Local Tissue Mechanics Research Articles

A Computed Microtomography Method for Understanding Epiphyseal Growth Plate Fusion.

The epiphyseal growth plate is a developmental region responsible for linear bone growth, in which chondrocytes undertake a tightly regulated series of biological processes. Concomitant with the cessation of growth and sexual maturation, the human growth plate undergoes progressive narrowing, and ultimately disappears. Despite the crucial role of this growth plate fusion “bridging” event, the precise mechanisms by which it is governed are complex and yet to be established. Progress is hindered by the current methods for growth plate visualization; these are invasive and largely rely on histological procedures. Here, we describe our non-invasive method utilizing synchrotron X-ray computed microtomography for the examination of growth plate bridging, which ultimately leads to its closure coincident with termination of further longitudinal bone growth. We then apply this method to a dataset obtained from a benchtop micro computed tomography scanner to highlight its potential for wide usage. Furthermore, we conduct finite element modeling at the micron-scale to reveal the effects of growth plate bridging on local tissue mechanics. Employment of these 3D analyses of growth plate bone bridging is likely to advance our understanding of the physiological mechanisms that control growth plate fusion.

Hybrid Ceramo-Polymeric Nanocomposite for Biomimetic Scaffolds Design and Preparation

Biomimetics, biomechanics and tissue engineering are three multidisciplinary fields that have been contemplated in this research to attain the objective of improving prosthetic implants reliability. Since testing and mathematical methods are closely interlaced, a promising approach seemed to be the combination of in vitro and in vivo experiments with computer simulations (in silico). An innovative biomimetics and biomechanics approach and new synthetic structure providing a microenvironment, which is mechanically coherent and nutrient conducive for tissue osteoblast cell cultures used in regenerative medicine, are presented. The novel hybrid ceramo-polymeric nanocomposites are mutually investigated by Finite Element Analysis (FEA) biomimetic modelling, anatomic reconstruction, quantitative-computed-tomography characterization, computer design of tissue scaffold. The starting base materials are a class of innovative highly bioactive hybrid ceramo-polymeric materials set-up by the proponent research group that will be used as bioactive matrix for the preparation of in situ bio-mineralised tecto-structured porous nanocomposites. This study treats biomimetics, biomechanics and tissue engineering as strongly correlated multidisciplinary fields combined to design bone tissue scaffolds. The growth, maintenance and ossification of bone are fundamental and are regulated by the mechanical cues that are imposed by physical activities: This biomimetical/biomechanical approach will be pursued in designing the experimental procedures for in vitro scaffold mineralization and ossification. Bio-tissue mathematical modelling serves as a central repository to interface design, simulation and tissue fabrication. Finite element computer analyses will be used to study the role of local tissue mechanics on endochondral ossification patterns, skeletal morphology and mandible thickness distributions using single and multi-phase continuum material representations of clinical cases of patients implanted with the traditional protocols. New protocols will be hypothesises for the use of the new biologically tecto-structured hybrid materials.

Pleural function and lymphatics

The pleural space plays an important role in respiratory function as the negative intrapleural pressure regimen ensures lung expansion and in the mean time maintains the tight mechanical coupling between the lung and the chest wall. The efficiency of the lung-chest wall coupling depends upon pleural liquid volume, which in turn reflects the balance between the filtration of fluid into and its egress out of the cavity. While filtration occurs through a single mechanism passively driving fluid from the interstitium of the parietal pleura into the cavity, several mechanisms may co-operate to remove pleural fluid. Among these, the pleural lymphatic system emerges as the most important one in quantitative terms and the only one able to cope with variable pleural fluid volume and drainage requirements. In this review, we present a detailed account of the actual knowledge on: (a) the complex morphology of the pleural lymphatic system, (b) the mechanism supporting pleural lymph formation and propulsion, (c) the dependence of pleural lymphatic function upon local tissue mechanics and (d) the effect of lymphatic inefficiency in the development of clinically severe pleural and, more in general, respiratory pathologies.

The mechanics of flexor tendon adhesions

The mechanics of adhesions at a local tissue level have not been extensively studied. This study compared microstrains and macrostrains in adhesions of immobilized and mobilized partially lacerated flexor digitorum profundus tendons in a New Zealand White rabbit model. At 2 weeks, 50 digits were randomized to either gross tensile testing or micromechanical assessment, in which the movement of fluorescently labelled cell nuclei, acting as dynamic markers, was visualized using real-time confocal microscopy. The structural stiffness and load at failure of immobilized adhesions were 140% and 160% of that of mobilized adhesions, respectively, and both differences were statistically significant. Micromechanically, different patterns of loading and failure were observed. Mobilized adhesions exhibited over a three-fold higher local strain, which was less uniformly distributed. Confocal microscopy provided an accurate measure of local strain. For the first time, it has been possible to visualize, define, and quantify local adhesion tissue mechanics. Mobilization appears to favour the formation of sites expressing increased local strain responses or those predisposed to heterogeneity and localized failure.

Modelling cartilage mechanobiology.

The growth, maintenance and ossification of cartilage are fundamental to skeletal development and are regulated throughout life by the mechanical cues that are imposed by physical activities. Finite element computer analyses have been used to study the role of local tissue mechanics on endochondral ossification patterns, skeletal morphology and articular cartilage thickness distributions. Using single-phase continuum material representations of cartilage, the results have indicated that local intermittent hydrostatic pressure promotes cartilage maintenance. Cyclic tensile strains (or shear), however, promote cartilage growth and ossification. Because single-phase material models cannot capture fluid exudation in articular cartilage, poroelastic (or biphasic) solid/fluid models are often implemented to study joint mechanics. In the middle and deep layers of articular cartilage where poroelastic analyses predict little fluid exudation, the cartilage phenotype is maintained by cyclic fluid pressure (consistent with the single-phase theory). In superficial articular layers the chondrocytes are exposed to tangential tensile strain in addition to the high fluid pressure. Furthermore, there is fluid exudation and matrix consolidation, leading to cell 'flattening'. As a result, the superficial layer assumes an altered, more fibrous phenotype. These computer model predictions of cartilage mechanobiology are consistent with results of in vitro cell and tissue and molecular biology experiments.

Measurement of surgically induced corneal deformations using three-dimensional confocal microscopy.

The goal of this study was to develop and apply a new set of experimental techniques for measuring the local deformations induced by partial-thickness corneal incisions in situ. Eight adult cat eyes were enucleated and cannulated, with corneal viability maintained as close to in vivo conditions as possible and intraocular pressure (IOP) carefully controlled. Experimental measurements were made pre/post radial keratotomy (RK) surgery in situ at IOPs of 15, 30, and 45 mm Hg. Incision depth and cross-sectional profiles were measured at the midpoint of selected incisions using three-dimensional (3-D) tandem scanning confocal microscopy (TSCM); central corneal curvature was estimated using a commercial corneal topographical analysis system, and corneal thickness was assessed by both 3-D TSCM and ultrasonic pachymetry. Corneas were then processed for light microscopy and incision depth was measured histologically. Finite element models were developed for comparison with the experimental measurements. There was no significant change in central corneal thickness (-5.3 +/- 3.9%, n = 8) over the course of the experiments, demonstrating that normal endothelial cell function and normal stromal hydration was maintained. The in situ TSCM incision depth measurements were significantly correlated with the histological measurements (slope = 0.95, R = 0.854, p < 0.01, n = 13 incisions). Measured incision gape at the top (anterior) of the stroma was 64.9 +/- 13.4, 87.3 +/- 12.6, and 108.7 +/- 14 microns at IOPs of 15, 30, and 45 mm Hg, respectively. The 3-D incision profiles were nonlinear in shape; comparison with the finite element models suggests that the shape of the wound profile may provide unique information regarding the shear stiffness of the cornea. Overall, the data suggest that TSCM measurements of the cross-sectional profile of the incisions immediately after RK under controlled in situ conditions provide important data regarding the mechanical behavior of the cornea after refractive surgery. These data should provide the foundation for future studies into the relationships between local tissue mechanics and corneal wound healing.