Evaluation of Mechanically-Assisted Crevice Corrosion of Different Modular Dual Mobility Constructs.

BACKGROUND: Modular dual mobility (MDM) acetabular component use is rising in total hip arthroplasty. However, concern of mechanically assisted crevice corrosion (MACC) at the shell-liner interface remains. We investigated shell-liner corrosion using retrieval analyses and corrosion chamber testing. METHODS: We analyzed fretting and corrosion on 10 matched pairs of 2 commercial MDM constructs (MDM1 and MDM2). Also, pristine pairs of Ti6Al4V shells and CoCrMo liners from 3 commercial dual mobility systems (MDM1, MDM2, and MDM3) were tested in vitro to model MACC performance. Three pairs of each were placed into an electrochemical chamber with stepwise increasing cyclic compression loads while measuring currents generated at the shell-liner taper. Onset fretting loads and fretting currents were calculated. RESULTS: Corrosion damage scores on retrieved components were low but higher in the MDM2 to MDM1 liners (P = .006), specifically outside the taper region (P = .00003). Fretting currents were higher in the MDM2 than in MDM1 or MDM3 (P = .011). Onset loads were also higher in the MDM2 (P = .001). CONCLUSION: Among retrieved liners, MDM2 tapers seem prone to non-mechanical corrosion modes. Higher onset loads and fretting currents in MDM2 tapers indicate greater MACC resistance but higher severity once corrosion begins. Differences among the devices were likely due to taper design and surface finish. Currents in all 3 were <5 µA, much lower than those observed with head-neck tapers. Our findings suggest that, among the types of corrosion observed in these MDM designs, mechanically driven corrosion may not be the most significant.

Meta-analysis reveals differential gene expression in tetralogy of Fallot versus controls.

OBJECTIVES: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect in the United States. We aimed to identify genetic variations associated with TOF using meta-analysis of publicly available digital samples to spotlight targets for prevention, screening, and treatment strategies. METHODS: We used the Search Tag Analyze Resource for Gene Expression Omnibus (STARGEO) platform to identify 39 TOF and 19 non-TOF right ventricle tissue samples from microarray data and identified upregulated and downregulated genes. Associated gene expression data were analyzed using ingenuity pathway analysis and restricted to genes with a statistically significant (p < .05) difference and an absolute experimental log ratio >0.1 between disease and control samples. RESULTS: Our analysis identified 220 genes whose expression profiles were significantly altered in TOF vs. non-TOF samples. The most striking differences identified in gene expression included genes FBXO32, PTGES, MYL12a, and NR2F2. Some top associated canonical pathways included adrenergic signaling, estrogen receptor signaling, and the role of NFAT in cardiac hypertrophy. In general, genes involved in adaptive, defensive, and reparative cardiovascular responses showed altered expression in TOF vs. non-TOF samples. CONCLUSIONS: We introduced the interpretation of open "big data" using the STARGEO platform to define robust genomic signatures of congenital heart disease pathology of TOF. Overall, our meta-analysis results indicated increased metabolism, inflammation, and altered gene expression in TOF patients. Estrogen receptor signaling and the role of NFAT in cardiac hypertrophy represent unique pathways upregulated in TOF patients and are potential targets for future pharmacologic treatments.

Baseline-to-loaded changes in regional tibial cartilage thickness, T1ρ and T2: Utilization of an MRI compatible loading device.

The objective of the study was to evaluate tibial cartilage thickness (TCT), T1ρ and T2 values within both loaded and baseline configurations in a cadaveric knee model using a 3D bone based tibial coordinate system. Ten intact cadaveric knees were mounted into an magnetic resonance imaging (MRI) compatible loading device. Morphologic and quantitative MRI (qMRI) images were acquired with the knee in a baseline configuration and after application of 50% body weight. The morphologic images were evaluated for cartilage degeneration using a modified Noyes scoring system. A 3D bone-based tibial coordinate system was utilized to evaluate regional changes of tibial T1ρ, T2, and cartilage thickness values among regions covered and uncovered by the meniscus. Inter-regional differences in medial and lateral MRI outcomes were found between loaded and baseline configurations. Cartilage regions covered by the meniscus demonstrated disparate qMRI and TCT results as compared to cartilage regions not covered by the meniscus. The regions covered by meniscus experienced a ~3.5%, ~0.5%, and ~5.5% reduction of T1ρ (p < 0.05, medial and lateral compartments), T2 and TCT, respectively, in both compartments while regions not covered by the meniscus experienced larger reductions of ~10%, ~2%, and ~10.5% reduction of T1ρ (p < 0.05, medial and lateral compartments), T2 and TCT (p < 0.05, lateral compartment only), respectively, in both compartments. T1ρ and T2 decreases following application of 50% body weight load were substantially larger in the tibial regions with modified Noyes grade 3 (n = 2) compared to either healthy regions (n = 85, p < 0.0.003) or regions with modified Noyes grade 2 (n = 13, p < 0.004). Interregional differences in MRI outcomes reflect variations in structure and function, and largely followed a pattern in cartilage regions that were covered or not covered by the meniscus. Results of the current study suggest that ΔT1ρ and ΔT2 values may be sensitive to superficial fissuring, more than baseline or loaded T1ρ or T2 values, or TCT alone, however future studies with additional specimens, with greater variability in OA grade distribution, may further emphasize the current findings.

Tekscan analysis programs (TAP) for quantifying dynamic contact mechanics.

This short communication provides details on customized Tekscan Analysis Programs (TAP) which extract comprehensive contact mechanics metrics from piezoelectric sensors in articulating joints across repeated loading cycles. The code provides functionality to identify regions of interest (ROI), compute contact mechanic metrics, and compare contact mechanics across multiple test conditions or knees. Further, the variability of identifying ROIs was quantified between seven different users and compared to an expert. Overall, the contribution of four variables were studied: two knee specimens; two points in the gait cycle; two averaging methods; and seven observers, to determine if variations in these values played a role in accurately quantifying the ROI. The relative error between the force ratio from each observer's ROI and the expert ROI was calculated as the output of interest. A multivariate linear mixed effects model was fit to the four variables for the relative error with an observer- and knee-specific random intercept. Results from the fitted model showed a statistically significant difference at the 0.05 level in the mean relative errors at the two gait points. Additionally, variability in the relative errors attributed to the observer, knee, and random errors was quantified. To reduce variability amongst users, by ensuring low inter-observer variability and increasing segmentation accuracy of knee contact mechanics, a training module and manual have been included as supplemental material. By sharing this code and training manual, we envisage that it can be used and modified to analyze outputs from a range of sensors, joints, and test conditions.

ACL transection results in a posterior shift and increased velocity of contact on the medial tibial plateau.

Our objective was to quantify the effect of ACL transection on dynamic knee joint contact force distributions during simulated gait. Given the prevalence of medial compartment osteoarthritis in un-reconstructed ACL ruptured knees, we hypothesized that changes in contact mechanics after ACL transection would be most prevalent in the medial compartment. Twelve human cadaveric knees were tested using a dynamic knee gait simulator which was programmed to mimic a clinical Lachman exam and gait. An electronic pressure sensor was placed on the medial and lateral tibial plateaus under the menisci to quantify dynamic contact forces before and after ACL transection. Tibial translations and rotations, medial and lateral plateau peak contact stress, and position and velocity of the Weighted Center of Contact (WCoC) were computed. After ACL transection, the tibia translated more anteriorly in the Lachman examination and at heel strike during gait. Changes in contact mechanics across the medial tibial plateau during simulated gait were: an increase in the velocity of WCoC and a posterior shift in the WCoC, both of which occurred at heel strike; increased peak contact forces in the posterior-peripheral quadrant of the tibial plateau at 45% of the gait cycle; and an additional posterior shift in WCoC from 25 to 55% of the gait cycle. The only change in contact mechanics in the lateral plateau was a decrease in WCoC velocity in late stance. This data is suggested to further the study of biomechanical pathways (biomechanical biomarkers) in the relationship between altered knee contact mechanics and chondrocyte metabolic responses after ACL transection.

MRL/MpJ tendon matrix-derived therapeutic promotes improved healing outcomes in scar-mediated canonical tendon healing.

Tendons are commonly injured connective soft tissues characterized by an ineffective healing response that results in scar formation and loss of functional and structural properties. Naturally occurring extracellular matrix (ECM) constructs have become a promising therapeutic for tendon injuries due to their capacity to harness a complex biological environment. However, in tendon, the ECM properties needed for improved healing remain unknown. Interestingly, we have determined that the improved tendon healing response of the scarless-healing MRL/MpJ is driven by intrinsic properties with therapeutic potential to modulate the proliferative and morphological behavior of cells derived from a canonically healing model in vitro. We hypothesize that a distinct composition of ECM deposited during the early healing response of the MRL/MpJ will harnesses the biological cues to stimulate improved structure and function in vivo of canonically healing B6 mice. Accordingly, MRL/MpJ and B6 patellar tendons were injured via midsubstance punch defects. Healing tendons were isolated after 3 or 7 days and encapsulated in PEG-4MAL hydrogels to develop ECM-derived therapeutic constructs. Constructs were then introduced into B6 mice as a treatment following full thickness midsubstance-punch injuries. Treatment with ECM-derived constructs from MRL/MpJ tendons after 7-days post-injury (M7) resulted in improved matrix alignment, tissue stiffness, decreased collagen III content and improved cell morphology in B6 tendons after 6 weeks post-injury. Furthermore, proteomic analysis showed that M7 contained a unique compositional profile rich in glycoproteins, thereby elucidating a valuable naturally-derived platform for the treatment of tendon injuries. Overall this work highlights promising targets for future therapeutic development and tissue engineering applications.