High-Speed Strain Mapping of Human Meniscus During Tensile Loading

The knee meniscus is a fibrous soft tissue that is frequently torn. Prevention and treatment requires an understanding of failure mechanisms. Important failure properties are currently unknown, including the magnitude and orientation of principal strains at failure. This information is needed to inform predictive failure theories. 8 human meniscal samples were failed in tension, and surface strains were tracked using a previously validated high-speed digital image correlation system. Results suggest that failures occur at 44°, along the maximum shearing plane when testing along the reinforcing fibers, and at 6° along the maximum tensile plane when testing normal to reinforcing fibers

Finite Element Modeling of Meniscal Tears Using Continuum Damage Mechanics and Digital Image Correlation

Meniscal tears are a common, painful, and debilitating knee injury with limited treatment options. Computational models that predict meniscal tears may help advance injury prevention and repair, but first these models must be validated using experimental data. Here we simulated meniscal tears with finite element analysis using continuum damage mechanics (CDM) in a transversely isotropic hyperelastic material. Finite element models were built to recreate the coupon geometry and loading conditions of forty uniaxial tensile experiments of human meniscus that were pulled to failure either parallel or perpendicular to the preferred fiber orientation. Two damage criteria were evaluated for all experiments: von Mises stress and maximum normal Lagrange strain. After we successfully fit all models to experimental force–displacement curves (grip-to-grip), we compared model predicted strains in the tear region at ultimate tensile strength to the strains measured experimentally with digital image correlation (DIC). In general, the damage models underpredicted the strains measured in the tear region, but models using von Mises stress damage criterion had better overall predictions and more accurately simulated experimental tear patterns. For the first time, this study has used DIC to expose strengths and weaknesses of using CDM to model failure behavior in soft fibrous tissue

A Computational Tool to Automate the Analysis of Stress-Strain Data from Tensile Tests of Soft Tissue

Stress-strain curves are commonly generated to analyze the mechanical tensile behavior of biological materials and evaluate several key points. There is no standard method to find the transition point. Additionally, there is a need for a user-friendly program that automates the calculation of mechanical properties from stress-strain curves. A custom graphical user interface (GUI) was created using Python, allowing users to upload stress-strain data where it automatically generates a stress-strain curve with marked points of interest, as well as a .csv file that appends those points. The software\u27s accuracy was evaluated using tensile test data from our previous study on human meniscus and synthetic stress-strain curves with known transition points generated using FEBio studio. The GUI closely predicted the same transition point calculated using a more complex FE optimization routine. We found that a 3% slope deviation returned the lowest error for transition stress in this study. The error in calculating the transition point was insensitive to changes in the modulus and damage rate of the stress-strain curve. In conclusion, by creating an accurate computational tool to automate the analysis of stress-strain curves, this study can advance the standardization of biomechanical testing in soft fibrous tissue

Dots-on-Plots: A Web Application to Analyze Stress–Strain Curves From Tensile Tests of Soft Tissue

The calculation of tensile mechanical properties from stress–strain curves is a fundamental step in characterizing material behavior, yet no standardized method exists to perform these calculations for soft tissue. To address this deficiency, we developed a free web application called Dots-on-Plots that fully automates the calculation of tensile mechanical properties from stress–strain curves. The analyzed mechanical properties include the strength, strain, and energy at four points of interest (transition, yield, ultimate, and rupture), and the linear modulus. Users of Dots-on-Plots can upload multiple files, view and download results, and adjust threshold settings. This study determined a threshold setting that minimized error when calculating the transition point, where the stress–strain curve “transitions” from a nonlinear “toe” region to a linear region. Using the optimal threshold (2% stress deviation from a linear region fit), Dots-on-Plots calculated the transition strains from twenty tensile experiments of human meniscus to be 0.049 ± 0.007, which nearly matched the known transition strain values of 0.050 ± 0.006 (determined using finite element parameter optimization). The sensitivity of the calculated transition strain to the shape of various stress–strain curves was analyzed using sets of model-generated synthetic data. This free web application offers a convenient and reliable tool to systematically enhance the speed, transparency, and consistency of mechanical analysis across biomedical research groups

Effect of Age on the Failure Properties of Human Meniscus: High-Speed Strain Mapping of Tissue Tears

The knee meniscus is a soft fibrous tissue with a high incidence of injury in older populations. The objective of this study was to determine the effect of age on the failure behavior of human knee meniscus when applying uniaxial tensile loads parallel or perpendicular to the primary circumferential fiber orientation. Two age groups were tested: under 40 and over 65 years old. We paired high-speed video with digital image correlation to quantify for the first time the planar strains occurring in the tear region at precise time points, including at ultimate tensile stress, when the tissue begins losing load-bearing capacity. On average, older meniscus specimens loaded parallel to the fiber axis had approximately one-third less ultimate tensile strain and absorbed 60% less energy to failure within the tear region than younger specimens (p \u3c 0.05). Older specimens also had significantly reduced strength and material toughness when loaded perpendicular to the fibers (p \u3c 0.05). These age-related changes indicate a loss of collagen fiber extensibility and weakening of the non-fibrous matrix with age. In addition, we found that when loaded perpendicular to the circumferential fibers, tears propagated near the planes of maximum tensile stress and strain. Whereas when loaded parallel to the circumferential fibers, tears propagated oblique to the loading axis, closer to the planes of maximum shear stress and strain. Our experimental results can assist the selection of valid failure criteria for meniscus, and provide insight into the effect of age on the failure mechanisms of soft fibrous tissue

Applying ASTM Standards to Tensile Tests of Musculoskeletal Soft Tissue: Methods to Reduce Grip Failures and Promote Reproducibility

Tensile testing is an essential experiment to assess the mechanical integrity of musculoskeletal soft tissues, yet standard test methods have not been developed to ensure the quality and reproducibility of these experiments. The ASTM International standards organization has created tensile test standards for common industry materials that specify geometric dimensions of test specimens (coupons) that promote valid failures within the gage section (midsubstance), away from the grips. This study examined whether ASTM test standards for plastics, elastomers, and fiber-reinforced composites are suitable for tensile testing of bovine meniscus along the circumferential fiber direction. We found that dumbbell (DB) shaped coupons based on ASTM standards for elastomers and plastics had an 80% and 60% rate of midsubstance failures, respectively. The rate of midsubstance failures dropped to 20% when using straight (ST) coupons based on ASTM standards for fiber-reinforced composites. The mechanical properties of dumbbell shaped coupons were also significantly greater than straight coupons. Finite element models of the test coupons revealed stress distributions that supported our experimental findings. In addition, we found that a commercial deli-slicer was able to slice meniscus to uniform layer thicknesses that were within ASTM dimensional tolerances. This study provides methods, recommendations, and insights that can advance the standardization of tensile testing in meniscus and other soft fibrous tissues

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health