Hyperelastic properties of human meniscal attachments

Meniscal attachments are ligamentous tissues anchoring the menisci to the underlying subchondral bone. Currently little is known about the behavior of meniscal attachments, with only a few studies quantitatively documenting their properties. The objective of this study was to quantify and compare the tensile mechanical properties of human meniscal attachments in the transverse direction, curve fit experimental Cauchy stress-stretch data to evaluate the hyperelastic behavior, and couple these results with previously obtained longitudinal data to generate a more complete constitutive model. Meniscal attachment specimens were tested using a uniaxial tension test with the collagen fibers oriented perpendicular to the loading axis. Tests were run until failure and load-optical displacement data was recorded for each test. The medial posterior attachment was shown to have a significantly greater elastic modulus (6.42±0.78 MPa) and ultimate stress (1.73±0.32 MPa) when compared to the other three attachments. The Mooney-Rivlin material model was selected as the best fit for the transverse data and used in conjunction with the longitudinal data. A novel computational approach to determining the transition point between the toe and linear regions is presented for the hyperelastic stress-stretch curves. Results from piece-wise non-linear longitudinal curve fitting correlate well with previous linear elastic and SEM findings. These data can be used to advance the design of meniscal replacements and improve knee joint finite element models.     

Failure properties and strain distribution analysis of meniscal attachments

The menisci are frequently injured due to both degeneration and traumatic tearing. It has been suggested that the success of a meniscal replacement is dependent on several factors, one of which is the secure fixation and firm attachment of the replacement to the tibial plateau. Therefore, the objectives of the current study were to (1) determine the failure properties of the meniscal horn attachments, and (2) determine the strain distribution over their surfaces. Eight bovine knee joints were used to study the mechanical response of the meniscal attachments. Three meniscal attachments from one knee of each animal were tested in uniaxial tension at 2%/s to determine the load deformation response. During the tests, the samples were marked and local strain distributions were determined with a video extensometer. The linear modulus of the medial anterior attachment (154+/-134 MPa) was significantly less than both the medial posterior (248+/-179 MPa, p=0.0111) and the lateral anterior attachment (281+/-214 MPa, p=0.0007). Likewise, the ultimate strain for the medial anterior attachments (13.5+/-8.8%) was significantly less than the medial posterior (23+/-13%, p<0.0001) and the lateral anterior attachment (20.3+/-11.1%, p=0.0033). There were no significant differences in the structural properties or ultimate stress between the meniscal attachments (p>0.05). No significant differences in ultimate strain or moduli across the surface of the attachments were noted. Based on the data obtained, a meniscal replacement would need different moduli for each of the different attachments. However, the attachments appear to be homogeneous.     

Sensitivities of medial meniscal motion and deformation to material properties of articular cartilage, meniscus and meniscal attachments using design of experiments methods

This study investigated the role of the material properties assumed for articular cartilage, meniscus and meniscal attachments on the fit of a finite element model (FEM) to experimental data for meniscal motion and deformation due to an anterior tibial loading of 45 N in the anterior cruciate ligament-deficient knee. Taguchi style L18 orthogonal arrays were used to identify the most significant factors for further examination. A central composite design was then employed to develop a mathematical model for predicting the fit of the FEM to the experimental data as a function of the material properties and to identify the material property selections that optimize the fit. The cartilage was modeled as isotropic elastic material, the meniscus was modeled as transversely isotropic elastic material, and meniscal horn and the peripheral attachments were modeled as noncompressive and nonlinear in tension spring elements. The ability of the FEM to reproduce the experimentally measured meniscal motion and deformation was most strongly dependent on the initial strain of the meniscal horn attachments (epsilon(1H)), the linear modulus of the meniscal peripheral attachments (E(P)) and the ratio of meniscal moduli in the circumferential and transverse directions (E(theta)E(R)). Our study also successfully identified values for these critical material properties (epsilon(1H) = -5%, E(P) = 5.6 MPa, E(theta)E(R) = 20) to minimize the error in the FEM analysis of experimental results. This study illustrates the most important material properties for future experimental studies, and suggests that modeling work of meniscus, while retaining transverse isotropy, should also focus on the potential influence of nonlinear properties and inhomogeneity.     

How the stiffness of meniscal attachments and meniscal material properties affect tibio-femoral contact pressure computed using a validated finite element model of the human knee joint

In an effort to prevent degeneration of articular cartilage associated with meniscectomies, both meniscal allografts and synthetic replacements are subjects of current interest and investigation. The objectives of the current study were to (1) determine whether a transversely isotropic, linearly elastic, homogeneous material model of the meniscal tissue is necessary to achieve a normal contact pressure distribution on the tibial plateau, (2) determine which material and boundary condition (attachments) parameters affect the contact pressure distribution most strongly, and (3) set tolerances on these parameters to restore the contact pressure distribution to within a specified error. To satisfy these objectives, a finite element model of the tibio-femoral joint of a human cadaveric knee (including both menisci) was used to study the contact pressure distribution on the tibial plateau. To validate the model, the contact pressure distribution on the tibial plateau was measured experimentally in the same knee used to create the model. Within physiologically reasonable bounds on five material parameters and four attachment parameters associated with a meniscal replacement, an optimization was performed under 1200 N of compressive load on the set of nine parameters to minimize the difference between the experimental and model results. The error between the experimental and model contact variables was minimized to 5.4%. The contact pressure distribution of the tibial plateau was sensitive to the circumferential modulus, axial/radial modulus, and horn stiffness, but relatively insensitive to the remaining six parameters. Consequently, both the circumferential and axial/radial moduli are important determinants of the contact pressure distribution, and hence should be matched in the design and/or selection of meniscal replacements. In addition, during surgical implantation of a meniscal replacement, the horns should be attached with high stiffness bone plugs, and the attachments of the transverse ligament and deep medial collateral ligament should be restored to minimize changes in the contact pressure distribution, and thereby possibly prevent the degradation of articular cartilage.     

Nanoindentation of human meniscal surfaces

Menisci are crescent shaped fibrocartilaginous structures which support load distribution of the knee. The menisci are specifically designed to fit the contour of the femoral condyles, aiding to disperse the stresses on the tibial plateau and in turn safeguarding the underlying articular cartilage. The importance of the meniscal superficial layer has not been fully revealed and it is suspected that this layer plays a pivotal role for meniscal function. In this study, both femoral (proximal) and tibial (distal) contacting meniscal surfaces were mechanically examined on the nano-level among three distinct regions (anterior, central and posterior) of the lateral and medial menisci. Nanoindentation testing showed no significant differences among regions, surfaces or anatomical locations, possibly elucidating on the homogeneity of the meniscal superficial zone structure (E(instantaneous): 3.17-4.12MPa, E(steady-state): 1.47-1.69MPa). Nanomechanical moduli values were approximately an order of magnitude greater than micro-scale testing derived moduli values. These findings validate the structural homogeneity of the meniscal superficial zone, showing that material properties are statistically similar regardless of meniscal surface and region. Understanding the mechanical behavior of meniscal surfaces is imperative to properly design an effective meniscal replacement.     

Geometry of actin-membrane attachments in the smooth muscle cell: the localisations of vinculin and alpha-actinin.

Antibodies to vinculin, a component of actin-membrane attachment sites, revealed by immunofluorescence microscopy a parallel co-axial array of continuous rib-like bands on the surface of isolated vertebrate smooth muscle cells. Images of extended and shortened cells showed that these ribs remain co-axially organised on contraction. Reference to earlier studies and labelling of thin sections indicates that the ribs correspond in position to the adhesion plaques previously described in electron microscope studies. Alpha-actinin showed a punctate distribution consistent with its presence in the cytoplasmic dense bodies, but did not show a constant association with the vinculin-containing ribs. It is suggested that alpha-actinin is an intracellular actin linker and not membrane associated, as earlier supposed, and that vinculin is, as deduced by others, a mediator of actin membrane attachment. The apparent co-association of these two proteins, noted previously, is concluded to arise from the inevitable geometrical apposition of peripheral and pre-terminal parts of the contractile machinery with the cell membrane.     

Geometry and respiratory displacement of human ribs

The three-dimensional coordinates of points in the ribs of two supine relaxed males, holding their breath at functional residual capacity (FRC) and with their glottis closed at total lung capacity (TLC), were obtained from volumetric X-ray computed tomographical images. The orientation of planes that best fit the data for each rib at each lung volume and the circular arcs that fit the points in the planes of the ribs were determined, and average values of these geometrical parameters for ribs 3-7 are reported. The planes of the ribs at TLC can be described as displaced from the planes at FRC by a rotation about an axis that passes near the spine. The pump handle and bucket handle components of rotation are 11 and 13 degrees, respectively, for rib 3 and both decrease with increasing rib number to 7 and 10 degrees at rib 7. The angles between the axes of rotation and the midplane are approximately 35 degrees for all 5 ribs. The radii of the circular arcs fit to the data at TLC are slightly larger than those at FRC, and this suggests that there is a small component of rotation normal to the plane of the rib.     

Three-dimensional culture of human meniscal cells: Extracellular matrix and proteoglycan production

Background  

The meniscus is a complex tissue whose cell biology has only recently begun to be explored. Published models rely upon initial culture in the presence of added growth factors. The aim of this study was to test a three-dimensional (3D) collagen sponge microenvironment (without added growth factors) for its ability to provide a microenvironment supportive for meniscal cell extracellular matrix (ECM) production, and to test the responsiveness of cells cultured in this manner to transforming growth factor-β (TGF-β).     

Regional distribution of wall thickness and failure properties of human abdominal aortic aneurysm

The regional distribution of wall thickness and failure properties in human abdominal aortic aneurysm (AAA) was explored. Three unruptured and one ruptured AAA were harvested as a whole during necropsy. Thickness was measured at about every 1.5 cm² wall surface area for an average of 100 measurement sites per AAA. Multiple longitudinally oriented rectangular specimen strips were cut at various locations from each AAA for a total of 48 strips. The strips were subjected to uniaxial extension until failure. Wall thickness varied regionally and between AAA from as low as 0.23 mm at a rupture site to 4.26 mm at a calcified site (median=1.48 mm). Wall thickness was slightly lower in the posterior and right regions. The failure tension (ultimate) of specimen strips varied regionally and between AAA from 5.5 N/cm close to a blister site in the ruptured AAA to 42.3 N/cm at the undilated neck of a 4 cm diameter unruptured AAA (median=14.8 N/cm). Failure stress (ultimate) varied from 33.6 to 235.1 N/cm² (median=126.6 N/cm²). There was no perceptible pattern in failure properties along the circumference. Failure tension of specimen strips at or close to blisters was mostly low. The rupture site in the ruptured aneurysm had the lowest recorded wall thickness of 0.23 mm with only slightly higher readings within a 1 cm radius. The failure tension of the specimen strip close to the rupture site was low (11.1 N/cm) compared to its neighborhood in the ruptured aneurysm.     

Checkpoint-independent stabilization of kinetochore-microtubule attachments by Mad2 in human cells

Faithful chromosome segregation is required for cell and organism viability and relies on both the mitotic checkpoint and the machinery that corrects kinetochore-microtubule (k-MT) attachment errors. Most solid tumors have aneuploid karyotypes and many missegregate chromosomes at high rates in a phenomenon called chromosomal instability (CIN). Mad2 is essential for mitotic checkpoint function and is frequently overexpressed in human tumors that are CIN. For unknown reasons, cells overexpressing Mad2 display high rates of lagging chromosomes. Here, we explore this phenomenon and show that k-MT attachments are hyperstabilized by Mad2 overexpression and that this undermines the efficiency of correction of k-MT attachment errors. Mad2 affects k-MT attachment stability independently of the mitotic checkpoint because k-MT attachments are unaltered upon Mad1 depletion and Mad2 overexpression hyperstabilizes k-MT attachments in Mad1-deficient cells. Mad2 mediates these effects with Cdc20 by altering the centromeric localization and activity of Aurora B kinase, a known regulator of k-MT attachment stability. These data reveal a new function for Mad2 to stabilize k-MT attachments independent of the checkpoint and explain why Mad2 overexpression increases chromosome missegregation to cause chromosomal instability in human tumors.     

Geometry, thermodynamics, and protein

We derive a new continuous free energy formula for protein folding. We obtain the formula first by adding hydrophobic effect to a classical free energy formula for cavities in water. We then obtain the same formula by geometrically pursuing the structure that fits best the well-known global geometric features of native structures of globular proteins: 1. high density; 2. small surface area; 3. hydrophobic core; 4. forming domains for long polypeptide chains. Conformations of a protein are presented as an all atom CPK model where each atom is a ball B(x_i,r_i). All conformations satisfy generally defined steric conditions. For each conformation P of a globular protein, there is a closed thermodynamic system Ω_P⊃P bounded by the molecular surface M_P. Both methods derive the same free energy aV(P)+bA(P)+cW(P), where a,b,c>0, V(P), A(P), and W(P) are volume of Ω_P, area of M_P, and area of the hydrophobic surface W_P⊂M_P, which quantifies hydrophobic effect.Minimizing W(P) is sufficient to produce statistically significant native like secondary structures and hydrogen bonds in the proteins we simulated.     

The assessment of time-dependent changes in human performance.

This paper discribes a series of experiments to illustrate the use of various methods of time series analysis in the delineation of the effects of circadian and ultradian cycles on human performance. These experiments are concerned with measures of both human performance and physiology. They illustrate how the parameters of these time series analytic techniques can be used to postulate physiological mechanisms where time-dependent changes have been shown to be significant. The use of analytic techniques in both the time and frequency domain is illustrated.     

Interleukin-1, tumor necrosis factor-alpha,and transforming growth factor-beta 1 and integrative meniscal repair: influences on meniscal cell proliferation and migration

Introduction  

Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-β1 (TGF-β1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-α suppress, while TGF-β1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair.     

Geometry of human ribs pertinent to orthopedic chest-wall reconstruction

Orthopedic reconstruction of blunt chest trauma can aid restoration of pulmonary function to reduce the mortality associated with serial rib fractures and flail chest injuries. Contemporary chest wall reconstruction requires contouring of generic plates to the complex surface geometry of ribs. This study established a biometric foundation to generate specialized, anatomically contoured osteosynthesis hardware for rib fracture fixation. On human cadaveric ribs three through nine, the surface geometry pertinent to anatomically conforming osteosynthesis plates was characterized by quantifying the apparent rib curvature C(A), the longitudinal twist alpha(LT) along the diaphysis, and the unrolled curvature C(U). In addition, the rib cross-sectional geometry pertinent to intramedullary fixation strategies was characterized in terms of cross-section height, width, area, and cortex thickness. The rib surface exhibited a curvature C(A) ranging from 3.8 m(-1) in the anteromedial section of rib seven to 17.3 m(-1) in the posterior section of rib three. All ribs had in common a longitudinal twist alpha(LT), ranging from 41-60 degrees. The unrolled curvature C(U) decreased gradually from ribs three to five, and increased gradually with reversed orientation from rib six to nine. The cross-sectional area remained constant along the rib diaphysis. However, the medullary canal increased in size from 29.9 mm(2) posteriorly to 41.2 mm(2) in anterior rib segments. Results of this biometric rib characterization describe a novel strategy for intraoperative plate contouring and provide a foundation for the development of specialized rib osteosynthesis strategies.     

The attachments of the lateral and medial ends of the extensor retinaculum of the human wrist

The attachments of the lateral and medial ends of the extensor retinaculum of the human wrist were observed in 52 human upper limbs (from 26 cadavers) by dissection. In all the specimens used in this study, the lateral end of the retinaculum was found to be attached to the distal part of the anterior border of the radius and its medial end was attached to the styloid process of the ulna, the pisiform and the triquetrum.