Impact of degeneration and material pairings on cartilage friction: Cartilage versus glass.

The association of knee joint osteoarthritis and altered frictional properties of the degenerated cartilage remains ambiguous, because previous in vitro studies did not consider the characteristic loads and velocities during gait. Therefore, the aim of this study was to quantify the friction behavior of degenerated human cartilage under characteristic stance and swing phase conditions. A dynamic pin-on-plate tribometer was used to test the tribological systems of cartilage against cartilage and cartilage against glass, both with synthetic synovial fluid as lubricant. Using the International Cartilage Repair Society classification, the cartilage samples were assigned to a mildly or a severely degenerated group before testing. Friction coefficients were calculated under stance and swing phase conditions at the beginning of the test and after 600 s of testing. The most important finding of this study is that cartilage against glass couplings displayed significantly higher friction for the severely degenerated samples compared to the mildly degenerated ones, whereas cartilage against cartilage couplings only indicated slight tendencies under the observed test conditions. Consequently, care should be taken when transferring in vitro findings from cartilage against cartilage couplings to predict the friction behavior in vivo. Therefore, we recommend in vitro tribological testing methods which account for gait-like loading conditions and to replicate physiological material pairings, particularly in preclinical medical device validation studies.

Impact of hyaluronic acid injection on the knee joint friction.

PURPOSE: The purpose of this in vitro study was to investigate whether or not hyaluronic acid supplementation improves knee joint friction during osteoarthritis progression under gait-like loading conditions. METHODS: Twelve human cadaveric knee joints were equally divided into mild and moderate osteoarthritic groups. After initial conservative preparation, a passive pendulum setup was used to test the whole joints under gait-like conditions before and after hyaluronic acid supplementation. The friction-related damping properties given by the coefficient of friction µ and the damping coefficient c (in kg m2/s) were calculated from the decaying flexion-extension motion of the knee. Subsequently, tibial and femoral cartilage and meniscus samples were extracted from the joints and tested in an established dynamic pin-on-plate tribometer using synthetic synovial fluid followed by synthetic synovial fluid supplemented with hyaluronic acid as lubricant. Friction was quantified by calculating the coefficient of friction. RESULTS: In the pendulum tests, the moderate OA group indicated significantly lower c0 values (p < 0.05) under stance phase conditions and significantly lower µ0 (p = 0.01) values under swing phase conditions. No degeneration-related statistical differences were found for µend or cend. Friction was not significantly different (p > 0.05) with regard to mild and moderate osteoarthritis in the pin-on-plate tests. Additionally, hyaluronic acid did not affect friction in both, the pendulum (p > 0.05) and pin-on-plate friction tests (p > 0.05). CONCLUSION: The results of this in vitro study suggested that the friction of cadaveric knee joint tissues does not increase with progressing degeneration. Moreover, hyaluronic acid viscosupplementation does not lead to an initial decrease in knee joint friction.

Magnetic-Responsive Carbon Nanotubes Composite Scaffolds for Chondrogenic Tissue Engineering.

The demand for engineered scaffolds capable of delivering multiple cues to cells continues to grow as the interplay between cell fate with microenvironmental and external cues is revealed. Emphasis has been given to develop stimuli-responsive scaffolds. These scaffolds are designed to sense an external stimulus triggering a specific response (e.g., change in the microenvironment, release therapeutics, etc.) and then initiate/modulate a desired biofunction. Here, magnetic-responsive carboxylated multi-walled carbon nanotubes (cMWCNTs) are integrated into 3D collagen/polylactic acid (PLA) scaffold via a reproducible filtration-based method. The integrity and biomechanical performance of the collagen/PLA scaffolds are preserved after cMWCNT integration. In vitro safety assessment of cMWCNT/collagen/PLA scaffolds shows neither cytotoxicity effects nor macrophage pro-inflammatory response, supporting further in vitro studies. The cMWCNT/collagen/PLA scaffolds enhance chondrocytes metabolic activity while maintaining high cell viability and extracellular matrix (i.e., type II collagen and aggrecan) production. Comprehensive in vitro study applying static and pulsed magnetic field on seeded scaffolds shows no specific cell response in dependence with the applied field. This result is independent of the presence or absence of cMWCNT into the collagen/PLA scaffolds. Taken together, these findings provide additional evidence of the benefits to exploit the CNTs outstanding properties in the design of stimuli-responsive scaffolds.

Knee Joint Menisci Are Shock Absorbers: A Biomechanical In-Vitro Study on Porcine Stifle Joints.

The aim of this biomechanical in vitro study was to answer the question whether the meniscus acts as a shock absorber in the knee joint or not. The soft tissue of fourteen porcine knee joints was removed, leaving the capsuloligamentous structures intact. The joints were mounted in 45° neutral knee flexion in a previously validated droptower setup. Six joints were exposed to an impact load of 3.54 J, and the resultant loss factor (η) was calculated. Then, the setup was modified to allow sinusoidal loading under dynamic mechanical analysis (DMA) conditions. The remaining eight knee joints were exposed to 10 frequencies ranging from 0.1 to 5 Hz at a static load of 1210 N and a superimposed sinusoidal load of 910 N (2.12 times body weight). Forces (F) and deformation (l) were continuously recorded, and the loss factor (tan δ) was calculated. For both experiments, four meniscus states (intact, medial posterior root avulsion, medial meniscectomy, and total lateral and medial meniscectomy) were investigated. During the droptower experiments, the intact state indicated a loss factor of η = 0.1. Except for the root avulsion state (-15%, p = 0.12), the loss factor decreased (p < 0.046) up to 68% for the total meniscectomy state (p = 0.028) when compared to the intact state. Sinusoidal DMA testing revealed that knees with an intact meniscus had the highest loss factors, ranging from 0.10 to 0.15. Any surgical manipulation lowered the damping ability: Medial meniscectomy resulted in a reduction of 24%, while the resection of both menisci lowered tan δ by 18% compared to the intact state. This biomechanical in vitro study indicates that the shock-absorbing ability of a knee joint is lower when meniscal tissue is resected. In other words, the meniscus contributes to the shock absorption of the knee joint not only during impact loads, but also during sinusoidal loads. The findings may have an impact on the rehabilitation of young, meniscectomized patients who want to return to sports. Consequently, such patients are exposed to critical loads on the articular cartilage, especially when performing sports with recurring impact loads transmitted through the knee joint surfaces.

Meniscus Injury and its Surgical Treatment Does not Increase Initial Whole Knee Joint Friction.

While it is generally accepted that traumatic meniscus pathologies lead to degenerative articular cartilage changes in the mid-to long-term and consecutively to post-traumatic osteoarthritis (PTOA), very little is known about how such injuries initiate tribological changes within the knee and their possible impact on PTOA acceleration. Therefore, the aim of this study was to investigate the influence of three different medial meniscus states (intact, posterior root tear, total meniscectomy) on the initial whole knee joint friction. Six ovine knee joints were tested in a passive pendulum friction testing device under an axial load of 250 N and an initial deflection of 12°, representing swing phase conditions, and under an axial load of 1000 N and an initial deflection of 5°, simulating stance phase conditions. To additionally consider the influence of the time-dependent viscoelastic nature of the knee joint soft tissues on whole joint friction, the tests were performed twice, directly following load application and after 20 min creep loading of either 250 N or 1000 N axial load. On the basis of a three-dimensional joint kinematic analysis, the energy loss during the passive joint motion was analyzed, which allowed considerations on frictional and damping processes within the joint. The so-called "whole knee joint" friction was evaluated using the boundary friction model from Stanton and a viscous friction model from Crisco et al., both analyzing the passive joint flexion-extension motion in the sagittal plane. Significantly lower friction coefficients were observed in the simulated swing phase after meniscectomy (p < 0.05) compared to the intact state. No initial whole joint friction differences between the three meniscus states (p > 0.05) were found under stance phase conditions. Soft tissue creeping significantly increased all the determined friction coefficients (p < 0.05) after resting under load for 20 min. The exponential decay function of the viscous friction model provided a better fit (R 2∼0.99) to the decaying flexion-extension data than the linear decay function of the boundary friction model (R 2∼0.60). In conclusion, this tribological in vitro study on ovine knee joints indicated that neither a simulated posterior medial meniscus root tear nor the removal of the medial meniscus resulted in an initially increased whole joint friction.

Articular cartilage and meniscus reveal higher friction in swing phase than in stance phase under dynamic gait conditions.

Most previous studies investigated the remarkably low and complex friction properties of meniscus and cartilage under constant loading and motion conditions. However, both load and relative velocity within the knee joint vary considerably during physiological activities. Hence, the question arises how friction of both tissues is affected by physiological testing conditions occurring during gait. As friction properties are of major importance for meniscal replacement devices, the influence of these simulated physiological testing conditions was additionally tested for a potential meniscal implant biomaterial. Using a dynamic friction testing device, three different friction tests were conducted to investigate the influence of either just varying the motion conditions or the normal load and also to replicate the physiological gait conditions. It could be shown for the first time that the friction coefficient during swing phase was statistically higher than during stance phase when varying both loading and motion conditions according to the physiological gait pattern. Further, the friction properties of the exemplary biomaterial were also higher, when tested under dynamic gait parameters compared to static conditions, which may suggest that static conditions can underestimate the friction coefficient rather than reflecting the in vivo performance.

Biomechanical, structural and biological characterisation of a new silk fibroin scaffold for meniscal repair.

Meniscal injury is typically treated surgically via partial meniscectomy, which has been shown to cause cartilage degeneration in the long-term. Consequently, research has focused on meniscal prevention and replacement. However, none of the materials or implants developed for meniscal replacement have yet achieved widespread acceptance or demonstrated conclusive chondroprotective efficacy. A redesigned silk fibroin scaffold, which already displayed promising results regarding biocompatibility and cartilage protection in a previous study, was characterised in terms of its biomechanical, structural and biological functionality to serve as a potential material for permanent partial meniscal replacement. Therefore, different quasi-static but also dynamic compression tests were performed. However, the determined compressive stiffness (0.56 ±â€¯0.31 MPa and 0.30 ±â€¯0.12 MPa in relaxation and creep configuration, respectively) was higher in comparison to the native meniscal tissue, which could potentially disturb permanent integration into the host tissue. Nevertheless, µ-CT analysis met the postulated requirements for partial meniscal replacement materials in terms of the microstructural parameters, like mean pore size (215.6 ±â€¯10.9 µm) and total porosity (80.1 ±â€¯4.3%). Additionally, the biocompatibility was reconfirmed during cell culture experiments. The current study provides comprehensive mechanical and biological data for the characterisation of this potential replacement material. Although some further optimisation of the silk fibroin scaffold may be advantageous, the silk fibroin scaffold showed sufficient biomechanical competence to support loads already in the early postoperative phase.

Diet-Induced Obesity Affects Muscle Regeneration After Murine Blunt Muscle Trauma-A Broad Spectrum Analysis.

Injury to skeletal muscle affects millions of people worldwide. The underlying regenerative process however, is a very complex mechanism, time-wise highly coordinated, and subdivided in an initial inflammatory, a regenerative and a remodeling phase. Muscle regeneration can be impaired by several factors, among them diet-induced obesity (DIO). In order to evaluate if obesity negatively affects healing processes after trauma, we utilized a blunt injury approach to damage the extensor iliotibialis anticus muscle on the left hind limb of obese and normal weight C57BL/6J without showing any significant differences in force input between normal weight and obese mice. Magnetic resonance imaging (MRI) of the injury and regeneration process revealed edema formation and hemorrhage exudate in muscle tissue of normal weight and obese mice. In addition, morphological analysis of physiological changes revealed tissue necrosis, immune cell infiltration, extracellular matrix (ECM) remodeling, and fibrosis formation in the damaged muscle tissue. Regeneration was delayed in muscles of obese mice, with a higher incidence of fibrosis formation due to hampered expression levels of genes involved in ECM organization. Furthermore, a detailed molecular fingerprint in different stages of muscle regeneration underlined a delay or even lack of a regenerative response to injury in obese mice. A time-lapse heatmap determined 81 differentially expressed genes (DEG) with at least three hits in our model at all-time points, suggesting key candidates with a high impact on muscle regeneration. Pathway analysis of the DEG revealed five pathways with a high confidence level: myeloid leukocyte migration, regulation of tumor necrosis factor production, CD4-positive, alpha-beta T cell differentiation, ECM organization, and toll-like receptor (TLR) signaling. Moreover, changes in complement-, Wnt-, and satellite cell-related genes were found to be impaired in obese animals after trauma. Furthermore, histological satellite cell evaluation showed lower satellite cell numbers in the obese model upon injury. Ankrd1, C3ar1, Ccl8, Mpeg1, and Myog expression levels were also verified by qPCR. In summary, increased fibrosis formation, the reduction of Pax7+ satellite cells as well as specific changes in gene expression and signaling pathways could explain the delay of tissue regeneration in obese mice post trauma.

Functional and Molecular Characterization of a Novel Traumatic Peripheral Nerve-Muscle Injury Model.

Traumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mice. We compare nerve regeneration in this novel peripheral nerve trauma model with the established surgical nerve injury along several parameters. These include gene expression, histological and functional facial motoneuron (FMN) regeneration, facial nerve degeneration, immune cell activation and muscle damage. Regeneration-associated genes (RAGs; e.g., Atf3) were strongly induced in FMNs subjected to traumatic and surgical injury. Regeneration of FMNs and functional recovery of whisker movement were faster in traumatic versus complete surgical injury, thus cutting down experimentation time. Wallerian degeneration of distal nerve stumps was readily observed in this novel trauma injury model. Importantly, drop tower-inflicted facial nerve injury resulted in muscle damage, activation of muscle satellite cell markers (PAX7) and pronounced infiltration of immune cells to the injury site only in this model but not upon surgical nerve transection. Thus, we provide a novel rodent PNS trauma model that can be easily adopted to other PNS nerves such as the sciatic nerve. Since this nerve trauma model replicates multiple tissue damage frequently encountered in clinical routine, it will be well suited to identify molecular and cellular mechanisms of PNS nerve repair in wild-type and genetically modified rodents.