A systematic review on the potential value of synovial fluid biomarkers to predict clinical outcomes in cartilage repair treatments.

OBJECTIVE: Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including osteoarthritis (OA). Synovial fluid (SF) biomarker measurement is a potential method to predict treatment response and effectiveness. However, the significance of different biomarkers and their correlation to clinical outcomes remains unclear. This systematic review evaluated current SF biomarkers used in investigation of cartilage degeneration or regeneration in the knee joint and correlated these biomarkers with clinical outcomes following cartilage repair or regeneration interventions. METHOD: PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. Studies evaluating SF biomarkers and clinical outcomes following cartilage repair intervention were included. Two researchers independently performed data extraction and Quality Assessment of Diagnostic Accuracy Score 2 (QUADAS-2) analysis. Biomarker inclusion, change following intervention and correlation with clinical outcome was compared. RESULTS: 9 studies were included. Study heterogeneity precluded meta-analysis. There was significant variation in sampling and analysis. 33 biomarkers were evaluated in addition to microRNA and catabolic/anabolic ratios. Five studies reported on correlation of biomarkers with six biomarkers significantly correlated with clinical outcomes following intervention. However, correlation was only demonstrated in isolated studies. CONCLUSION: This review demonstrates significant difficulties in drawing conclusions regarding the importance of SF biomarkers based on the available literature. Improved standardisation for collection and analysis of SF samples is required. Future publications should also focus on clinical outcome scores and seek to correlate biomarkers with progression to further understand the significance of identified markers in a clinical context. REGISTRATION NUMBER: PROSPERO CRD42022304298. Study protocol available on PROSPERO website.

Skin-Driven Ultrasensitive Mechanoluminescence Sensor Inspired by Spider Leg Joint Slits.

Inspired by the spider's slit organ embedded in the leg joint exoskeleton and its ultrasensitive stress perception, we propose to fix the conflict between the stress concentration requirement for bright mechanoluminescence (ML) and the stress dispersion effect of soft material via integrating slit microstructures into flexible films. The designed slits focus weak stresses onto the corner to achieve high sensitivity, leading to 10-30 times ML intensity improvement at weak strain (<10% stretch) application. Slit morphology and various patterns were well investigated to address the stress distribution regularity. The slit-based ML film offers a facile light-luminescent artificial skin for visualizable stress presentations or detections without electricity power source. It is a practical endeavor of photonic skin for visible vocalization and a significant contribution to dysaudia auxiliary or luminescence augmented expressions for human social interactions, similar to jellyfish or squids.

Factors Affecting the Aluminum, Arsenic, Cadmium and Lead Concentrations in the Knee Joint Structures.

Background: Toxic elements, such as aluminum (Al), arsenic (As), cadmium (Cd), and lead (Pb), are persistent environmental pollutants that can cause adverse effects on the health of exposed individuals. Bone is one of the primary target organs of accumulation and potential damage from toxic elements. Objectives: This study was performed to determine the Al, As, Cd, and Pb concentrations in the femoral cancellous bone, femoral cartilage, anterior cruciate ligament, meniscus, tibial cartilage, tibial cancellous bone and infrapatellar fat pad. Furthermore, the aim of this study was to explore the relationships between toxic element concentrations and related factors such as gender, age, place of residence, hypertension and diabetes, and to determine the correlations among these toxic elements in knee joint structures. Methods: The samples used this study were collected from 51 patients following total knee arthroplasty. The Al, As, Cd, and Pb concentrations were determined using inductively coupled plasma optic emission spectrometry. Results: Significant differences were found in the Al, As, Cd, and Pb concentrations among the knee joint structures. Cd concentration in the tibial cancellous bone in women was significantly higher than in men. Pb concentration in the infrapatellar fat pad of urban patients was significantly higher as compared to rural patients. Al concentrations in the femoral cancellous bone, femoral cartilage, anterior cruciate ligament, meniscus and tibial cartilage were significantly higher in patients living in urban areas than in rural areas. As concentration in the tibial cancellous bone of diabetic patients was significantly higher compared to non-diabetic patients. In addition, significant Spearman's positive correlations were found between Al and Pb in the knee joint structures. Conclusion: The obtained results of the investigated toxic elements may serve as a basis for establishing the reference values of Al, As, Cd, and Pb in the knee joint structures. The results reported in the study provides novel data regarding the relationships between the toxic element concentrations and gender, age, place of residence, hypertension and diabetes in the studied structures of knee joint. Furthermore, new interactions among these toxic elements were noted.

Immediate, short and medium-term effects of orthopedic insoles with a metatarsal retro-capital bar on biomechanical variables, plantar pressures and muscle activity in running.

BACKGROUND: The aim of this study was to evaluate the effect of 12 weeks of use of orthopedic insoles equipped with a metatarsal retro-capital bar (MRCB) on plantar pressure under the feet and lower limb kinematic variables during running. METHODS: Two groups of 10 runners used for 12 weeks while running orthopedic insoles without correction or equipped with a MRCB. All participants performed successively a standing posture (CoP displacement) test and a running test at 11 km.h-1 (lower limb kinematic variables) using with flat insoles and orthopedic neutral or MRCB insoles at the beginning (T0), after 4 (T4) and 12 weeks (T12) of use. RESULTS: For the MRCB group, CoP moved backwards while forefoot plantar pressure was decreased during standing position at T4 and T12 compared to T0. During running, the plantar pressure under the 2nd, 3rd and 4th metatarsal heads was reduced with MRCB at T0, T4 and T12. The one under the 1st metatarsal head was decreased at T4 and T12, when MRCB or flat insoles were used. The maximal extension and the total amplitude of ankle were slightly increased at T4 and T12 with or without wearing MRCB insoles. Similar changes in knee joint kinematics were observed but only at T12. Any significant changes were found in runners that used orthopedic insoles without correction. CONCLUSIONS: Orthopedic insoles equipped with MRCB involve lower plantar pressure under the metatarsal heads, which may be of interest to treat forefoot injuries in runners.

Impact of Varied Factors on Iron, Nickel, Molybdenum and Vanadium Concentrations in the Knee Joint.

The aim of this study was to determine the concentrations of iron, nickel, molybdenum, and vanadium in the knee joint. We also examined the relationships between the concentrations of these metals in the knee joint and the influence of varied factors on the concentration of Fe, Ni, Mo, and V. The study of these trace elements is important, because these elements are used alone and in combination in diet supplements, and they are components of biomaterials implanted in medicine. The study materials, consisting of the spongy bone, cartilage, meniscus, anterior cruciate ligament (ACL), and infrapatellar fat pad, were obtained from 34 women and 12 men from northwestern Poland. The concentrations of Ni, Fe, Mo, and V were determined using spectrophotometric atomic absorption in inductively coupled argon plasma (ICP-AES). We found significantly higher Mo concentrations in the ACL of women than men. There was a significant difference in the Mo concentration in the spongy bone between patients from cities with fewer than 100,000 inhabitants and patients from cities with more than 100,000 residents. Iron concentrations in the spongy bone were higher in non-smoking patients and those who did not consume alcohol. Vanadium concentrations were higher in the infrapatellar fat pads in abstainers. In patients who had not undergone arthroscopy surgery, V concentration was lower in cartilage. The concentrations of V in the cartilage and infrapatellar fat pad were higher in osteoporotic patients than in non-osteoporotic patients. There were significant differences in Fe concentrations in the meniscus, with the lowest in osteoporotic patients. We noted lower Mo concentrations in the spongy bone of patients with rheumatoid arthritis. Furthermore, we noted some new interactions among metals in the studied structures of the knee joint. The results reported in this study show the influence of gender, place of residence, smoking, consumption of alcohol, arthroscopy surgery, osteoporosis, and rheumatoid arthritis on the Fe, Ni, Mo, and V concentrations in the studied structures of the knee joint.

Laboratory-based versus qualitative assessment of α-defensin in periprosthetic hip and knee infections: a systematic review and meta-analysis.

INTRODUCTION: Two methods are currently available for the assay of α-defensin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test. We aimed to assess the diagnostic accuracy of synovial fluid α-defensin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection. MATERIALS AND METHODS: We searched (from inception to May 2018) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on α-defensin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed using the bivariate diagnostic random-effects model. The receiver-operating curve for each method was calculated. RESULTS: We included 13 articles in our meta-analysis, including 1170 patients who underwent total hip and knee arthroplasties revision; 368 (31%) had a joint infection according to MSIS and MSIS-modified criteria. Considering the false-positive result rate of 8% and false-negative result rate of 3%, pooled sensitivity and specificity were 0.90 (95% CI 0.83-0.94) and 0.95 (0.92-0.96), respectively. The area under the curve (AUC) was 0.94 (0.92-0.94). No statistical differences in terms of sensitivity and specificity were found between the laboratory-based and qualitative test. The pooled sensitivity and specificity of the two alpha-defensin assessment methods were: laboratory-based test 0.97 (95% CI 0.93-0.99) and 0.96 (95% CI 0.94-0.98), respectively; qualitative test 0.83 (95% CI 0.73-0.91) and 0.94 (95% CI 0.89-0.97), respectively. The diagnostic odds ratio of the α-defensin laboratory based was superior to that of the qualitative test (1126.085, 95% CI 352.172-3600.702 versus 100.9, 95% CI 30.1-338.41; p < 0.001). The AUC for immunoassay and qualitative tests was 0.97 (0.95-0.99) and 0.91 (0.88-0.99), respectively. CONCLUSION: Detection of α-defensin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two alpha-defensin assessment methods is comparable. The lateral flow assay is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.

Ultraviolet light (365 nm) transmission properties of articular cartilage as a function of depth, extracellular matrix, and swelling.

Current tissue engineering approaches for treatment of injured or diseased articular cartilage use ultraviolet light (UV) for in situ photopolymerization of biomaterials to fill chondral and osteochondral defects as well as resurfacing, stiffening and bonding the extracellular matrix and tissue interfaces. The most commonly used UV light wavelength is UVA 365 nm, the least cytotoxic and deepest penetrating. However, little information is available on the transmission of UVA 365 nm light through the cartilage matrix. In the present study, 365 nm UV light transmission was measured as a function of depth through 100 µm thick slices of healthy articular cartilage removed from mature bovine knees. Transmission properties were measured in normal (Native) cartilage and after swelling equilibration in phosphate-buffered saline (Swollen). Single-factor and multiple linear regression analyses were performed to determine depth-dependencies between the effective attenuation coefficients and proteoglycan, collagen and water contents. For both cartilages, a significant depth-dependency was found for the effective attenuation coefficients, being highest at the articular surface (superficial zone) and decreasing with depth. The effective attenuation coefficients for full-thickness cartilages were approximately a third lower than the total attenuation coefficients calculated from the individual slices. Analysis of absorption and scattering effects due to the ECM and chondrocytes found that UV light scatter coefficients were ∼10 times greater than absorption coefficients. The greater transmittance of UV light through the thicker cartilage was attributed to the collagen within the ECM causing significant backscatter forward reflectance.

Concurrent validity of lower extremity kinematics and jump characteristics captured in pre-school children by a markerless 3D motion capture system.

Background: Investigations into the possible associations between early in life motor function and later in life musculoskeletal health, will require easily obtainable, valid, and reliable measures of gross motor function and kinematics. Marker-based motion capture systems provide reasonably valid and reliable measures, but recordings are restricted to expensive lab environments. Markerless motion capture systems can provide measures of gross motor function and kinematics outside of lab environments and with minimal interference to the subjects being investigated. It is, however, unknown if these measures are sufficiently valid and reliable in young children to warrant further use. This study aims to document the concurrent validity of a markerless motion capture system: "The Captury." Method: Measures of gross motor function and lower extremity kinematics from 14 preschool children (age between three and 6 years) performing a series of squats and standing broad jumps were recorded by a marker-based (Vicon) and a markerless (The Captury) motion capture system simultaneously, in December 2015. Measurement differences between the two systems were examined for the following variables: jump length, jump height, hip flexion, knee flexion, ankle dorsi flexion, knee varus, knee to hip separation distance ratio (KHR), ankle to hip separation distance ratio (AHR), frontal plane projection angle, frontal plane knee angle (FPKA), and frontal plane knee deviation (FPKD). Measurement differences between the systems were expressed in terms of root mean square errors, mean differences, limits of agreement (LOA), and intraclass correlations of absolute agreement (ICC (2,1) A) and consistency of agreement. Results: Measurement differences between the two systems varied depending on the variables. Agreement and reliability ranged from acceptable for e.g. jump height [LOA: - 3.8 cm to 2.2 cm; ICC (2,1) A: 0.91] to unacceptable for knee varus [LOA: - 33° to 19°; ICC (2,1) A: 0.29]. Conclusions: The measurements by the markerless motion capture system "The Captury" cannot be considered interchangeable with the Vicon measures, but our results suggest that this system can produce estimates of jump length, jump height, KHR, AHR, knee flexion, FPKA, and FPKD, with acceptable levels of agreement and reliability. These variables are promising for use in future research but require further investigation of their clinimetric properties.

The Amphoteric and Hydrophilic Properties of Cartilage Surface in Mammalian Joints: Interfacial Tension and Molecular Dynamics Simulation Studies.

In this paper, we explain the amphoteric character of the cartilage surface by studying a lipid bilayer model built from phospholipids. We examined the interfacial tension values and molecular dynamics simulation in solutions of varying pH. The effects of negative and positive charge density (or fixed charges) on the (cartilage/cartilage) friction coefficient were investigated. In physiological (or synovial) fluid, after the isoelectric point (pI), the curve of interfacial tension decreases rapidly as it reaches pH 7.4 and then approaches a constant value at higher pH. It was shown that the curve of the interfacial tension curve exhibits a maximum value at the isoelectric point with a Gaussian shape feature. The phospholipid bilayers facilitate an almost frictionless contact in the joint. Moreover, the slippage of the bilayer and the short-range repulsion between the surfaces of the negatively charged cartilage surfaces are the main determinants of the low frictional properties of the joint.

Evaluation of the torque-angular velocity relationship across various joint positions.

BACKGROUND: Standard neuromuscular assessment through a single value, such as the maximum voluntary torque, could be limited since it changes substantially with movement velocity and joint position and could not discern among force, velocity or power producing capacities of a specific muscle. Therefore, we aimed to evaluate the torque-angular velocity (T-AV) interchange across various joint positions. METHODS: Knee extensors were tested in 40 physically active participants at six velocities between 30° and 180°/s. Both, linear and the second-order polynomial regression methods were applied on peak torque (TMAX) and angle specific torque outputs (between 80° to 20° of knee extension). RESULTS: The obtained results suggest decline of the concentric torque as angular velocity increases (P<0.05). The obtained the T-AV relationship appears to be strong and linear for the most subjects (R2=0.74-0.97) and highly reliable (r>0.80) at least when the positions around the TMAX angle are considered. CONCLUSIONS: The present study revealed that the T-AV relationship of knee extensors, observed from isokinetic tests conducted within a wide range of angular velocities, could be strong, linear and reliable. The results demonstrate that linear regression method could be feasible approach for evaluating individual muscle mechanical capacities.

A unique anisotropic R2 of collagen degeneration (ARCADE) mapping as an efficient alternative to composite relaxation metric (R2 -R1ρ ) in human knee cartilage study.

PURPOSE: Anisotropic transverse R2 (1/T2 ) relaxation of water proton is sensitive to cartilage degenerative changes. The purpose is to develop an efficient method to extract this relaxation metric in clinical studies. METHODS: Anisotropic R2 can be measured inefficiently by standard R2 mapping after removing an isotropic contribution obtained from R1ρ mapping. In the proposed method, named as a unique anisotropic R2 of collagen degeneration (ARCADE) mapping, an assumed uniform isotropic R2 was estimated at magic angle locations in the deep cartilage, and an anisotropic R2 was thus isolated in a single T2W sagittal image. Five human knees from 4 volunteers were studied with standard R2 and R1ρ mappings at 3T, and anisotropic R2 derived from ARCADE on the T2W (TE = 48.8 ms) image from R2 mapping was compared with the composite relaxation (R2 - R1ρ ) using statistical analysis including Student's t-test and Pearson's correlation coefficient. RESULTS: Anisotropic R2 (1/s) from ARCADE was highly positively correlated with but not significantly different from standard R2 - R1ρ (1/s) in the segmented deep (r = 0.83 ± 0.06; 8.3 ± 2.9 vs. 7.3 ± 1.9, P = .50) and the superficial (r = 0.82 ± 0.05; 3.5 ± 2.4 vs. 4.5 ± 1.6, P = .39) zones. However, after eliminating systematic errors by the normalization in terms of zonal contrast, anisotropic R2 was significantly higher (60.2 ± 18.5% vs. 38.4 ± 16.6%, P < .01) than R2 - R1ρ as predicted. CONCLUSION: The proposed anisotropic R2 mapping could be an efficient alternative to the conventional approach, holding great promise in providing both high-resolution morphological and more sensitive transverse relaxation imaging from a single T2W scan in a clinical setting.

Phosphorus Concentration in Knee Joint Structures of Patients Following Replacement Surgery.

The aim of the study was to assess phosphorus (P) concentration in structures of the knee joint-including the tibial spongy bone, articular cartilage, meniscus, anterior cruciate ligament, and infrapatellar fat pad (Hoffa's fat pad)-of patients following knee joint replacement. The study also aimed to assess the influence of selected biological and environmental factors on P concentration in studied parts of the knee joint. Phosphorus concentration was determined using inductively coupled plasma-atomic emission spectrometry (ICP-AES). Statistically significant differences in P concentration were found between different elements of the knee joint. The highest P concentration was measured in the spongy bone (72,746.68 mg kg-1 dw) and the lowest in the Hoffa's fat pad (1203.19 mg kg-1 dw). P levels were unaffected by gender, age, BMI, place of residence, smoking, or alcohol consumption. Data on P concentration in the osteoarticular elements of the knee may be useful in the interpretation and evaluation of biochemical, morphological, and mechanical changes occurring in the body.

Immunohistochemical examination in arthrofibrosis of the knee joint.

INTRODUCTION: Arthrofibrosis (AF) is the result of increased cell proliferation and synthesis of matrix proteins (collagen I, III, and VI). Especially after invasive knee surgery, e.g., ligament reconstruction or knee replacement, abnormal fibroblast proliferation with pathological periarticular fibrosis can be observed leading to severely limited joint motion. The pathogenesis of AF is currently not fully understood. The present work aims to determine pathogenic factors. MATERIALS AND METHODS: A descriptive, histological and immunohistochemical comparative study was performed on tissue samples of 14 consecutive patients undergoing arthrolysis for joint stiffness due to AF. Seven human autopsy specimens served as control. Samples were stained for expression of relevant markers such as CD68, α-smooth muscle actin (ASMA), beta-catenin, BMP-2 and examined for the histological grade of AF (cell-rich versus cell-poor) and compared to a control. Furthermore, a microscopic evaluation of the samples for cell differentiation and number was performed. RESULTS: Tissue sections of cell-rich fibrosis showed a significantly higher expression of CD68 compared to the control with less than 10% of CD68 positive cells (p = 0.002). In cell-poor fibrosis no statistically significant difference was obvious (p = 0.228). Expression of ASMA in synovia, vessels, cell-rich and cell-poor fibrosis showed median values of 2.00 in the AF group and 1.75 in the control. Both groups differed significantly (p = 0.003). AF tissue showed a significantly difference in expression of ß-catenin (p < 0.001) compared to the control. The overall difference between AF and control group in expression of BMP-2 was also statistically significant (p = 0.002). CONCLUSIONS: Expression of CD68, ASMA, beta-catenin and BMP-2 is significantly increased in AF tissue samples. Based on presented findings, histological evaluation and immunohistochemical assessment of CD68, ASMA, ß-catenin and BMP-2 expression may proof useful to diagnose AF and to analyze AF activity.

The evolving large-strain shear responses of progressively osteoarthritic human cartilage.

OBJECTIVE: The composition and structure of articular cartilage evolves during the development and progression of osteoarthritis (OA) resulting in changing mechanical responses. We aimed to assess the evolution of the intrinsic, large-strain mechanics of human articular cartilage-governed by collagen and proteoglycan and their interactions-during the progression of OA. DESIGN: We completed quasi-static, large-strain shear tests on 64 specimens from ten donors undergoing total knee arthroplasty (TKA), and quantified the corresponding state of OA (OARSI grade), structural integrity (PLM score), and composition (glycosaminoglycan and collagen content). RESULTS: We observed nonlinear stress-strain relationships with distinct hystereses for all magnitudes of applied strain where stiffnesses, nonlinearities, and hystereses all reduced as OA advanced. We found a reduction in energy dissipation density up to 80% in severely degenerated (OARSI grade 4, OA-4) vs normal (OA-1) cartilage, and more importantly, we found that even cartilage with a normal appearance in structure and composition (OA-1) dissipated 50% less energy than healthy (control) load-bearing cartilage (HL0). Changes in stresses and stiffnesses were in general less pronounced and did not allow us to distinguish between healthy load-bearing controls and very early-stage OA (OA-1), or to distinguish consistently among different levels of degeneration, i.e., OARSI grades. CONCLUSIONS: Our results suggest that reductions in energy dissipation density can be detected by bulk-tissue testing, and that these reductions precede visible signs of degeneration. We highlight the potential of energy dissipation, as opposed to stress- or stiffness-based measures, as a marker to diagnose early-stage OA.

Metabolite assignment of ultrafiltered synovial fluid extracted from knee joints of reactive arthritis patients using high resolution NMR spectroscopy.

Currently, there are no reliable biomarkers available that can aid early differential diagnosis of reactive arthritis (ReA) from other inflammatory joint diseases. Metabolic profiling of synovial fluid (SF)-obtained from joints affected in ReA-holds great promise in this regard and will further aid monitoring treatment and improving our understanding about disease mechanism. As a first step in this direction, we report here the metabolite specific assignment of 1 H and 13 C resonances detected in the NMR spectra of SF samples extracted from human patients with established ReA. The metabolite characterization has been carried out on both normal and ultrafiltered (deproteinized) SF samples of eight ReA patients (n = 8) using high-resolution (800 MHz) 1 H and 1 H─13 C NMR spectroscopy methods such as one-dimensional 1 H CPMG and two-dimensional J-resolved1 H NMR and homonuclear 1 H─1 H TOCSY and heteronuclear1 H─13 C HSQC correlation spectra. Compared with normal SF samples, several distinctive 1 H NMR signals were identified and assigned to metabolites in the 1 H NMR spectra of ultrafiltered SF samples. Overall, we assigned 53 metabolites in normal filtered SF and 64 metabolites in filtered pooled SF sample compared with nonfiltered SF samples for which only 48 metabolites (including lipid/membrane metabolites as well) have been identified. The established NMR characterization of SF metabolites will serve to guide future metabolomics studies aiming to identify/evaluate the SF-based metabolic biomarkers of diagnostic/prognostic potential or seeking biochemical insights into disease mechanisms in a clinical perspective.

Gait Mechanics and T1ρ MRI of Tibiofemoral Cartilage 6 Months after ACL Reconstruction.

PURPOSE: Aberrant walking biomechanics after anterior cruciate ligament reconstruction (ACLR) are hypothesized to be associated with deleterious changes in knee cartilage. T1ρ magnetic resonance imaging (MRI) is sensitive to decreased proteoglycan density of cartilage. Our purpose was to determine associations between T1ρ MRI interlimb ratios (ILR) and walking biomechanics 6 months after ACLR. METHODS: Walking biomechanics (peak vertical ground reaction force (vGRF), vGRF loading rate, knee extension moment, knee abduction moment) were extracted from the first 50% of stance phase in 29 individuals with unilateral ACLR. T1ρ MRI ILR (ACLR limb/uninjured limb) was calculated for regions of interest in both medial and lateral femoral (LFC) and medial and lateral tibial condyles. Separate, stepwise linear regressions were used to determine associations between biomechanical outcomes and T1ρ MRI ILR after accounting for walking speed and meniscal/chondral injury (P ≤ 0.05). RESULTS: Lesser peak vGRF in the ACLR limb was associated with greater T1ρ MRI ILR for the LFC (posterior ΔR = 0.14, P = 0.05; central ΔR = 0.15, P = 0.05) and medial femoral condyle (central ΔR = 0.24, P = 0.01). Lesser peak vGRF loading rate in the ACLR limb (ΔR = 0.21, P = 0.02) and the uninjured limb (ΔR = 0.27, P = 0.01) was associated with greater T1ρ MRI ILR for the anterior LFC. Lesser knee abduction moment for the injured limb was associated with greater T1ρ MRI ILR for the anterior LFC (ΔR = 0.16, P = 0.04) as well as the posterior medial tibial condyle (ΔR = 0.13, P = 0.04). CONCLUSION: Associations between outcomes related to lesser mechanical loading during walking and greater T1ρ MRI ILR were found 6 months after ACLR. Although preliminary, our results suggest that underloading of the ACLR limb at 6 months after ACLR may be associated with lesser proteoglycan density in the ACLR limb compared with the uninjured limb.

Selective Enzymatic Digestion of Proteoglycans and Collagens Alters Cartilage T1rho and T2 Relaxation Times.

Our objective was to determine the relationship of T1rho and T2 relaxation mapping to the biochemical and biomechanical properties of articular cartilage through selective digestion of proteoglycans and collagens. Femoral condyles were harvested from porcine knee joints and treated with either chondroitinase ABC (cABC) followed by collagenase, or collagenase followed by cABC. Magnetic resonance images were acquired and cartilage explants were harvested for biochemical, biomechanical, and histological analyses before and after each digestion. Targeted enzymatic digestion of proteoglycans with cABC resulted in elevated T1rho relaxation times and decreased sulfated glycosaminoglycan content without affecting T2 relaxation times. In contrast, extractable collagen and T2 relaxation times were increased by collagenase digestion; however, neither was altered by cABC digestion. Aggregate modulus decreased with digestion of both components. Overall, we found that targeted digestion of proteoglycans and collagens had varying effects on biochemical, biomechanical, and imaging properties. T2 relaxation times were altered with changes in extractable collagen, but not changes in proteoglycan. However, T1rho relaxation times were altered with proteoglycan loss, which may also coincide with collagen disruption. Since it is unclear which matrix components are disrupted first in osteoarthritis, both markers may be important for tracking disease progression.

Is Soft Tissue Laxity Associated with Tissue Metal Concentrations after Total Knee Arthroplasty?

Increased joint laxity is associated with excessive polyethylene wear, but the correlation between laxity and metal wear has not been established. Fifteen necropsy-retrieved primary total knee replacements were mounted into a custom knee-testing machine that measured anterior-posterior, varus-valgus, and internal-external rotational laxity at 0°, 30°, 60°, and 90° of flexion. Inductively coupled plasma-mass spectrometry analysis was performed to measure the cobalt (Co), chromium (Cr), and titanium (Ti) concentrations in periprosthetic tissue samples. Spearman's rank correlations were performed to determine whether a significant correlation (p < 0.05) existed between soft tissue laxity and tissue metal concentrations. At 0° flexion, decreased posterior displacement was negatively correlated with elevated Co and Cr concentrations. At 30° flexion, decreased external rotation and varus deflection was negatively correlated with elevated Ti concentrations. At 60° flexion, decreased anterior displacement was negatively correlated with elevated Cr concentrations and decreased varus deflection was negatively correlated with increased Ti concentrations. At 90° flexion, decreased anterior displacement was negatively correlated with elevated Co and Cr concentrations. To our knowledge, this is the first study to investigate the correlation between tissue metal concentration and laxity. Decreased laxity was associated with elevated metal concentrations in periprosthetic tissue.

Study of chromium species release from metal implants in blood and joint effusion: Utilization of HPLC-ICP-MS.

The objective of this study was to develop and validate a novel analytical procedure for determination of total chromium and Cr(III) and Cr(VI) species released from metal implants into whole blood and joint effusion. Firstly, the ion-pair chromatographic method employing reversed-phase high-performance liquid chromatography inductively coupled plasma mass spectrometry (ICP-MS) for analysis of species was developed. Secondly, all samples, protein and low molecular fractions were analyzed for their total chromium content using ICP-MS. This new measurement procedure was validated by the following parameters: limit of detection (0.13 µg L-1 for Cr(III), 0.14 µg L-1 for Cr(VI)), linearity of calibration, trueness (recovery 84-92%), intermediate precision (RSD < 5%). We determined statistically significantly higher chromium levels in joint effusion samples obtained from patients in comparison with a control group. On the other hand, no relevant difference among the concentrations of both species and total chromium in blood was observed. Our results show that the majority of chromium is present in the trivalent form and bound to proteins. This speciation study is rare in the field of speciation analysis in clinical samples. It is characterized by very fast and simple sample preparation without any changes in distribution or stability of both Cr forms and efficient simultaneous analysis of Cr species.