limited by costly post-polymerization modifications and downstream processing. With increasing knowledge of bottleneck enzymes and fluxes, it will be possible to enable a sustainable microbial production of high value polysaccharides and tailor artificial polymers towards specific applications.

Musculoskeletal Multibody Simulation Analysis on the Impact of Patellar Component Design and Positioning on Joint Dynamics after Unconstrained Total Knee Arthroplasty.

Patellofemoral (PF) disorders are considered a major clinical complication after total knee replacement (TKR). Malpositioning and design of the patellar component impacts knee joint dynamics, implant fixation and wear propagation. However, only a limited number of studies have addressed the biomechanical impact of the patellar component on PF dynamics and their results have been discussed controversially. To address these issues, we implemented a musculoskeletal multibody simulation (MMBS) study for the systematical analysis of the patellar component's thickness and positioning on PF contact forces and kinematics during dynamic squat motion with virtually implanted unconstrained cruciate-retaining (CR)-TKR. The patellar button thickness clearly increased the contact forces in the PF joint (up to 27%). Similarly, the PF contact forces were affected by superior-inferior positioning (up to 16%) and mediolateral positioning (up to 8%) of the patellar button. PF kinematics was mostly affected by the mediolateral positioning and the thickness of the patellar component. A medialization of 3 mm caused a lateral patellar shift by up to 2.7 mm and lateral patellar tilt by up to 1.6°. However, deviations in the rotational positioning of the patellar button had minor effects on PF dynamics. Aiming at an optimal intraoperative patellar component alignment, the orthopedic surgeon should pay close attention to the patellar component thickness in combination with its mediolateral and superior-inferior positioning on the retropatellar surface. Our generated MMBS model provides systematic and reproducible insight into the effects of patellar component positioning and design on PF dynamics and has the potential to serve as a preoperative analysis tool.