Human Knee Research Articles

The common marmoset as a translational model of age-related osteoarthritis.

Age-related osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes in nearly every intra- and peri-articular tissue that contributes to disability in older adults. Studying the etiology of age-related OA in humans is difficult due to an unpredictable onset and insidious nature. A barrier in developing OA modifying therapies is the lack of translational models that replicate human joint anatomy and age-related OA progression. The purpose of this study was to determine whether the common marmoset is a faithful model of human age-related knee OA. Semi-quantitative microCTscoring revealed greater radiographic OA in geriatric versus adult marmosets, and the age-related increase in OA prevalence was similar between marmosets and humans. Quantitative assessments indicate greater medial tibial cortical and trabecular bone thickness and heterogeneity in geriatric versus adult marmosets which is consistent with an age-related increase in focal subchondral bone sclerosis. Additionally, marmosets displayed an age-associated increase in synovitis and calcification of the meniscus and patella. Histological OA pathology in the medial tibial plateau was greater in geriatric versus adult marmosets driven by articular cartilage damage, proteoglycan loss, and alteredchondrocyte cellularity. The age-associated increase in medial tibial cartilage OA pathology and meniscal calcification was greater in female versus male geriatric marmosets. Overall, marmosets largely replicate human OA as evident by similar 1) cartilage and skeletal morphology, 2) age-related progression in OA pathology, and 3) sex differences in OA pathology with increasing age. Collectively, these data suggest that the common marmoset is a highly translatable model ofthe naturally occurring, age-related OA seenin humans.

Valgus malalignment causes increased forces on a medial collateral ligament reconstruction under dynamic valgus loading: Abiomechanical study.

To investigate the forces on a medial collateral ligament (MCL) reconstruction (MCLR) relative to the valgus alignment of the knee. Eight fresh-frozen human cadaveric knees were subjected to dynamic valgus loading at 400 N using a custom-made kinematics rig. After resection of the superficial medial collateral ligament, a single-bundle MCLR with a hamstring tendon autograft was performed. A medial opening wedge distal femoral osteotomy was performed and fixed with an external fixator to gradually adjust the alignment in 5°increments from 0° to 10° valgus. For each degree of valgus deformity, the resulting forces acting on the MCLR were measured through a force sensor and captured in 15° increments from 0° to 60° of knee flexion. Irrespective of the degree of knee flexion, increasing valgus malalignment resulted in significantly increased forces acting on the MCLR compared to neutral alignment (p < 0.05). Dynamic loading at 5° valgus resulted in increased forces on the MCLR at all flexion angles ranging between 16.2 Nand 18.5 N (p < 0.05 from 0° to 30°; p < 0.01 from 45° to 60°). A 10° valgus malalignment further increased the forces on the MCLR at all flexion angles ranging between 29.4 Nand 40.0 N (p < 0.01 from 0° to 45°, p < 0.05 at 60°). Valgus malalignment of the knee caused increased forces acting on the reconstructed MCL. In cases of chronic medial instabilities accompanied by a valgus deformity ≥ 5°, a realigning osteotomy should be considered concomitantly to the MCLR to protect the graft and potentially reduce graft failures. Level III.

Robotic-assisted Total Knee Arthroplasty Technology Provides a Repeatable and Reproducible Method of Assessing Soft Tissue Balance.

Soft-tissue balancing is an important factor in primary total knee arthroplasty (TKA), with 30 to 50% of TKA revisions attributed to technical operative factors including soft-tissue balancing. Robotic-assisted TKA (RATKA) offers opportunities for improved soft-tissue balancing methods. This study aimed to evaluate the repeatability and reproducibility of ligamentous laxity assessments during RATKA using a digital tensioner.Three experienced RATKA surgeons assessed preresection and trialing phases of 12 human cadaveric knees with varying degrees of arthritis. Ligamentous laxity was assessed with manual varus and valgus stresses in extension and flexion, with a digital tensioner providing feedback on the change of laxity displacement. Intraclass correlation coefficient (ICC) analyses were used to determine the repeatability within a single surgeon and reproducibility between the three surgeons.The results showed excellent repeatability and reproducibility in ligamentous laxity assessment during RATKA. Surgeons had excellent repeatability for preresection and trialing assessments, with median ICC values representing excellent reproducibility between surgeons. Surgeons were repeatable within 1 or 1.5 mm for preresection and trialing assessments. On average, the variation within a surgeon was 0.33 ± 0.26 mm during preresection and 0.29 ± 0.28 mm during trialing. When comparing surgeons to each other, they were reproducible within an average of 0.69 ± 0.33 mm for preresection and 0.65 ± 0.31 mm for trialing.This study demonstrated the reliability of robotic-assisted soft-tissue balancing techniques, providing control over ligamentous laxity assessments, and potentially leading to better patient outcomes. The digital tensioner used in this study provided excellent repeatability and reproducibility in ligamentous laxity assessment during RATKA, highlighting the potential benefits of incorporating robotics in TKA procedures.

Voluntary activation of human knee extensors during isotonic shortening contractions.

The interpolated twitch technique (ITT) is often used to assess voluntary activation during isometric contractions; however, this may have limited relevance to dynamic contractions. Although the ITT has been applied to relatively slow isokinetic contractions (< 150°/s), it has received limited consideration during unconstrained velocity (i.e., isotonic) contractions, despite their relevance to natural movements. Here, we explored the ITT during isotonic knee extension contractions using a modified dynamometer. Young males (n = 6) and females (n = 4) performed isometric and isotonic knee extension contractions of sub-maximal and maximal intensities with doublet (150 Hz) muscle belly stimulations to assess voluntary activation. Following each voluntary isotonic contraction (velocity range ~ 35°/s to ~ 275°/s), resting potentiated doublets were evaluated during passive joint rotation at the same angular velocity achieved during voluntary efforts, to account for force-velocity characteristics. Correlations between voluntary activation and the proportion of maximal torque or power were evaluated for isometric and isotonic contractions, respectively. Isometric voluntary activation was strongly correlated with increasing torque output (r = 0.96, p < 0.001). Doublet torque during passive joint rotation displayed a hyperbolic relationship with increasing angular velocity (r = 0.98, p < 0.001). Isotonic voluntary activation was strongly correlated with increasing power output (r = 0.89, p < 0.001). During maximal effort contractions, no differences were observed in voluntary activation between isometric and isotonic conditions (89.4% vs. 89.2%, p = 0.904). The ITT is a valid approach to evaluate voluntary activation during an isotonic contraction using a modified dynamometer. Participants were able to achieve a similar high level of voluntary activation during isometric and isotonic contractions.

Influence of build orientation and support structure on additive manufacturing of human knee replacements: a computational study.

Developing patient-specific implants has an increasing interest in the application of emerging additive manufacturing (AM) technologies. On the other hand, despite advances in total knee replacement (TKR), studies suggest that up to 20% of patients with elective TKR are dissatisfied with the outcome. By creating 3D objects from digital models, AM enables the production of patient-specific implants with complex geometries, such as those required for knee replacements. Previous studies have highlighted concerns regarding the risk of residual stresses and shape distortions in AM parts, which could lead to structural failure or other complications. This article presents a computational framework that uses CT images to create patient-specific finite element models for optimizing AM knee replacements. The workflow includes image processing in the open-source software 3DSlicer and MeshLab and AM process simulations in the commercial platform 3DEXPERIENCE. The approach is demonstrated on a distal femur replacement for a 50-year-old male patient from the open-access Natural Knee Data. The results show that build orientations have a significant impact on both shape distortions and residual stresses. Support structures have a marginal effect on residual stresses but strongly influence shape distortions, whereas conical support exhibits a maximum distortion of 18.5 mm. Future research can explore how these factors affect the functionality of AM knee replacements under in-service loading.

Exposure of Hoffa Fractures Is Improved by Posterolateral and Posteromedial Extensile Approaches: A Qualitative and Quantitative Anatomical Study.

The current literature lacks recommendations regarding surgical approaches to best visualize and reduce Hoffa fractures. The aims of this study were to (1) define surgical corridors to the posterior portions of the lateral and medial femoral condyles and (2) compare the articular surface areas visible with different approaches. Eight fresh-frozen human cadaveric knees (6 male and 2 female donors; mean age, 68.2 ± 10.2 years) underwent dissection simulating 6 surgical approaches to the distal femur. The visible articular surface areas for each approach were marked using an electrocautery device and subsequently analyzed using image-processing software. The labeled areas of each femoral condyle were statistically compared. At 30° of flexion, visualization of the posterior portions of the lateral and medial femoral condyles was not possible by lateral and medial parapatellar approaches, as only the anterior 29.4% ± 2.1% of the lateral femoral condyle and 25.6% ± 2.8% of the medial condyle were exposed. Visualization of the lateral femoral condyle was limited by the posterolateral ligamentous structures, hence a posterolateral approach only exposed its central (13.1% ± 1.3%) and posterior (12.4% ± 1.1%) portions. Posterolateral extension by an osteotomy of the lateral femoral epicondyle significantly improved the exposure to 53.4% ± 2.7% and, when combined with a Gerdy's tubercle osteotomy, to 70.9% ± 4.1% (p < 0.001). For the posteromedial approach, an arthrotomy between the anteromedial retinaculum and the superficial medial collateral ligament, and one between the posterior oblique ligament and the medial gastrocnemius tendon, allowed visualization of the central (13.5% ± 2.2%) and the posterior (14.6% ± 2.3%) portions of the medial femoral condyle, while a medial femoral epicondyle osteotomy significantly improved visualization to 66.1% ± 5.5% (p < 0.001). Visualization of the posterior portions of the femoral condyles is limited by the specific anatomy of each surgical corridor. Extension by osteotomy of the femoral epicondyles and Gerdy's tubercle significantly improved articular surface exposure of the femoral condyles. Knowledge of the surgical approach-specific visualization of the articular surface of the femoral condyles might be helpful to properly reduce small Hoffa fragments.

Comparison of the Efficacy of Human Umbilical Cord-Derived and Bone Marrow Aspirate Concentrate Mesenchymal Stem Cells for Cartilage Repair Defects of the Knee via Arthroscopic Implementation on Scaffolds in a Retrospective Study.

Injuries to the articular cartilage of the human knee joint, commonly resulting from trauma, inflammation, or age- and activity-related wear and tear, have significant implications, primarily leading to osteoarthritis (OA). Conservative treatments for such injuries often yield suboptimal clinical outcomes. Surgical interventions using current methods may not consistently provide satisfactory results, largely due to the formation of low-quality scar tissue lacking the biomechanical properties of hyaline cartilage. In this retrospective study, we compared the results of two promising methods for regenerating cartilage defects in the knee joints using scaffolds soaked with stem cells of different origins: bone marrow aspirate concentrate mesenchymal stem cells (BMAC-MSCs) and human umbilical cord-derived mesenchymal stem cells (hUCB-MSCs). We evaluated 39 patients (39 knees, hUCB-MSCs: 20 knees, BMAC: 19 knees) at the 12-month follow-up using VAS, KOOS, Lysholm scales and radiologically with M-MOCART 2.0 score. The analysis demonstrated substantial overall improvement in both groups, notably reflected in enhanced quality of life for the patients. Interestingly, the final scores in the hUCB-MSCs group were comparable to those in the BMAC-MSCs group, with no statistically significant differences observed, despite variations in preoperative age and lesion size. Notably, the hUCB-MSCs group consisted of significantly older individuals with larger lesion sizes. Both procedures were found to be safe, and improvement was observed in both groups, which holds promise for future clinical investigations.

Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration

ObjectivesSingle-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations.MethodsSingle-cell RNA sequencing and spatially resolved transcriptomic technology have...

Design of lower limb rehabilitation exoskeleton with self-adaptive knee optimal force

With the increasingly serious trend of population aging in China, various diseases of the elderly are emerging in an endless stream, including hemiplegia, half limb disorder, limb numbness, hemianopia, and aphasia, with a high disability rate. The available auxiliary device cannot make a clear assistance for the patient, so that this design plans to make an exoskeleton for the patients who need effective rehabilitation alternatives and improve the rehabilitation efficiency. In this design, we would create Solid works model with some joint to fit human knees and then select sensors which are suitable to collect signs to depict kinematics features. The model, which has self-adaptation for receiving force signs from calf and knee joint, depends on the different force points of the calf lift affecting the stress state of the knee joint. Because the different stress points of the calf lift directly affect the stress state of the knee, so to find the best stress point of the calf is the research direction of this paper. In order to find the best and the most suitable force point of the human lower limb, we two methods, step-by-step process and dichotomy process, were discussed and compared in this study. Reasonable material may decide the robotic features.

Accuracy of photon-counting computed tomography for the measurement of bone quality in the knee

Visualization and quantification of bone microarchitecture in the human knee allows gaining insight into normal bone structure, and into the structural changes occurring in the onset and progression of bone diseases such as osteoporosis and osteoarthritis. However, current imaging modalities have limitations in capturing the intricacies of bone microarchitecture. Photon counting computed tomography (PCCT) is a promising imaging modality that presents high-resolution three-dimensional visualization of bone with a large field of view. However, the potential of PCCT in assessing trabecular microstructure has not been investigated yet. Therefore, this study aimed to evaluate the accuracy of PCCT in quantifying bone microstructure and bone mechanics in the knee. Five human cadaveric knees were scanned ex vivo using a PCCT scanner (Naetom alpha, Siemens, Germany) with an in-plane resolution of 146.5 μm and slice thickness of 100 μm. To assess accuracy, the specimens were also scanned with a high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT II, Scanco Medical, Switzerland) with a nominal isotropic voxel size of 60.7 μm as well as with micro-computed tomography (micro-CT; TESCAN UniTOM XL, Czech Republic) with a nominal isotropic voxel size of 25 μm which can be considered gold standards for in vivo and ex vivo scanning, respectively. The thickness and porosity of the subchondral bone and the microstructure of the underlying trabecular bone were assessed in the load bearing regions of the proximal tibia and distal femur. The apparent Young's modulus was determined by micro-finite element (μFE) analysis of subchondral trabecular bone (STB) in the load bearing regions of the proximal tibia using PCCT, HR-pQCT and micro-CT images. The correlation between PCCT measurements and micro-CT and HR-pQCT, respectively, was calculated. The coefficients of determination (R2) between PCCT and micro-CT based parameters, ranged from 0.69 to 0.87. The coefficients of determination between PCCT and HR-pQCT were slightly higher and ranged from 0.71 to 0.91. Apparent Young's modulus, assessed by μFE analysis of PCCT images, correlated well with that of micro-CT (R2 = 0.80, mean relative difference = 19 %). However, PCCT overestimated the apparent Young's modulus by 47 %, but the correlation (R2 = 0.84) remained strong when compared to HR-pQCT. The results of this study suggest that PCCT can be used to quantify bone microstructure in the knee.

Protective Effect of Knee Postoperative Fluid on Oxidative-Induced Damage in Human Knee Articular Chondrocytes.

The oxidative-stress-elicited deterioration of chondrocyte function is the initial stage of changes leading to the disruption of cartilage homeostasis. These changes entail a series of catabolic damages mediated by proinflammatory cytokines, MMPs, and aggrecanases, which increase ROS generation. Such uncontrolled ROS production, inadequately balanced by the cellular antioxidant capacity, eventually contributes to the development and progression of chondropathies. Several pieces of evidence show that different growth factors, single or combined, as well as anti-inflammatory cytokines and chemokines, can stimulate chondrogenesis and improve cartilage repair and regeneration. In this view, hypothesizing a potential growth-factor-associated action, we investigate the possible protective effect of post-operation knee fluid from patients undergoing prosthesis replacement surgery against ROS-induced damage on normal human knee articular chondrocytes (HKACs). To this end, HKACs were pre-treated with post-operation knee fluid and then exposed to H2O2 to mimic oxidative stress. Intracellular ROS levels were measured by using the molecular probe H2DCFDA; cytosolic and mitochondrial oxidative status were assessed by using HKACs infected with lentiviral particles harboring the redox-sensing green fluorescent protein (roGFP); and cell proliferation was determined by measuring the rate of DNA synthesis with BrdU incorporation. Moreover, superoxide dismutase (SOD), catalase, and glutathione levels from the cell lysates of treated cells were also measured. Postoperative peripheral blood sera from the same patients were used as controls. Our study shows that post-operation knee fluid can counteract H2O2-elicited oxidative stress by decreasing the intracellular ROS levels, preserving the cytosolic and mitochondrial redox status, maintaining the proliferation of oxidatively stressed HKACs, and upregulating chondrocyte antioxidant defense. Overall, our results support and propose an important effect of post-operation knee fluid substances in maintaining HKAC function by mediating cell antioxidative system upregulation and protecting cells from oxidative stress.

A modified anatomical posterior cruciate ligament reconstruction technique using the posterior septum and posterior capsule as landmarks to position the low tibial tunnel

BackgroundLowering the exit position of the tibial tunnel can improve the clinical efficacy of posterior cruciate ligament (PCL) reconstruction, however, there is no unified positioning standard. This study aimed to use novel soft tissue landmarks to create a low tunnel.MethodsA total of 14 human cadaveric knees and 12 patients with PCL injury were included in this study. Firstly, we observed the anatomical position between the PCL, posterior septum, and other tissue, and evaluated the relationship between the center of the low tibial tunnel (SP tunnel) and posterior septum and distal reflection of posterior capsule, and using computed tomography (CT) to evaluate distance between the center of the SP tunnel with bony landmarks. Then, evaluated the blood vessels content in the posterior septum with HE staining. Finally, observed the posterior septum and distal reflection of the posterior capsule under arthroscopy to explore the clinical feasibility of creating a low tibial tunnel, and assessed the risk of surgery by using ultrasound to detect the distance between the popliteal artery and the posterior edge of tibial plateau bone cortex.ResultsIn all 14 cadaveric specimens, the PCL tibial insertions were located completely within the posterior medial compartment of the knee. The distance between the center of the SP tunnel and the the articular surface of tibial plateau was 9.4 ± 0.4 mm. All SP tunnels retained an intact posterior wall, which was 1.6 ± 0.3 mm from the distal reflection of the posterior capsule. The distances between the center of the SP tunnel and the the articular surface of tibial plateau, the champagne glass drop-off were 9.2 ± 0.4 mm (ICC: 0.932, 95%CI 0.806–0.978) and 1.5 ± 0.2 mm (ICC:0.925, 95%CI 0.788–0.975) in CT image. Compared with the posterior capsule, the posterior septum contained more vascular structures. Last, all 12 patients successfully established low tibial tunnels under arthroscopy, and the distance between the posterior edge of tibial plateau bone cortex and the popliteal artery was 7.8 ± 0.3, 9.4 ± 0.4 and 7.4 ± 0.3 mm at 30°, 60° and 90° flexion angels after filling with water and supporting with shaver in posterior-medial compartment of knee joint.ConclusionsA modified low tibial tunnel could be established in the PCL anatomical footprint by using the posterior septum and posterior capsule as landmarks.

Material Properties of Fiber Bundles of the Superficial Medial Collateral Ligament of the Knee Joint.

The superficial medial collateral ligament (sMCL) of the human knee joint has functionally separate anterior and posterior fiber bundles. The two bundles are alternatively loaded as the knee flexion angle changes during walking. To date, the two bundles are usually not distinguished in knee ligament simulations because there has been little information about their material properties. In this study, we conducted quasi-static tensile tests on the sMCL of matured porcine stifle joints and obtained the material properties of the anterior bundle (AB), posterior bundle (PB), and whole ligament (WL). AB and PB have similar failure stress but different threshold strain, modulus, and failure strain. As a result, we recommend assigning different material properties (i.e., modulus and failure strain) to the two fiber bundles to realize biofidelic ligament responses in human body models. However, it is often inconvenient to perform tensile tests on AB and PB. Hence, we proposed a microstructural model-based approach to predict the material properties of AB and PB from the test results of WL. Such obtained modulus values of AB and PB had an error of 2% and 0.3%, respectively, compared with those measured from the tests. This approach can reduce the experimental cost for acquiring the needed mechanical property data for simulations.

Bi-Exponential 3D UTE-T1ρ Relaxation Mapping of Ex Vivo Human Knee Patellar Tendon at 3T.

Introduction: The objective of this study was to assess the bi-exponential relaxation times and fractions of the short and long components of the human patellar tendon ex vivo using three-dimensional ultrashort echo time T1ρ (3D UTE-T1ρ) imaging. Materials and Methods: Five cadaveric human knee specimens were scanned using a 3D UTE-T1ρ imaging sequence on a 3T MR scanner. A series of 3D UTE-T1ρ images were acquired and fitted using single-component and bi-component models. Single-component exponential fitting was performed to measure the UTE-T1ρ value of the patellar tendon. Bi-component analysis was performed to measure the short and long UTE-T1ρ values and fractions. Results: The single-component analysis showed a mean single-component UTE-T1ρ value of 8.4 ± 1.7 ms for the five knee patellar tendon samples. Improved fitting was achieved with bi-component analysis, which showed a mean short UTE-T1ρ value of 5.5 ± 0.8 ms with a fraction of 77.6 ± 4.8%, and a mean long UTE-T1ρ value of 27.4 ± 3.8 ms with a fraction of 22.4 ± 4.8%. Conclusion: The 3D UTE-T1ρ sequence can detect the single- and bi-exponential decay in the patellar tendon. Bi-component fitting was superior to single-component fitting.

Model Properties and Clinical Application in the Finite Element Analysis of Knee Joint: A Review.

The knee is the most complex joint in the human body, including bony structures like the femur, tibia, fibula, and patella, and soft tissues like menisci, ligaments, muscles, and tendons. Complex anatomical structures of the knee joint make it difficult to conduct precise biomechanical research and explore the mechanism of movement and injury. The finite element model (FEM), as an important engineering analysis technique, has been widely used in many fields of bioengineering research. The FEM has advantages in the biomechanical analysis of objects with complex structures. Researchers can use this technology to construct a human knee joint model and perform biomechanical analysis on it. At the same time, finite element analysis can effectively evaluate variables such as stress, strain, displacement, and rotation, helping to predict injury mechanisms and optimize surgical techniques, which make up for the shortcomings of traditional biomechanics experimental research. However, few papers introduce what material properties should be selected for each anatomic structure of knee FEM to meet different research purposes. Based on previous finite element studies of the knee joint, this paper summarizes various modeling strategies and applications, serving as a reference for constructing knee joint models and research design.

LATERAL RIM VARIABLE ANGLE LOCKED PLATING VERSUS TENSION BAND WIRING OF SIMPLE AND COMPLEX PATELLA FRACTURES: A BIOMECHANICAL STUDY

Treatment of both simple and complex patella fractures is a challenging clinical problem. The aim of this study was to investigate the biomechanical performance of recently developed lateral rim variable angle locking plates versus tension band wiring used for fixation of simple and complex patella fractures.Twelve pairs of human anatomical knees were used to simulate either two-part transverse simple AO/OTA 34C1 or five-part complex AO/OTA 34C3 patella fractures by means of osteotomies, with each fracture model created in six pairs. The complex fracture pattern was characterized by a medial and a lateral proximal fragment, together with an inferomedial, an inferolateral, and an inferior fragment mimicking comminution around the distal patellar pole. The specimens with simple fractures were pairwise assigned for fixation with either tension band wiring through two parallel cannulated screws, or a lateral rim variable angle locking plate. The knees with complex fractures were pairwise treated with either tension band wiring through two parallel cannulated screws plus circumferential cerclage wiring, or a lateral rim variable angle locking plate.Each specimen was tested over 5000 cycles by pulling on the quadriceps tendon, simulating active knee extension and passive knee flexion within the range of 90° flexion to full knee extension. Interfragmentary movements were captured via motion tracking.For both fracture types, the longitudinal and shear articular displacements measured between the proximal and distal fragments at the central patella aspect between 1000 and 5000 cycles, together with the relative rotations of these fragments around the mediolateral axis were all significantly smaller following the lateral rim variable angle locked plating compared with tension band wiring, p&lt;0.01.Lateral rim locked plating of both simple and complex patella fractures provides superior construct stability versus tension band wiring under dynamic loading.

MYOKINE FUNDC5 COMPROMISES MITOCHONDRIAL DYSFUNCTION IN OSTEOARTHRITIS

Chondrocytic activity is downregulated by compromised autophagy and mitochondrial dysfunction to accelerate the development of osteoarthritis (OA). Irisin is a cleaved form of fibronectin type III domain containing 5 (FNDC5) and known to regulate bone turnover and muscle homeostasis. However, little is known about the role of irisin in chondrocytes and the development of OA. This talk will shed light on FNDC5 expression by human articular chondrocytes and compare normal and osteoarthritic cells with respect to autophagosome marker LC3-II and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG). In chondrocytes in vitro, irisin improves IL-1β-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production. Irisin further suppressed Sirt3 and UCP- 1 to improve mitochondrial membrane potential, ATP production, and catalase. This attenuated IL-1β-mediated production of reactive oxygen species, mitochondrial fusion, mitophagy, and autophagosome formation. In a surgical murine model of destabilization of the medial meniscus (DMM) intra-articular administration of irisin alleviates symptoms like cartilage erosion and synovitis. Furthermore, gait profiles of the treated limbs improved. In chondrocytes, irisin treatment upregulates autophagy, 8-OHdG and apoptosis in cartilage of DMM limbs. Loss of FNDC5 in chondrocytes correlates with human knee OA and irisin repressed inflammation-mediated oxidative stress and deficient extracellular matrix synthesis through retaining mitochondrial biogenesis and autophagy. The talk sheds new light on the chondroprotective actions of this myokine and highlights the remedial effects of irisin during progression of OA.

Role of Lateral Extra-articular Tenodesis in Restraining Internal Tibial Rotation: In Vitro Biomechanical Assessment of Lateral Tissue Engagement

Background: The way in which force increases in the anterolateral tissues and the lateral extra-articular tenodesis (LET) tissue to resist internal rotation (IR) of the tibia after anterior cruciate ligament (ACL) reconstruction in isolation and after LET augmentation, respectively, is not well understood. Purpose: (1) To compare in a cadaveric model how force increases (ie, engages) in the anterolateral tissues with IR of the tibia after isolated ACL reconstruction and in the LET tissue after augmentation of the ACL reconstruction with LET and (2) to determine whether IR of the tibia is related to engagement of the LET tissue. Study Design: Controlled laboratory study. Methods: IR moments were applied to 9 human cadaveric knees at 0°, 30°, 60°, and 90° of flexion using a robotic manipulator. Each knee was tested in 2 states: (1) after isolated ACL reconstruction with intact anterolateral tissues and (2) after LET was performed using a modified Lemaire technique with the LET tissue fixed at 60° of flexion under 44 N of tension. Resultant forces carried by the anterolateral tissues and the LET tissue were determined via superposition. The way force increased in these tissues was characterized via parameters of tissue engagement, namely in situ slack, in situ stiffness, and tissue force at peak applied IR moment, and then compared (α < .05). IR was related to parameters of engagement of the LET tissue via simple linear regression (α < .05). Results: The LET tissue exhibited less in situ slack than the anterolateral tissues at 30°, 60°, and 90° of flexion (P≤ .04) and greater in situ stiffness at 30° and 90° of flexion (P≤ .043). The LET tissue carried greater force at the peak applied IR moment at 0° and 30° of flexion (P≤ .01). IR was related to the in situ slack of the LET tissue (R2≥ 0.88; P≤ .0003). Conclusion: LET increased restraint to IR of the tibia compared with the anterolateral tissue, particularly at 30°, 60°, and 90° of flexion. IR of the tibia was positively associated with in situ slack of the LET tissue. Clinical Relevance: Fixing the LET at 60° of flexion still provided IR restraint in the more functionally relevant flexion angle of 30°. Surgeons should pay close attention to the angle of internal and/or external tibial rotation when fixing the LET tissue intraoperatively because this surgical parameter is related to in situ slack of the LET tissue and, therefore, the amount of IR of the tibia.

Medial Meniscus Posterior Root Tears Lead to Changes in Joint Contact Mechanics at Low Flexion Angles During Simulated Gait

Background: Previous biomechanical studies evaluating medial meniscus posterior root tears (MMPRTs) are limited to low loads applied at specified loading angles, which cannot capture the effects of MMPRTs during the multidirectional forces and moments placed across the knee during physiological activities. Purpose: To quantify the effects of MMPRTs on knee joint contact mechanics during simulated gait. Study Design: Controlled laboratory study. Methods: Six human cadaveric knees were mounted on a robotic simulator programmed to apply dynamic forces, moments, and flexion angles to mimic level walking. Twelve cycles of multidirectional and dynamic standard gait input waveforms, normalized to specimen-specific body weight, were applied to the following conditions: (1) native, intact meniscus and (2) MMPRT. Peak contact stress, contact area, and the position of the weighted center of contact across the medial tibial plateau throughout the stance phase of gait were quantified using an electronic sensor placed across the medial tibial plateau. The difference between the intact state and MMPRT condition was calculated for each metric, and then the means and 95% CIs were computed. Results: Despite heterogeneity in knee contact forces, MMPRTs significantly increased peak contact stress by a mean of 2 MPa across 20% to 37% of the simulated gait cycle and significantly decreased the contact area by a mean of 200 mm2 across 16% to 60% of the simulated gait cycle in comparison with the native state. There was no significant difference in the position of the weighted center of contact, in either the anterior-posterior or medial-lateral directions, after MMPRT. Conclusion: MMPRTs led to both a significant increase in peak contact stress and decreased contact areas for a portion of the simulated gait cycle ranging from 20% to 37% of gait, during which time the femur was flexed <15°. Clinical Relevance: Contact mechanics are significantly affected after MMPRTs during early to midstance and at knee flexion angles lower than demonstrated previously. These data provide further biomechanical justification for treating MMPRTs.

Validation of a Finite Element Simulation for Predicting Individual Knee Joint Kinematics.

Goal: We introduce an in-vivo validated finite element (FE) simulation approach for predicting individual knee joint kinematics. Our vision is to improve clinicians' understanding of the complex individual anatomy and potential pathologies to improve treatment and restore physiological joint kinematics. Methods: Our 3D FE modeling approach for individual human knee joints is based on segmentation of anatomical structures extracted from routine static magnetic resonance (MR) images. We validate the predictive abilities of our model using static MR images of the knees of eleven healthy volunteers in dedicated knee poses, which are achieved using a customized MR-compatible pneumatic loading device. Results: Our FE simulations reach an average translational accuracy of 2 mm and an average angular accuracy of 1[Formula: see text] compared to the reference knee pose. Conclusions: Reaching high accuracy, our individual FE model can be used in the decision-making process to restore knee joint stability and functionality after various knee injuries.