Human articular cartilage is orthotropic where microstructure, micromechanics, and chemistry vary with depth and split-line orientation.

OBJECTIVE: Quantitative, micrometer length scale assessment of human articular cartilage is essential to enable progress toward new functional tissue engineering approaches, including utilization of emerging 3D bioprinting technologies, and for improved computational modeling of the osteochondral unit. Thus the objective of this study was to characterize the structural organization, material properties, and chemical composition of human skeletally mature articular cartilage with respect to depth and defined morphological features: normal to the articulating surface, parallel to the split-line, and transverse to the split-line. METHOD: Three samples from the lateral femoral condyles of 4 healthy adult donors (55-61 years old) were evaluated via histology, second harmonic generation, microindentation, and Raman spectroscopy. All metrics were evaluated as a function of depth and direction relative to the split-line. RESULTS: All donors presented with intact and healthy tissue. Collagen fiber orientation varied significantly between testing directions and with increasing depth from the articular surface. Both compressive and tensile modulus increased significantly with depth and differed across the middle and deep zones and depended on orthogonal direction relative to the split-line. Similarly, matrix components varied with both depth and direction, where chondroitin sulfate steadily increased with depth while collagen prevalence was highest in the surface layer. CONCLUSIONS: Microscale measurements of human articular cartilage demonstrate that properties are both depth-dependent and orthotropic and depend on the underlying tissue structure and composition. These findings improve upon existing knowledge establishing more accurate measurements, with greater degree of depth and spatial specificity, as inputs for tissue engineering and computational modeling.

Chondrocyte viability is lost during high-rate impact loading by transfer of amplified strain, but not stress, to pericellular and cellular regions.

OBJECTIVE: Deleterious impact loading to cartilage initiates post-traumatic osteoarthritis (OA). While cytokine and enzyme levels regulate disease progression, specific mechanical cues that elucidate cellular OA origins merit further investigation. We defined the dominant pericellular and cellular strain/stress transfer mechanisms following bulk-tissue injury associated with cell death. METHOD: Using an in vitro model, we investigated rate-dependent loading and spatial localization of cell viability in acute indentation and time-course studies. Atomic force microscopy (AFM) and magnetic resonance imaging (MRI) confirmed depth-wise changes in cartilage micro-/macro-mechanics and structure post-indentation. To understand the transfer of loading to cartilage domains, we computationally modeled full-field strain and stress measures in interstitial matrix, pericellular and cellular regions. RESULTS: Chondrocyte viability decreased following rapid impact (80%/s) vs slow loading (0.1%/s) or unloaded controls. Viability was lost immediately during impact within regions near the indenter-tissue contact but did not change over 7 days of tissue culture. AFM studies revealed a loss of stiffness following 80%/s loading, and MRI studies confirmed an increased tensile and shear strain, but not relaxometry. Image-based patterns of chondrocyte viability closely matched computational estimates of amplified maximum principal and shear strain in interstitial matrix, pericellular and cellular regions. CONCLUSION: Rapid indentation worsens chondrocyte death and degrades cartilage matrix stiffness in indentation regions. Cell death at high strain rates may be driven by elevated tensile strains, but not matrix stress. Strain amplification beyond critical thresholds in the pericellular matrix and cells may define a point of origin for early damage in post-traumatic OA.

Propagation of microcracks in collagen networks of cartilage under mechanical loads.

OBJECTIVE: We recently demonstrated that low-energy mechanical impact to articular cartilage, usually considered non-injurious, can in fact cause microscale cracks (widths <30µm) in the collagen network of visually pristine human cartilage. While research on macro-scale cracks in cartilage and microcracks in bone abounds, how microcracks within cartilage initiate and propagate remains unknown. We quantified the extent to which microcracks initiate and propagate in the collagen network during mechanical loading representative of normal activities. DESIGN: We tested 76 full-thickness, cylindrical osteochondral plugs. We imaged untreated specimens (pristine phase) via second harmonic generation and assigned specimens to three low-energy impact groups (none, low, high), and thereafter to three cyclic compression groups (none, low, high) which simulate walking. We re-imaged specimens in the post-impact and post-cyclic compression phases to identify and track microcracks. RESULTS: Microcracks in the network of collagen did not present in untreated controls but did initiate and propagate under mechanical treatments. We found that the length and width of microcracks increased from post-impact to post-cyclic compression in tracked microcracks, but neither depth nor angle presented statistically significant differences. CONCLUSIONS: The microcracks we initiated under low-energy impact loading increased in length and width during subsequent cyclic compression that simulated walking. The extent of this propagation depended on the combination of impact and cyclic compression. More broadly, the initiation and propagation of microcracks may characterize pathogenesis of osteoarthritis, and may suggest therapeutic targets for future studies.

Raman spectroscopy-based water content is a negative predictor of articular human cartilage mechanical function.

OBJECTIVE: Probing the change in water content is an emerging approach to assess early diagnosis of osteoarthritis (OA). We herein developed a new method to assess hydration status of cartilage nondestructively using Raman spectroscopy (RS), and showed association of Raman-based water and organic content measurement with mechanical properties of cartilage. We further compared Raman-based water measurement to gravimetric and magnetic resonance imaging (MRI)-based water measurement. DESIGN: Eighteen cadaveric human articular cartilage plugs from 6 donors were evenly divided into two age groups: young (n = 9, mean age: 29.3 ± 6.6) and old (n = 9, mean age: 64.0 ± 1.5). Water content in cartilage was measured using RS, gravimetric, and MRI-based techniques. Using confined compression creep test, permeability and aggregate modulus were calculated. Regression analyses were performed among RS parameters, MRI parameter, permeability, aggregate modulus and gravimetrically measured water content. RESULTS: Regardless of the method used to calculate water content (gravimetric, RS and MRI), older cartilage group consistently had higher water content compared to younger group. There was a stronger association between gravimetric and RS-based water measurement (Rg2 = 0.912) than between gravimetric and MRI-based water measurement (Rc2 = 0.530). Gravimetric and RS-based water contents were significantly correlated with permeability and aggregate modulus whereas MRI-based water measurement was not. CONCLUSION: RS allows for quantification of different water compartments in cartilage nondestructively, and estimation of up to 82% of the variation observed in the permeability and aggregate modulus of articular cartilage. RS has the potential to be used clinically to monitor cartilage quality noninvasively or minimally invasively with Raman probe during arthroscopy procedures.

Functional assessment of strains around a full-thickness and critical sized articular cartilage defect under compressive loading using MRI.

OBJECTIVE: The objective of this study was to evaluate the effect of full-thickness chondral defects on intratissue deformation patterns and matrix constituents in an experimental model mimicking in vivo cartilage-on-cartilage contact conditions. DESIGN: Pairs of bovine osteochondral explants, in a unique cartilage-on-cartilage model system, were compressed uniaxially by 350 N during 2 s loading and 1.4 s unloading cycles (≈1700 repetitions). Tissue deformations under quasi-steady state load deformation response were measured with displacement encoded imaging with stimulated echoes (DENSE) in a 9.4 T magnetic resonance imaging (MRI) scanner. Pre- and post-loading, T1, T2 and T1ρ relaxation time maps were measured. We analyzed differences in strain patterns and relaxation times between intact cartilage (n = 8) and cartilage in which a full-thickness and critical sized defect was created (n = 8). RESULTS: Under compressive loading, strain magnitudes were elevated at the defect rim, with elevated tensile and compressive principal strains (Δϵmax = 4.2%, P = 0.02; Δϵmin = -4.3%, P = 0.02) and maximum shear strain at the defect rim (Δγmax = 4.4%, P = 0.007). The opposing cartilage showed minimal increase in strain patterns at contact with the defect rim but decreased strains opposing the defect. After defect creation, T1, T2 and T1ρ relaxation times were elevated at the defect rim only. Following loading, the overall relaxations times of the defect tissue and especially at the rim, increased compared to intact cartilage. CONCLUSIONS: This study demonstrates that the local biomechanical changes occurring after defect creation may induce tissue damage by increasing shear strains and depletion of cartilage constituents at the defect rim under compressive loading.

Cartilage-on-cartilage contact: effect of compressive loading on tissue deformations and structural integrity of bovine articular cartilage.

OBJECTIVE: This study aims to characterize the deformations in articular cartilage under compressive loading and link these to changes in the extracellular matrix constituents described by magnetic resonance imaging (MRI) relaxation times in an experimental model mimicking in vivo cartilage-on-cartilage contact. DESIGN: Quantitative MRI images, T1, T2 and T1ρ relaxation times, were acquired at 9.4T from bovine femoral osteochondral explants before and immediately after loading. Two-dimensional intra-tissue displacement and strain fields under cyclic compressive loading (350N) were measured using the displacement encoding with stimulated echoes (DENSE) method. Changes in relaxation times in response to loading were evaluated against the deformation fields. RESULTS: Deformation fields showed consistent patterns among all specimens, with maximal strains at the articular surface that decrease with tissue depth. Axial and transverse strains were maximal around the center of the contact region, whereas shear strains were minimal around the contact center but increased towards contact edges. A decrease in T2 and T1ρ was observed immediately after loading whereas the opposite was observed for T1. No correlations between cartilage deformation patterns and changes in relaxation times were observed. CONCLUSIONS: Displacement encoding combined with relaxometry by MRI can noninvasively monitor the cartilage biomechanical and biochemical properties associated with loading. The deformation fields reveal complex patterns reflecting the depth-dependent mechanical properties, but intra-tissue deformation under compressive loading does not correlate with structural and compositional changes. The compacting effect of cyclic compression on the cartilage tissue was revealed by the change in relaxation time immediately after loading.

Machine learning classification of OARSI-scored human articular cartilage using magnetic resonance imaging.

OBJECTIVE: The purpose of this study is to evaluate the ability of machine learning to discriminate between magnetic resonance images (MRI) of normal and pathological human articular cartilage obtained under standard clinical conditions. METHOD: An approach to MRI classification of cartilage degradation is proposed using pattern recognition and multivariable regression in which image features from MRIs of histologically scored human articular cartilage plugs were computed using weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHRM). The WND-CHRM method was first applied to several clinically available MRI scan types to perform binary classification of normal and osteoarthritic osteochondral plugs based on the Osteoarthritis Research Society International (OARSI) histological system. In addition, the image features computed from WND-CHRM were used to develop a multiple linear least-squares regression model for classification and prediction of an OARSI score for each cartilage plug. RESULTS: The binary classification of normal and osteoarthritic plugs yielded results of limited quality with accuracies between 36% and 70%. However, multiple linear least-squares regression successfully predicted OARSI scores and classified plugs with accuracies as high as 86%. The present results improve upon the previously-reported accuracy of classification using average MRI signal intensities and parameter values. CONCLUSION: MRI features detected by WND-CHRM reflect cartilage degradation status as assessed by OARSI histologic grading. WND-CHRM is therefore of potential use in the clinical detection and grading of osteoarthritis.

Optical clearing in collagen- and proteoglycan-rich osteochondral tissues.

OBJECTIVE: Recent developments in optical clearing and microscopy technology have enabled the imaging of intact tissues at the millimeter scale to characterize cells via fluorescence labeling. While these techniques have facilitated the three-dimensional (3D) cellular characterization within brain and heart, study of dense connective tissues of the musculoskeletal system have been largely unexplored. Here, we quantify how optical clearing impacted the cell and tissue morphology of collagen-, proteoglycan-, and mineral-rich cartilage and bone from the articulating knee joint. METHODS: Water-based fructose solutions were used for optical clearing of bovine osteochondral tissues, followed by imaging with transmission and confocal microscopy. To confirm preservation of tissue structure during the clearing process, samples were mechanically tested in unconfined compression and visualized by cryo-SEM. RESULTS: Optical clearing enhanced light transmission through cartilage, but not subchondral bone regions. Fluorescent staining and immunolabeling was preserved through sample preparations, enabling imaging to cartilage depths five times deeper than previously reported, limited only by the working distance of the microscope objective. Chondrocyte volume remained unchanged in response to, and upon the reversal, of clearing. Equilibrium modulus increased in cleared samples, and was attributed to exchange of interstitial fluid with the more viscous fructose solution, but returned to control levels upon unclearing. In addition, cryo-SEM-based analysis of cartilage showed no ultrastructural changes. CONCLUSION: We anticipate large-scale microscopy of diverse connective tissues will enable the study of intact, 3D interfaces (e.g., osteochondral) and cellular connectivity as a function of development, disease, and regeneration, which have been previously hindered by specimen opacity.

Functional imaging in OA: role of imaging in the evaluation of tissue biomechanics.

Functional imaging refers broadly to the visualization of organ or tissue physiology using medical image modalities. In load-bearing tissues of the body, including articular cartilage lining the bony ends of joints, changes in strain, stress, and material properties occur in osteoarthritis (OA), providing an opportunity to probe tissue function through the progression of the disease. Here, biomechanical measures in cartilage and related joint tissues are discussed as key imaging biomarkers in the evaluation of OA. Emphasis will be placed on the (1) potential of radiography, ultrasound, and magnetic resonance imaging to assess early tissue pathomechanics in OA, (2) relative utility of kinematic, structural, morphological, and biomechanical measures as functional imaging biomarkers, and (3) improved diagnostic specificity through the combination of multiple imaging biomarkers with unique contrasts, including elastography and quantitative assessments of tissue biochemistry. In comparison to other modalities, magnetic resonance imaging provides an extensive range of functional measures at the tissue level, with conventional and emerging techniques available to potentially to assess the spectrum of preclinical to advance OA.

Direct noninvasive measurement and numerical modeling of depth-dependent strains in layered agarose constructs.

Biomechanical factors play an important role in the growth, regulation, and maintenance of engineered biomaterials and tissues. While physical factors (e.g. applied mechanical strain) can accelerate regeneration, and knowledge of tissue properties often guide the design of custom materials with tailored functionality, the distribution of mechanical quantities (e.g. strain) throughout native and repair tissues is largely unknown. Here, we directly quantify distributions of strain using noninvasive magnetic resonance imaging (MRI) throughout layered agarose constructs, a model system for articular cartilage regeneration. Bulk mechanical testing, giving both instantaneous and equilibrium moduli, was incapable of differentiating between the layered constructs with defined amounts of 2% and 4% agarose. In contrast, MRI revealed complex distributions of strain, with strain transfer to softer (2%) agarose regions, resulting in amplified magnitudes. Comparative studies using finite element simulations and mixture (biphasic) theory confirmed strain distributions in the layered agarose. The results indicate that strain transfer to soft regions is possible in vivo as the biomaterial and tissue changes during regeneration and maturity. It is also possible to modulate locally the strain field that is applied to construct-embedded cells (e.g. chondrocytes) using stratified agarose constructs.

Noninvasive dualMRI-based strains vary by depth and region in human osteoarthritic articular cartilage.

OBJECTIVE: To noninvasively assay the mechanical and structural characteristics of articular cartilage from patients with osteoarthritis (OA) by magnetic resonance imaging (MRI), and to further relate spatial patterns of MRI-based mechanical strain to joint (depth-wise, regional) locations and disease severity. METHODS: Cylindrical osteochondral explants harvested from human tissue obtained during total knee replacement surgery were loaded in unconfined compression and 2D deformation data was acquired at 14.1 T using a displacements under applied loading by MRI (dualMRI) approach. After imaging, samples were histologically assessed for OA severity. Strains were determined by depth, and statistically analyzed for dependence on region in the joint and OA severity. RESULTS: Von Mises, axial, and transverse strains were highly depth-dependent. After accounting for other factors, Von Mises, axial, and shear strains varied significantly by region, with largest strain magnitudes observed in explants harvested from the tibial plateau and anterior condyle near exposed bone. Additionally, in all cases, strains in late-stage OA were significantly greater than either early- or mid-stage OA. Transverse strain in mid-stage OA explants, measured near the articular surface, was significantly higher than early-stage OA explants. CONCLUSION: dualMRI was demonstrated in human OA tissue to quantify the effects of depth, joint region, and OA severity, on strains resulting from mechanical compression. These data suggest dualMRI may possess a wide range of utility, such as validating computational models of soft tissue deformation, assaying changes in cartilage function over time, and perhaps, once implemented for cartilage imaging in vivo, as a new paradigm for diagnosis of early- to mid-stage OA.

Tribological altruism: A sacrificial layer mechanism of synovial joint lubrication in articular cartilage.

Boundary lubrication is characterized by sliding surfaces separated by a molecularly thin film that reduces friction and wear of the underlying substrate when fluid lubrication cannot be established. In this study, the wear and replenishment rates of articular cartilage were examined in the context of friction coefficient changes, protein loss, and direct imaging of the surface ultrastructure, to determine the efficiency of the boundary lubricant (BL) layer. Depletion of cartilage lubricity occurred with the concomitant loss of surface proteoglycans. Restoration of lubrication by incubation with synovial fluid was much faster than incubation with culture media and isolated superficial zone protein. The replenishment action of the BL layer in articular cartilage was rapid, with the rate of formation exceeding the rate of depletion of the BL layer to effectively protect the tissue from mechanical wear. The obtained results indicate that boundary lubrication in articular cartilage depends in part on a sacrificial layer mechanism. The present study provides insight into the natural mechanisms that minimize wear and resist tissue degeneration over the lifetime of an organism.

Mechanostasis in apoptosis and medicine.

Mechanostasis describes a complex and dynamic process where cells maintain equilibrium in response to mechanical forces. Normal physiological loading modes and magnitudes contribute to cell proliferation, tissue growth, differentiation and development. However, cell responses to abnormal forces include compensatory apoptotic mechanisms that may contribute to the development of tissue disease and pathological conditions. Mechanotransduction mechanisms tightly regulate the cell response through discrete signaling pathways. Here, we provide an overview of links between pro- and anti-apoptotic signaling and mechanotransduction signaling pathways, and identify potential clinical applications for treatments of disease by exploiting mechanically-linked apoptotic pathways.

The role of lubricant entrapment at biological interfaces: reduction of friction and adhesion in articular cartilage.

Friction and adhesion of articular cartilage from high- and low-load-bearing regions of bovine knee joints were examined with a tribometer under various loads and equilibration times. The effect of trapped lubricants was investigated by briefly unloading the cartilage sample before friction testing, to allow fluid to reflow into the contact interface and boundary lubricants to rearrange. Friction and adhesion of high-load-bearing joint regions were consistently lower than those of low-load-bearing regions. This investigation is the first to demonstrate the regional variation in the friction and adhesion properties of articular cartilage. Friction coefficient decreased with increasing contact pressure and decreasing equilibration time. Briefly unloading cartilage before the onset of sliding resulted in significantly lower friction and adhesion and a loss of the friction dependence on contact pressure, suggesting an enhancement of the cartilage tribological properties by trapped lubricants. The results of this study reveal significant differences in the friction and adhesion properties between high- and low-load-bearing joint regions and elucidate the role of trapped lubricants in cartilage tribology.

The superficial medial collateral ligament reconstruction of the knee: effect of altering graft length on knee kinematics and stability.

PURPOSE: The purpose of this study was to evaluate and compare the resulting knee kinematics and stability of an anatomic superficial MCL (sMCL) reconstruction and a non-anatomic sMCL reconstruction. METHODS: In a cadaveric model, normal knee stability and kinematics were compared with sMCL deficient knees and with two experimental sMCL reconstructions. The first reconstruction (AnatRecon) attempted to anatomically reconstruct the sMCL. The second reconstruction (ShortRecon) used a shorter graft to mimic the effect of failing to reproduce the anatomic length of the sMCL. Changes in position of the femur with respect to the tibia were measured with an electromagnetic tracking system during simulated active knee extension and during passive knee stability testing in the sMCL intact knee, the sMCL deficient knee, and the two experimental reconstructions. RESULTS: Simulated active knee extension demonstrated a significant increase in external tibial rotation of ShortRecon compared to AnatRecon between 30° and 80° of knee flexion (mean difference <3.0° over the range of knee flexion angles; P < 0.008), and a significant increase in external tibial rotation of ShortRecon compared to the intact sMCL was found at 60° and 70° of knee flexion (mean difference <2.0°over the range of knee flexion angles; P < 0.008). Passive joint stability testing demonstrated that division of the sMCL produced approximately 6° of valgus laxity at 30° of knee flexion and increased external tibial rotation of approximately 5° at 30°, 9° at 60°, and 10° at 90° of knee flexion, respectively. AnatRecon restored normal knee kinematics and stability. Additionally, passive stability testing demonstrated a significant increase in external tibial rotation of ShortRecon compared to AnatRecon at 60° (mean difference = 3.7°; P < 0.05) and 90° of knee flexion (mean difference = 4.9°; P < 0.05). CONCLUSION: Anatomic reconstruction of the sMCL effectively restored knee kinematics and stability in the sMCL deficient knee. Altering the normal ligament length resulted in measurable changes in knee kinematics and stability. This study suggests that in cases of chronic valgus knee instability, anatomic sMCL reconstruction would provide better results than non-anatomic sMCL reconstruction.

Polymer Mechanics as a Model for Short-Term and Flow-Independent Cartilage Viscoelasticity.

Articular cartilage is the load bearing soft tissue that covers the contacting surfaces of long bones in articulating joints. Healthy cartilage allows for smooth joint motion, while damaged cartilage prohibits normal function in debilitating joint diseases such as osteoarthritis. Knowledge of cartilage mechanical function through the progression of osteoarthritis, and in response to innovative regeneration treatments, requires a comprehensive understanding of the molecular nature of interacting extracellular matrix constituents and interstitial fluid. The objectives of this study were therefore to (1) examine the timescale of cartilage stress-relaxation using different mechanistic models and (2) develop and apply a novel (termed "sticky") polymer mechanics model to cartilage stress-relaxation based on temporary binding of constituent macromolecules. Using data from calf cartilage samples, we found that different models captured distinct timescales of cartilage stress-relaxation: monodisperse polymer reptation best described the first second of relaxation, sticky polymer mechanics best described data from ∼1-100 seconds of relaxation, and a model of inviscid fluid flow through a porous elastic matrix best described data from 100 seconds to equilibrium. Further support for the sticky polymer model was observed using experimental data where cartilage stress-relaxation was measured in either low or high salt concentration. These data suggest that a complete understanding of cartilage mechanics, especially in the short time scales immediately following loading, requires appreciation of both fluid flow and the polymeric behavior of the extracellular matrix.

Dependence of nanoscale friction and adhesion properties of articular cartilage on contact load.

Boundary lubrication of articular cartilage by conformal, molecularly thin films reduces friction and adhesion between asperities at the cartilage-cartilage contact interface when the contact conditions are not conducive to fluid film lubrication. In this study, the nanoscale friction and adhesion properties of articular cartilage from typical load-bearing and non-load-bearing joint regions were studied in the boundary lubrication regime under a range of physiological contact pressures using an atomic force microscope (AFM). Adhesion of load-bearing cartilage was found to be much lower than that of non-load-bearing cartilage. In addition, load-bearing cartilage demonstrated steady and low friction coefficient through the entire load range examined, whereas non-load-bearing cartilage showed higher friction coefficient that decreased nonlinearly with increasing normal load. AFM imaging and roughness calculations indicated that the above trends in the nanotribological properties of cartilage are not due to topographical (roughness) differences. However, immunohistochemistry revealed consistently higher surface concentration of boundary lubricant at load-bearing joint regions. The results of this study suggest that under contact conditions leading to joint starvation from fluid lubrication, the higher content of boundary lubricant at load-bearing cartilage sites preserves synovial joint function by minimizing adhesion and wear at asperity microcontacts, which are precursors for tissue degeneration.

Increased friction coefficient and superficial zone protein expression in patients with advanced osteoarthritis.

OBJECTIVE: To quantify the concentration of superficial zone protein (SZP) in the articular cartilage and synovial fluid of patients with advanced osteoarthritis (OA) and to further correlate the SZP content with the friction coefficient, OA severity, and levels of proinflammatory cytokines. METHODS: Samples of articular cartilage and synovial fluid were obtained from patients undergoing elective total knee replacement surgery. Additional normal samples were obtained from donated body program and tissue bank sources. Regional SZP expression in cartilage obtained from the femoral condyles was quantified by enzyme-linked immunosorbent assay (ELISA) and visualized by immunohistochemistry. Friction coefficient measurements of cartilage plugs slid in the boundary lubrication system were obtained. OA severity was graded using histochemical analyses. The concentrations of SZP and proinflammatory cytokines in synovial fluid were determined by ELISA. RESULTS: A pattern of SZP localization in knee cartilage was identified, with load-bearing regions exhibiting high SZP expression. SZP expression patterns were correlated with friction coefficient and OA severity; however, SZP expression was observed in all samples at the articular surface, regardless of OA severity. SZP expression and aspirate volume of synovial fluid were higher in OA patients than in normal controls. Expression of cytokines was elevated in the synovial fluid of some patients. CONCLUSION: Our findings indicate a mechanochemical coupling in which physical forces regulate OA severity and joint lubrication. The findings of this study also suggest that SZP may be ineffective in reducing joint friction in the boundary lubrication mode at an advanced stage of OA, where other mechanisms may dominate the observed tribological behavior.

A biomechanical comparison of the Surgical Implant Generation Network (SIGN) tibial nail with the standard hollow nail.

OBJECTIVE: In developing countries, tibial shaft fractures are frequently stabilised using Surgical Implant Generation Network (SIGN) nails. Despite widespread use throughout the world, little is known regarding their biomechanical properties. This study aimed to compare the mechanical stiffness of the SIGN tibial nail with a standard hollow tibial nail. METHODS: A fracture gap model was created to simulate a comminuted mid-shaft tibia fracture (AO/OTA42-C3) using synthetic composite bones. The constructs were stabilised with either a 9 mm solid SIGN nail or a 10 mm hollow Russell-Taylor nail. Both nail systems were interlocked proximally and distally. Following fixation, the specimens were loaded in axial, torsional, and cyclical axial modes to calculate construct stiffness and irreversible (plastic) deformation. RESULTS: The mean axial stiffness for the SIGN nail constructs was 47% higher than mean stiffness for the RT nail constructs (p<0.001). The difference in torsional stiffness was not statistically significant. However, the SIGN group demonstrated 159% more irreversible deformation than the Russell-Taylor group (p=0.006) for the loading parameters studied. CONCLUSION: The SIGN tibial nail, despite its slightly smaller diameter, can provide similar construct stiffness and stability, when compared to a larger hollow nail for stabilisation of tibial shaft fractures.

Atomic force microscope investigation of the boundary-lubricant layer in articular cartilage.

OBJECTIVE: To determine the roles of superficial zone protein (SZP), hyaluronan (HA), and surface-active phospholipids (SAPL) in boundary lubrication of articular cartilage through systematic enzyme digestion using trypsin, hyaluronidase, and phospolipase-C (PLC) surface treatments. METHODS: The friction coefficient of articular cartilage surfaces was measured with an atomic force microscope (AFM) before and after enzyme digestion. Surface roughness, adhesion, and stiffness of the articular surface were also measured to determine the mechanism of friction in the boundary lubrication regime. Histology and transmission electron microscopy were used to visualize the surface changes of treatment groups that showed significant friction changes after enzyme digestion. RESULTS: A significant increase in the friction coefficient of both load-bearing and non load-bearing regions of the joint was observed after proteolysis by trypsin. Treatment with trypsin, hyaluronidase, or PLC did not affect the surface roughness. However, trypsin treatment decreased the adhesion significantly. Results indicate that the protein component at the articular cartilage surface is the main boundary lubricant, with SZP being a primary candidate. The prevailing nanoscale deformation processes are likely plastic and/or viscoelastic in nature, suggesting that plowing is the dominant friction mechanism. CONCLUSIONS: The findings of this study indicate that SZP plays an intrinsic and critical role in boundary lubrication at the articular surface of cartilage, whereas the effects of HA and SAPL on the tribological behavior are marginal.