Protein-metal interactions due to fretting corrosion at the taper junction of hip implants: An in vitro investigation using Raman spectroscopy.

Modular hip implants are a clinically successful and widely used treatment for patients with arthritis. Despite ongoing retrieval studies the understanding of the fundamental physico-chemical mechanisms of friction and wear within the head-taper interface is still limited. Here, we Raman-spectroscopically analyze structural features of the biotribological material which is formed within the taper joint between Ti6Al4V and low-carbon cobalt alloy or high-nitrogen steel surfaces in in vitro gross-slip fretting corrosion tests with bovine calf serum. As a function of the fretting duration, we investigate short and long aliphatic chains and their adsorption behavior on the cobalt- and steel-type surfaces. Using the intensity and frequency shifts of the amide I and III Raman bands, we furthermore identify progressive protein folding and unfolding including the secondary structures of α-helix, ß-sheet, and random-coil configuration as well as the formation of proteinaceous clusters depending on the hydrophilicity of the metallic surfaces. We additionally find a mixture of chromates and iron oxides with tryptophan and tyrosine at the worn cobalt alloy and high-nitrogen steel surfaces, respectively. Also, for long fretting duration, sp2 hybridized amorphous carbon is formed due to fretting-induced cleavage of proteins. STATEMENT OF SIGNIFICANCE: Despite efforts enhancing the biomedical tribology of hip implants, the impact of the organic environment on friction and wear at the femoral head-stem taper interface is limitedly understood. Using Raman spectroscopy we resolve structural changes within the biotribological material agglomerated at biomedical-grade metal alloys due to metal-organic interactions during in vitro fretting corrosion tests. Adsorption of short and long aliphatic chains, progressive protein (un)folding and proteinaceous cluster formation depend to a distinguishable extent on the fretting duration and type of alloy. Chromates and iron oxides are mixed with tryptophan and tyrosine, and amorphous carbon is formed resulting from a fretting-induced cleavage of serum proteins. Such information spectroscopically gleaned from biotribological material are vital to improve the design and performance of taper junctions.

Association between Dexmedetomidine Use and Mortality in Patients with COVID-19 Receiving Invasive Mechanical Ventilation: A U.S. National COVID Cohort Collaborative (N3C) Study.

(1) Background/Objectives: Dexmedetomidine is a sedative for patients receiving invasive mechanical ventilation (IMV) that previous single-site studies have found to be associated with improved survival in patients with COVID-19. The reported clinical benefits include dampened inflammatory response, reduced respiratory depression, reduced agitation and delirium, improved preservation of responsiveness and arousability, and improved hypoxic pulmonary vasoconstriction and ventilation-perfusion ratio. Whether improved mortality is evident in large, multi-site COVID-19 data is understudied. (2) Methods: The association between dexmedetomidine use and mortality in patients with COVID-19 receiving IMV was assessed. This retrospective multi-center cohort study utilized patient data in the United States from health systems participating in the National COVID Cohort Collaborative (N3C) from 1 January 2020 to 3 November 2022. The primary outcome was 28-day mortality rate from the initiation of IMV. Propensity score matching adjusted for differences between the group with and without dexmedetomidine use. Adjusted hazard ratios (aHRs) for 28-day mortality were calculated using multivariable Cox proportional hazards models with dexmedetomidine use as a time-varying covariate. (3) Results: Among the 16,357,749 patients screened, 3806 patients across 17 health systems met the study criteria. Mortality was lower with dexmedetomidine use (aHR, 0.81; 95% CI, 0.73-0.90; p < 0.001). On subgroup analysis, mortality was lower with earlier dexmedetomidine use-initiated within the median of 3.5 days from the start of IMV-(aHR, 0.67; 95% CI, 0.60-0.76; p < 0.001) as well as use prior to standard, widespread use of dexamethasone for patients on respiratory support (prior to 30 July 2020) (aHR, 0.54; 95% CI, 0.42-0.69; p < 0.001). In a secondary model that was restricted to 576 patients across six health system sites with available PaO2/FiO2 data, mortality was not lower with dexmedetomidine use (aHR 0.95, 95% CI, 0.72-1.25; p = 0.73); however, on subgroup analysis, mortality was lower with dexmedetomidine use initiated earlier than the median dexmedetomidine start time after IMV (aHR, 0.72; 95% CI, 0.53-0.98; p = 0.04) and use prior to 30 July 2020 (aHR, 0.22; 95% CI, 0.06-0.78; p = 0.02). (4) Conclusions: Dexmedetomidine use was associated with reduced mortality in patients with COVID-19 receiving IMV, particularly when initiated earlier, rather than later, during the course of IMV as well as use prior to the standard, widespread usage of dexamethasone during respiratory support. These particular findings might suggest that the associated mortality benefit with dexmedetomidine use is tied to immunomodulation. However, further research including a large randomized controlled trial is warranted to evaluate the potential mortality benefit of DEX use in COVID-19 and evaluate the physiologic changes influenced by DEX that may enhance survival.

Performance of Austenitic High-Nitrogen Steels under Gross Slip Fretting Corrosion in Bovine Serum.

Modular artificial hip joints are a clinical standard today. However, the release of wear products from the head-taper interface, which includes wear particles in the nm size range, as well as metal ions, have raised concerns. Depending on the loading of such taper joints, a wide variety of different mechanisms have been found by retrieval analyses. From these, this paper concentrates on analyzing the contribution of gross slip fretting corrosion at ultra-mild wear rates using a bovine calf serum solution (BCS) as the lubricant. The parameters were chosen based on biomechanical considerations, producing wear rates of some ng/m wear path. In parallel, the evolution of tribomaterial (third bodies) was analyzed as to its constituents and generation rates. It has already been shown earlier that, by an advantageous combination of wear mechanisms and submechanisms, certain constituents of the tribomaterial remain inside the contact area and act like extreme-pressure lubricant additives. For the known wear and corrosion resistance of austenitic high-nitrogen steels (AHNSs), which outperform CoCrMo alloys even under inflammatory conditions, we hypothesized that such steels will generate ultra-mild wear rates under gross slip fretting. While testing AHNSs against commercially available biomedical-grade materials of CoCrMo and TiAlV alloys, as well as zirconia-toughened alumina (ZTA) and against itself, it was found that AHNSs in combination with a Ti6Al4V alloy generated the smallest wear rate under gross slip fretting corrosion. This paper then discusses the wear behavior on the basis of ex situ analyses of the worn surfaces as to the acting wear mechanisms and submechanisms, as well as to the tribological reaction products.

Hip joint contact forces are lower in people with femoroacetabular impingement syndrome during squat tasks.

It remains unknown if hip joint forces during squat tasks are altered in people with femoroacetabular impingement syndrome (FAIS). The aim of this study is to compare hip joint forces between people with FAIS and healthy controls during double leg squat and single leg squat tasks and within limbs during a single leg squat task in people with FAIS. Kinematic and kinetic data were collected in eight people with FAIS and eight healthy matched controls using 3D motion capture and force plates. AnyBody Modeling System was used to perform musculoskeletal simulations to estimate hip joint angles, forces, and moments for all participants. Estimates were postprocessed with AnyPyTools and converted into normalized time series to be compared using a 1D statistical nonparametric mapping (SnPM) approach. SnPM with an independent samples t-test model was used to compare people with FAIS to controls, while a paired samples model was used to compare involved to uninvolved limb in people with FAIS. Patients demonstrated lower proximodistal force compared to controls (p < 0.01) and compared to the uninvolved side (p = 0.01) for single leg squat. The smaller joint contact forces in people with FAIS compared to controls could represent a strategy of reduced muscle forces to avoid pain and symptoms during this high demand task. These findings when combined with imaging data could help assess the severity of FAIS on hip related function during higher demand tasks.

Striated Pattern on Worn Surface of a Retrieved TKR Tibial Insert Stems from Microstructural Changes in the UHMWPE.

Polyethylene wear has been a concern for the longevity of total knee replacements (TKR). A characteristic wear feature often observed on the articular surfaces of retrieved polyethylene tibial inserts is a striated pattern of hills and troughs. This pattern is of interest because its surface area has been found to correlate with increased tibial insert wear. We therefore addressed the following two research questions: (1) What is the prevalence of the striated pattern on a contemporary tibial insert design made from conventional ultra-high-molecular-weight polyethylene (UHMWPE)? (2) Are the peaks and troughs of the striated pattern connected with differences in crystallinity developed during the wear process? The prevalence and area coverage of the striated patterns were determined on a set of 81 retrieved tibial inserts of a cruciate-retaining TKR design. The striated areas were mapped using an optical coordinate measuring machine. Differences in crystallinity between troughs and hills were determined on a representative tibial insert using Raman spectroscopy. The striated pattern was observed on 61 out of 81 (75%) of the retrieved tibial inserts, covering an average of 32% of the total articular area. In the representative insert that was evaluated, the hills exhibited higher crystallinity (68%) than the troughs (54%) (p = 0.001). Conversely, the troughs exhibited higher amorphous phase content (22%) than the hills (19%) (p = 0.04). In conclusion, this pattern of hills and troughs is another example of microstructural changes in UHMWPE stemming from tribological stresses.

Zucker Diabetic-Sprague Dawley Rats Have Impaired Peri-Implant Bone Formation, Matrix Composition, and Implant Fixation Strength.

An increasing number of patients with type 2 diabetes (T2DM) will require total joint replacement (TJR) in the next decade. T2DM patients are at increased risk for TJR failure, but the mechanisms are not well understood. The current study used the Zucker Diabetic-Sprague Dawley (ZDSD) rat model of T2DM with Sprague Dawley (SPD) controls to investigate the effects of intramedullary implant placement on osseointegration, peri-implant bone structure and matrix composition, and fixation strength at 2 and 10 weeks post-implant placement. Postoperative inflammation was assessed with circulating MCP-1 and IL-10 2 days post-implant placement. In addition to comparing the two groups, stepwise linear regression modeling was performed to determine the relative contribution of glucose, cytokines, bone formation, bone structure, and bone matrix composition on osseointegration and implant fixation strength. ZDSD rats had decreased peri-implant bone formation and reduced trabecular bone volume per total volume compared with SPD controls. The osseointegrated bone matrix of ZDSD rats had decreased mineral-to-matrix and increased crystallinity compared with SPD controls. Osseointegrated bone volume per total volume was not different between the groups, whereas implant fixation was significantly decreased in ZDSD at 2 weeks but not at 10 weeks. A combination of trabecular mineral apposition rate and postoperative MCP-1 levels explained 55.6% of the variance in osseointegration, whereas cortical thickness, osseointegration mineral apposition rate, and matrix compositional parameters explained 69.2% of the variance in implant fixation strength. The results support the growing recognition that both peri-implant structure and matrix composition affect implant fixation and suggest that postoperative inflammation may contribute to poor outcomes after TJR surgeries in T2DM patients. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Translational Characterization of Macrophage Responses to Stable and Non-Stable CoCrMo Wear and Corrosion Debris Generated In-Situ for Total Hip Replacement.

Metal wear and corrosion debris remain a limiting factor for long-term durability of total hip replacement (THR). Common wear particle production techniques for research differ from the actual tribocorrosion processes at the implant site, potentially causing loss of valuable information. The aim of this study was to investigate reactions to freshly generated and time-stabilized particles and ions released from CoCrMo-alloy using a bio-tribometer, which mimics conditions of the periprosthetic environment. THP-1 macrophages were challenged with freshly produced or time-stabilized wear debris. Wear generation took place in a custom-built bio-tribometer inside a CO2 incubator operating with a reciprocating rotation of an Al2O3 ball against a CoCrMo disc. Two different electrochemical conditions with increasingly forced corrosion rates were tested: +0.45 V (passive domain) and +0.67 V (transition to transpassive domain). Cell viability, proinflammatory cytokines, electrochemical measurements and ICP-MS metal ion content analyses were performed. Cobalt/ chromium concentrations were 6.6/ 1.6 ppm in the passive domain and almost doubled to 11.4/ 3.0 ppm in the passive-transpassive domain. Under those electrochemical conditions, freshly produced and time-stabilized CoCrMo wear decreased cell viability to the same extent. Secretion of proinflammatory cytokines were not significantly different for freshly produced and time-stabilized debris. This study suggests that freshly generated and time-stabilized metal particles/ions cause similar toxicity and inflammatory reactions in macrophages, indicating that standard practices for generating wear debris are valid methods to evaluate wear particle disease. Other cell types, materials, and corrosion potentials need to be studied in the future to solidify the conclusion.

Development of a computational-experimental framework for enhanced mechanical characterization and cross-species comparison of the articular cartilage superficial zone.

To provide a better understanding of the contribution of specific constituents (i.e. proteoglycan, collagen, fluid) to the mechanical behavior of the superficial zone of articular cartilage, a complex biological tissue with several time-dependent properties, a finite element model was developed. Optimization was then used to fit the model to microindentation experiments. We used this model to compare superficial zone material properties of mature human vs. immature bovine articular cartilage. Non-linearity and stiffness of the fiber-reinforced component of the model differed between human and bovine tissue. This may be due to the more complex collagen architecture in mature tissue and is of interest to investigate in future work.

Electrophoretic deposition of gentamicin and chitosan into titanium nanotubes to target periprosthetic joint infection.

Periprosthetic joint infection (PJI) occurs in 1%-2% of primary total hip and knee arthroplasties; the rate can reach 20% in individuals at risk. Due to the low local bioavailability of systemic antibiotics and possible off-target effects, localized drug delivery systems are of great importance. Our aim was the electrophoretic deposition (EPD) of gentamicin and chitosan in Titanium (Ti) nanotubes to establish a local, prolonged antibiotic delivery. Nanotubes were created on Ti wire with a two-step anodization process. For drug deposition, EPD and the air-dry methods were compared. For a prolonged drug release, gentamicin and crosslinked chitosan were deposited in a two-step EPD process. Drug release was quantified by fractional volume sampling. The Ti wires were tested against Staphylococcus aureus by agar dilution and liquid culture methods. MC3T3-E1 osteoblastic cell viability was determined with trypan blue. Nanotubes were characterized by a 100 nm diameter and 7 µm length. EPD allowed a higher amount of gentamicin deposited than the air-dry method. Drug deposition was controllable by adjusting the voltage and duration of the EPD process. The crosslinked chitosan layer allowed diffusion-driven release kinetics for up to 3 days. Gentamicin-loaded Ti wires significantly inhibited bacterial growth and resulted in a larger inhibition zone compared to unloaded wires. Twenty-four hours of incubation with loaded wires did not have a significant effect on osteoblast viability. Gentamicin-loaded Ti nanotubes represent a promising approach for PJI prevention, as well as a valuable preclinical tool for the investigation of localized drug delivery systems created on Ti surface.

Accuracy of the fully integrated Insole3's estimates of spatiotemporal parameters during walking.

This study investigated the accuracy of the Insole3 wireless shoe device in estimating several clinically useful spatiotemporal parameters (STPs). Eleven subjects walked at slow (0.8-1.0 m/s) and moderate-paced (1.2-1.4 m/s) speeds. Data were simultaneously recorded using the Insole3 and an industry-standard, three-dimensional motion capture (MOCAP) system. An error analysis compared the resulting STP data from the two systems. The mean bias error (MBE) was generally lower for temporal variables, and somewhat higher, but acceptable, for spatial variables. The MBE for temporally-related cadence and cycle time were the lowest (less than ±0.45%), with 100% (110/110) of slow-paced walking trial values and 99.1% (109/110) of moderate-paced walking trial values within 5% of the MOCAP estimates. The MBE was highest for speed (3.23-4.91%) and stride length (3.68-4.63%), with between 52.7 and 69.1% of trial values falling within the 5% error range. Stance time and swing time ranged between -0.98 and 4.38% error for both walking conditions. The results of this study suggest that the Insole3 is a potential alternative to MOCAP for estimating several STPs, namely cadence, stance time, and cycle time, particularly for use outside of the laboratory setting.

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.

Validity and Reliability of the Insole3 Instrumented Shoe Insole for Ground Reaction Force Measurement during Walking and Running.

Pressure-detecting insoles such as the Insole3 have potential as a portable alternative for assessing vertical ground reaction force (vGRF) outside of specialized laboratories. This study evaluated whether the Insole3 is a valid and reliable alternative to force plates for measuring vGRF. Eleven healthy participants walked overground at slow and moderately paced speeds and ran at a moderate pace while collecting vGRF simultaneously from a force plate (3000 Hz) and Insole3 (100 Hz). Intraclass correlation coefficients (ICC) demonstrated excellent vGRF agreement between systems during both walking speeds for Peak 1, Peak 2, the valley between peaks, and the vGRF impulse (ICC > 0.941). There was excellent agreement during running for the single vGRF peak (ICC = 0.942) and impulse (ICC = 0.940). The insoles slightly underestimated vGRF peaks (−3.7% to 0.9% bias) and valleys (−2.2% to −1.8% bias), and slightly overestimated impulses (4.2% to 5.6% bias). Reliability between visits for all three activities was excellent (ICC > 0.970). The Insole3 is a valid and reliable alternative to traditional force plates for assessing vGRF during walking and running in healthy adults. The excellent ICC values during slow walking suggests that the Insole3 may be particularly suitable for older adults in clinical and home settings.

Biotribometer for Assessment of Cell and Tissue Toxicity of Orthopedic Metal Implant Debris.

A novel approach to address the clinical issue of cell response to wear and corrosion debris from metal orthopedic implants consists of combining cell culturing with wear and corrosion debris generation. A biotribometer equipped with a three-electrode electrochemical chamber operates inside a CO2 incubator. Cells are cultured at the bottom of the chamber. A ceramic ball (hip implant head) is pressed against a metal disc under a constant load, and set in reciprocating rotation. An anodic electrochemical potential can be applied to a metal disc for accelerated corrosion conditions, or the free potential may be monitored.Measurements of gravimetric and volumetric material loss of the metal disc postwear provide quantitative information that can be put in relation to biological assays (e.g., cell viability and secretion of proinflammatory cytokines). This approach allows for the comparison of candidate metals potentially undergoing tribocorrosion in clinical use. The approach allows to identify the effect of any metastable debris, likely active in vivo.

The relative contribution of bone microarchitecture and matrix composition to implant fixation strength in rats.

Bone microarchitectural parameters significantly contribute to implant fixation strength but the role of bone matrix composition is not well understood. To determine the relative contribution of microarchitecture and bone matrix composition to implant fixation strength, we placed titanium implants in 12-week-old intact Sprague-Dawley rats, ovariectomized-Sprague-Dawley rats, and Zucker diabetic fatty rats. We assessed bone microarchitecture by microcomputed tomography, bone matrix composition by Raman spectroscopy, and implant fixation strength at 2, 6, and 10 weeks postimplantation. A stepwise linear regression model accounted for 83.3% of the variance in implant fixation strength with osteointegration volume/total volume (50.4%), peri-implant trabecular bone volume fraction (14.2%), cortical thickness (9.3%), peri-implant trabecular crystallinity (6.7%), and cortical area (2.8%) as the independent variables. Group comparisons indicated that osseointegration volume/total volume was significantly reduced in the ovariectomy group at Week 2 (~28%) and Week 10 (~21%) as well as in the diabetic group at Week 10 (~34%) as compared with the age matched Sprague-Dawley group. The crystallinity of the trabecular bone was significantly elevated in the ovariectomy group at Week 2 (~4%) but decreased in the diabetic group at Week 10 (~3%) with respect to the Sprague-Dawley group. Our study is the first to show that bone microarchitecture explains most of the variance in implant fixation strength, but that matrix composition is also a contributing factor. Therefore, treatment strategies aimed at improving bone-implant contact and peri-implant bone volume without compromising matrix quality should be prioritized.

Nickel-free high-nitrogen austenitic steel outperforms CoCrMo alloy regarding tribocorrosion in simulated inflammatory synovial fluids.

CoCrMo alloys are well-established biomaterials used for orthopedic joint replacement implants. However, such alloys have been associated with clinical problems related to wear and corrosion. A new generation of austenitic high-nitrogen steels (AHNSs) has been developed for biomedical applications. Here, we have addressed influences of hyaluronic acid, combined with inflammatory (oxidizing) conditions, on tribocorrosion of the high-nitrogen FeCrMnMoN0.9 steel (DIN/EN X13CrMnMoN18-14-3, 1.4452), and of the low carbon CoCrMo0.03 alloy (ISO 5832-12). We aimed to elucidate critical and clinically relevant conditions affecting the implant's performance in certain orthopedic applications. Tribocorrosion tests were conducted in triplicate, with discs under reciprocating sliding wear against a ceramic ball. Different lubricants were prepared from standardized bovine serum solution (ISO 14242-1), with variable additions of hyaluronic acid (HA) and hydrogen peroxide (H2 O2 ). Test conditions were: 37°C, 86,400 cycles, 37 N load (20-40 MPa after run-in phase). Volumetric wear was quantified; surfaces were evaluated by electrochemical parameters and microscopy/spectroscopy analyses (SEM/EDS). Factorial analysis of variance tests was conducted to examine the effects of HA, H2 O2 , and test material on wear- and corrosion-related dependent variables. Tribocorrosion performances of CoCrMo0.03 and FeCrMnMoN0.9 were comparable in fluids without H2 O2 . With higher H2 O2 concentrations, tribocorrosion increased for CoCrMo0.03 , while this was not the case for FeCrMnMoN0.9 . HA significantly enhanced wear of CoCrMo0.03 in the absence of H2 O2 , while it mitigated the tribocorrosive action of 3 mM H2 O2 ; HA had no impact on FeCrMnMoN0.9 . These results indicate a favorable performance of FeCrMnMoN0.9 compared to CoCrMo0.03 , and encourage further research on AHNS for certain orthopedic applications.

Optimal surgical component alignment minimizes TKR wear - An in silico study with nine alignment parameters.

Currently, preclinical mechanical wear testing of total knee replacements (TKRs) is done using ideally aligned components using standardized TKR level walking under either force or displacement-control regimes. To understand the influence of implant alignment and testing control regime, we studied the effect of nine component alignment parameters on TKR volumetric wear in silico. We used a computational framework combining Latin Hypercube sampling design of experiments, finite element analysis, and a numerical model of polyethylene wear, to create a predictive model of how component alignment affects wear rate for each control regime. Nine component alignment parameters were investigated, five femoral variables and four tibial variables. To investigate perturbations of the nine implant alignment variables, two separate 300-point designs were executed, one for each control regime. The results were then used to generate surrogate statistical models using stepwise multiple linear regression. Wear at the neutral position was 4.5mm3/million cycle and 8.6mm3/million cycle for displacement and force-control, respectively. Stepwise multiple linear regression surrogate models were highly significant for each control regime, but force-control generated a stronger predictive model, with a higher R2, more included terms, and a lower RMSE. Both models predicted transverse plane rotational mismatch can lead to large changes in predicted wear; a transverse plane alignment mismatch of 15° can elicit a change in wear of up to 5mm3/million cycle, almost double that of neutral alignment. Therefore, transverse plane alignment is particularly important when considering failure of the implant due to wear.

A MOVING CONTACT OF ARTICULATION ENHANCES THE BIOSYNTHETIC AND FUNCTIONAL RESPONSES OF ARTICULAR CARTILAGE.

Biomechanical influences play a fundamental role in the structural, functional, and biosynthetic properties of articular cartilage. During physiologic joint loading, the contact area between two surfaces migrates due to the primary and secondary motions of the joint. It has been demonstrated that a migratory contact area plays a critical role in reducing the coefficient of friction at the cartilage surface. However, a detailed analysis of the influences that a migratory contact area plays on the structural, functional, and biosynthetic properties remain to be explored. In this study, bovine cartilage explants were placed in a biotribometer. Explants were subjected to compression and shear forces of migratory contact area, namely moving contact (MC) articulation, or stationary contact area, namely stationary contact (SC) articulation. Free swelling explants were used as control. In a separate study, bovine cartilage-bone grafts were used for frictional testing. On histologic analysis, the SC group had evidence of surface fibrillations, which was not evident in the MC group. Compared to the SC group, the MC group cartilage explants had increased chondrocyte viability, increased lubricin synthesis, and comparable proteoglycan synthesis and release. MC articulation had reduced coefficient of friction as compared to SC articulation. MC articulation led to reduced surface roughness as compared to SC articulation. In conclusion, a migratory contact area can play an important role in maintaining the structural, function, and biosynthetic properties of articular cartilage. This study provides further evidence of the importance of migratory contact area and in vitro assessment of natural joint movement, which can be further evaluated in the context of cartilage homeostasis and disease.

Fretting-corrosion in hip taper modular junctions: The influence of topography and pH levels - An in-vitro study.

Contemporary hip implants feature a modular design. Increased reported failure rates associated with the utilization of modular junctions have raised many clinical concerns. Typically, these modular interfaces contain circumferential machining marks (threads or microgrooves), but the effect of the machining marks on the fretting-corrosion behavior of total hip implant materials is unknown. This study reports the effects of microgrooves on the fretting-corrosion behavior of hip implant materials. The flat portions of two cylindrical, polished, CrCrMo alloy pins were loaded horizontally against one rectangular Ti alloy rod. Two surface preparation groups were used for the Ti6Al4V rod (polished and machined). The polished group was prepared using the same methods as the CoCrMo pins. The machined samples were prepared by creating parallel lines on the rod surfaces to represent microgrooves present on the stem tapers of head-neck modular junctions. Newborn calf serum (30 g/L protein content; 37 °C) at pH of levels of 7.6 and 3.0 were used to simulate the normal joint fluid and a lowered pH within a crevice, respectively. The samples were tested in a fretting corrosion apparatus under a 200N normal force and a 1Hz sinusoidal fretting motion with a displacement amplitude of 25 µm. All electrochemical measurements were performed with a potentiostat in a three-electrode configuration. The results show significant differences between machined samples and polished samples in both electrochemical and mechanical responses. In all cases, the magnitude of the drop in potential was greater in the machined group compared to the polished group. The machined group showed a lower total dissipated friction energy for the entire test compared to the polished group. Additionally, the potentiostatic test measurements revealed a higher evolved charge in the machined group compared to the polished group at both pH conditions (pH 7.6 and 3.0). The machined surfaces lowered the overall dissipated friction energy at pH 7.6 compared to pH 3.0, but also compromised electrochemical performance in the tested conditions. Therefore, the role of synergistic interaction of wear and corrosion with surface topographical changes is evident from the outcome of the study. Despite the shift towards higher electrochemical destabilization in the machined group, both polished and machined groups still exhibited a mechanically dominated degradation.

The Association of an Alpha-2 Adrenergic Receptor Agonist and Mortality in Patients With COVID-19.

There is a need for treatments to reduce coronavirus disease 2019 (COVID-19) mortality. Alpha-2 adrenergic receptor (α2 AR) agonists can dampen immune cell and inflammatory responses as well as improve oxygenation through physiologic respiratory parameters. Therefore, α2 AR agonists may be effective in reducing mortality related to hyperinflammation and acute respiratory failure in COVID-19. Dexmedetomidine (DEX) is an α2 AR agonist used for sedation. We performed a retrospective analysis of adults at Rush University System for Health hospitals between March 1, 2020 and July 30, 2020 with COVID-19 requiring invasive mechanical ventilation and sedation (n = 214). We evaluated the association of DEX use and 28-day mortality from time of intubation. Overall, 28-day mortality in the cohort receiving DEX was 27.0% as compared to 64.5% in the cohort that did not receive DEX (relative risk reduction 58.2%; 95% CI 42.4-69.6). Use of DEX was associated with reduced 28-day mortality on multivariable Cox regression analysis (aHR 0.19; 95% CI 0.10-0.33; p < 0.001). Adjusting for time-varying exposure to DEX also demonstrated that DEX was associated with reduced 28-day mortality (aHR 0.51; 95% CI 0.28-0.95; p = 0.03). Earlier DEX use, initiated <3.4 days from intubation, was associated with reduced 28-day mortality (aHR 0.25; 95% CI 0.13-0.50; p < 0.001) while later DEX use was not (aHR 0.64; 95% CI 0.27-1.50; p = 0.30). These results suggest an α2 AR agonist might reduce mortality in patients with COVID-19. Randomized controlled trials are needed to confirm this observation.