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Biomedical subjects

Guy M Genin

Publications and source records attributed to Guy M Genin.

8 recordsLinked to original sources

Cellular and matrix contributions to tissue construct stiffness increase with cellular concentration.

The mechanics of bio-artificial tissue constructs result from active and passive contributions of cells and extracellular matrix (ECM). We delineated these for a fibroblast-populated matrix (FPM) consisting of chick embryo fibroblast cells in a type I collagen ECM through mechanical testing, mechanical modeling, and selective biochemical elimination of tissue components. From a series of relaxation tests, we found that contributions to overall tissue mechanics from both cells and ECM increase exponentially with the cell concentration. The force responses in these relaxation tests exhibited a logarithmic decay over the 3600 second test duration. The amplitudes of these responses were nearly linear with the amplitude of the applied stretch. The active component of cellular forces rose dramatically for FPMs containing higher cell concentrations.

Animals↗

In vivo imaging of rapid deformation and strain in an animal model of traumatic brain injury.

In traumatic brain injury (TBI) rapid deformation of brain tissue leads to axonal injury and cell death. In vivo quantification of such fast deformations is extremely difficult, but important for understanding the mechanisms of degeneration post-trauma and for development of numerical models of injury biomechanics. In this paper, strain fields in the brain of the perinatal rat were estimated from data obtained in vivo during rapid indentation. Tagged magnetic resonance (MR) images were obtained with high spatial (0.2 mm) and temporal (3.9 ms) resolution by gated image acquisition during and after impact. Impacts were repeated either 64 or 128 times to obtain images of horizontal and vertical tag lines in coronal and sagittal planes. Strain fields were estimated by harmonic phase (HARP) analysis of the tagged images. The original MR data was filtered and Fourier-transformed to obtain HARP images, following a method originally developed by Osman et al. (IEEE Trans. Med. Imaging 19(3) (2000) 186). The displacements of material points were estimated from intersections of HARP contours and used to generate estimates of the deformation gradient and Lagrangian strain tensors. Maximum principal Lagrangian strains of >0.20 at strain rates >40/s were observed during indentations of 2 mm depth and 21 ms duration.

Animals↗

On the application of strain factors for approximation of the contribution of anisotropic cells to the mechanics of a tissue construct.

Bio-artificial tissue constructs consisting of fibroblast cells embedded in a collagenous matrix are valuable in vitro systems in which to study cellular mechanics. Deriving cellular mechanics from the results of experimentation on tissue constructs requires a mathematical relationship that delineates amongst the contributions of the constituents of a tissue construct. A scaling between the average strain in a uniformly stretched tissue and the axial strain in isotropic cells was used in earlier work to study relations between cell mechanics and the overall mechanics of a tissue construct. That work showed that a scaling factor called a "strain factor" provided an accurate representation of the average axial strain in isotropic cells. The present study analyzes such relationships for anisotropic cells. We incorporate Eshelby's (1957; Proceedings of the Royal Society of London A 241, 376; 1959; Proceedings of the Royal Society of London A 252, 561) exact solution for the strain field in isolated ellipsoidal inclusions into the Zahalak (Biophysical journal 79, 2369) constitutive model for tissue constructs. Results showed that, for the case of prolate cells, the strain along the major cell axis is mostly influenced by the remote strain projected along that axis; off-axis cell mechanics plays only a small role in most tissues. The strain factor approximation is shown to be accurate for anisotropic cells to within a few percent for the vast majority of tissues. The results presented in this paper provide an explicit measure of the effects of cellular anisotropy, and a mechanism for calculating the contributions of these effects to overall tissue mechanics when these effects are important.

Anisotropy↗

Collagen fiber orientation at the tendon to bone insertion and its influence on stress concentrations.

The tendon to bone insertion serves the mechanical role of transferring loads from a relatively compliant tendon to a relatively rigid bone. The details of the mechanism of load transfer are of great importance, since current surgical procedures for tendon reattachment have high failure rates. We hypothesized that the microscopic structure of the insertion is optimized to minimize stress concentrations associated with this load transfer. To explore this, collagen fiber orientation distributions were measured in the supraspinatus tendons of rats. The angular deviation of fibers was fairly uniform across the insertion, and the mean angles of the local distributions deviated mildly from the tendon axis. To explore how these observed property distributions could influence load transfer, these distributions were used to derive material properties for an idealized two-dimensional mechanical model of an insertion. Comparison between stress concentrations in this idealized model and those in three comparison models suggests that the microstructure serves to (1) simultaneously reduce stress concentrations and material mass, and (2) shield the insertion's outward splay from the highest stresses.

Animals↗

Thin bio-artificial tissues in plane stress: the relationship between cell and tissue strain, and an improved constitutive model.

Constitutive models are needed to relate the active and passive mechanical properties of cells to the overall mechanical response of bio-artificial tissues. The Zahalak model attempts to explicitly describe this link for a class of bio-artificial tissues. A fundamental assumption made by Zahalak is that cells stretch in perfect registry with a tissue. We show this assumption to be valid only for special cases, and we correct the Zahalak model accordingly. We focus on short-term and very long-term behavior, and therefore consider tissue constituents that are linear in their loading response (although not necessarily linear in unloading). In such cases, the average strain in a cell is related to the macroscopic tissue strain by a scalar we call the "strain factor". We incorporate a model predicting the strain factor into the Zahalak model, and then reinterpret experiments reported by Zahalak and co-workers to determine the in situ stiffness of cells in a tissue construct. We find that, without the modification in this article, the Zahalak model can underpredict cell stiffness by an order of magnitude.

Animals↗

The relationship between cell and tissue strain in three-dimensional bio-artificial tissues.

Continuum constitutive laws are needed to ensure that bio-artificial tissue constructs replicate the mechanical response of the tissues they replace, and to understand how the constituents of these constructs contribute to their overall mechanical response. One model designed to achieve both of these aims is the Zahalak model, which was modified by Marquez and co-workers to incorporate inhomogeneous strain fields within very thin tissues. When applied to reinterpret previous measurements, the modified Zahalak model predicted higher values of the continuum stiffness of fibroblasts than earlier estimates. In this work, we further modify the Zahalak model to account for inhomogeneous strain fields in constructs whose cell orientations have a significant out-of-plane component. When applied to reinterpret results from the literature, the new model shows that estimates of continuum cell stiffness might need to be revised upward. As in this article's companion, we updated the average cell strain by defining a correction factor ("strain factor"), based upon the elastic response. Three different cell orientation distributions were studied. We derived an approximate scaling model for the strain factor, and validated it against exact and self-consistent (mean-field) solutions from the literature for dilute cell concentrations, and Monte Carlo simulations involving three-dimensional finite element analyses for high cell concentrations.

Animals↗

Incremental mechanics of collagen gels: new experiments and a new viscoelastic model.

Paired incremental uniaxial step (i.e., relaxation) and ramp tests were conducted simultaneously on four (nominally) identical samples of type I collagen gel, over a direct strain range 0 < epsilon < 0.2. The paired step and ramp responses could not both be predicted by a simple viscoelastic constitutive relation (either linear or Fung-type), but could be predicted reasonably accurately by a general nonlinear viscoelastic relation with a strain-dependent relaxation spectrum, of the form sigma(t) = f(t)-infinity g(t-tau,epsilon)[d(epsilon)(tau)/d(tau)]d(tau). Based on a four-term exponential-series approximation, we measured the stiffness moduli and time constants of the relaxation function, g(t,epsilon), for the four gel samples that we tested, and found that the time constants were independent of strain but the moduli increased strongly with strain. Further, we found that the time constants did not vary across the four gels, but the moduli varied by a factor of about 2 across the gels. Some additional tests show features of the response of collagen gels to cycles of application and removal of loading.

Biocompatible Materials↗

Linear and angular head accelerations during heading of a soccer ball.

PURPOSE: Cognitive deficits observed in professional soccer players may be related to heading of a soccer ball. To assess the severity of a single instance of heading a soccer ball, this study experimentally and theoretically evaluated the linear and angular accelerations experienced by the human head during a frontal heading maneuver. METHODS: Accelerations were measured using a set of three triaxial accelerometers mounted to the head of each of four adult male subjects. These measurements (nine signals) were used to estimate the linear acceleration of the mass center and the angular acceleration of the head. Results were obtained for ball speeds of 9 and 12 m.s(-1) (approximately 20 and 26 mph). A simple mathematical model was derived for comparison. RESULTS: At 9 m.s(-1), peak linear acceleration of the head was 158 +/- 19 m.s(-2) (mean +/- standard deviation) and peak angular acceleration was 1302 +/- 324 rad.s(-2); at 12 m.s(-1), the values were 199 +/- 27 m.s-2 and 1457 +/- 297 rad.s-2, respectively. The initial acceleration pulses lasted approximately 25 ms. Measured head accelerations confirmed laboratory headform measurements reported in the literature and fell within the ranges predicted by the theoretical model. CONCLUSIONS: Linear and angular acceleration levels for a single heading maneuver were well below those thought to be associated with traumatic brain injury, as were computed values of the Gadd Severity Index and the Head Injury Criterion. However, the effect of repeated acceleration at this relatively low level is unknown.

Acceleration↗