Elastic Stress Singularities: Implications for the Attachment of Tendon to Bone

The material mismatch at the attachment of tendon to bone is amongst the most severe for any tensile connection in nature. This is related to the large difference between the stiffness of tendon and bone, whose moduli of elasticity vary by two orders of magnitude. Predictably, such an abrupt change in the stiffness realized over a very narrow insertion site results in high local stresses. One of the implications of the stress distribution is a potential for stress singularities at the junction of the insertion to the bone.

Influence of Permeability on the Compressive Property of Articular Cartilage: A Scaffold-Free, Stem Cell-Based Therapy for Cartilage Repair

Since the healing capacity of articular cartilage is limited, it is important to develop cell-based therapies for the repair of cartilage. Although synthetic or animal-derived scaffolds are frequently used for effective cell delivery long-term safety and efficiency of such scaffolds still remain unclear. We have been studying on a scaffold-free tissue engineered construct (TEC) bio-synthesized from synovium-derived mesenchymal stem cells (MSCs) [1]. As the TEC specimen is composed of cells with their native extracellular matrix, we believe that it is free from concern regarding long term immunological effects. our previous studies indicated that a porcine partial thickness chondral defect was successfully repaired with TEC but that the compressive property of the TEC-treated cartilage-like repaired tissue was different from normal cartilage in both immature and mature animals. Imura et al. found that the permeability of the immature porcine cartilage-like tissues repaired with TEC recovered to normal level for 6 months except the superficial layer [2]. Therefore, the present study was performed to determine the depth-dependent permeability of mature porcine cartilage-like tissue repaired with TEC. Moreover, we investigated the effect of difference of permeability on the compressive property of articular cartilage using a finite element analysis (FEM).

Estimation of Left Ventricular Wall Stiffness by Analysis of Late Diastolic Pressure Components

Left ventricular diastolic dysfunction (LVDD) is any abnormality in the filling of the left ventricle and is conventionally evaluated by analysis of the relaxation driven phase, or early diastole. LVDD has been shown to be a precursor to heart failure and the diagnosis and treatment for diastolic failure is less understood than for systolic failure. Diastole consists of two filling waves, early and late and is primarily dependent on ventricular relaxation and wall stiffness.

Echocardiography Evaluation of a Novel Stable Ovine Heart Failure Model Suitable for Cardiovascular Device Testing

Numerous large animal models of chronic cardiac ischemia have been developed to explore either pathological mechanisms and or device interventions in developed heart failure models. Traditionally chronic heart failure in large animal models such as sheep or pigs has been induced by either coronary ligation with or without reperfusion. Coronary ligation is often attempted in the open chest surgical model or more recently in the closed chest animal via angiography [1]. Both techniques can be challenging and also induce high mortality with the risk of myocardial stunning and resultant shock and or lethal arrhythmias. There is also difficulty in developing stable heart failure across cases where infarct sizes can be variable. One strategy to over come this variability has been via rapid ventricular pacing, however inducing heart failure does not induce sustained heart failure in many cases if the pacing is switched off, and additionally pacing does not induce some of the underlying pathology seen in the development of heart failure [1].

Effects of Passaging on the Migration Response of Synovium-Derived Stem Cells to an Applied DC Electric Field

Strategies for cartilage tissue engineering and repair have recently focused on cell sources from the surrounding joint tissue as an alternative to chondrocytes. Synovium-derived stem cells (SDSCs) are found in the intimal layer of the synovium, the thin overlying capsule surrounding the joint space [1] and have been found to exhibit a greater chondrogenic potential than stem cells from other origins such as bone marrow stem cells or adipose derived stem cells [2–4]. Under directed cues, these cells have been shown to be capable of migrating from the synovium membrane into articular cartilage defects, though the mechanism behind such movement is unclear. As a first step, we have previously shown that SDSCs expanded in 2D monolayer culture in a growth factor cocktail of TGF-β1, FGF, and PDGF-ββ exhibit directed cathodal migration with perpendicular alignment when under the influence of an applied DC electric field [5]. As cellular behavior and response to an external stimulus can change with exposure to growth factors and passage number, we look here to characterize the effects of passaging on the migration response of SDSCs to an applied electric field. We hypothesize that if these cells develop more chondrocyte-like characteristics with growth factor passaging, their response will mimic that which has previously been reported for chondrocytes, notably directed cathodal (negative pole) migration and perpendicular realignment of the long axis to the direction of applied field [6].

An Automated Histologic System for 3D Histomorphometry of the Mouse Knee

Osteoarthritis (OA) is a degenerative joint disease that is a leading cause of adult pain and disability in Western countries1. Clinically, several structural features of the joint are important in diagnosis, prognosis and evaluation of treatment efficacy, e.g. cartilage volume, homogeneity and joint space narrowing2,3. In animal models of OA, structural features such as bone defects and cartilage changes are commonly investigated using histomorphometry, a technique that uses stereological point counting and manual tracing of regions of interest to extract 3-dimensional (3D) geometrical properties from 2D histology slides. This is time-consuming and subject to inter-observer variations, hence limiting precision 4,5. Therefore, a technique for rapidly imaging joint structures in 3D at high resolution, including articular cartilage and subchondral bone, is currently needed in pre-clinical OA research.

A Nanoindentation Method for Hydrated Compliant Materials

Nanoindentation is becoming an increasingly popular tool in the biomaterials field due to its ability to measure local mechanical properties in small, irregularly-shaped or heterogeneous samples.1 Although this technique was readily adapted to the study of mineralized tissues, the application of nanoindentation to compliant, hydrated biomaterials such as soft tissues and hydrogels has led to many challenges.1 Three key concerns associated with nanoindentation of compliant, hydrated materials are inaccurate surface detection, errors due to adhesion forces, and fluid interactions with the tip.1–4

The Effect of Muscle Loading on Internal Mechanical Parameters of the Lumbar Spine: A Finite Element Study

The human spine experiences complex loading in vivo; however, simplifications to these loading conditions are commonly made in computational and experimental protocols. Pure moments are often used in cadaveric preparations to replicate in vivo loading conditions, and previous studies have shown this method adequately predicts range of motion behavior (1, 2). It is unclear what effect pure moment loading has on the tissue-level internal mechanical parameters such as stresses in the annulus fibrosus and facet contact parameters. Recent advances in musculoskeletal modeling have elucidated previously unknown quantities of the musculature recruitment patterns such as times, forces, and directions. The advancements are especially relevant in cases of surgical intervention because the spinal musculature has been reported to play a critical role in providing additional stability to the spine when defects such as discectomy and nucleotomy are involved (2). Thus, the aim of the study was to determine the importance of computational loading conditions on the resultant global ranges of motion, as well as the tissue-level predictions of annulus fibrosus stresses, and facet contact pressures, forces, and areas.

Patient-Specific Modelling of Intracranial Aneurysm Evolution

Intracranial aneurysms appear as sac-like outpouchings of the cerebral vasculature wall; inflated by the pressure of the blood that fills them. They are relatively common and affect up to 5% of the adult population. Fortunately, most remain asymptomatic. However, there is a small but inherent risk of rupture: 0.1% to 1% of detected aneurysms rupture every year. If rupture does occur there is a 30% to 50% chance of fatality. Consequently, if an aneurysm is detected, clinical intervention may be deemed appropriate. Therapy is currently aimed at pre-rupture detection and preventative treatment. However, interventional procedures are not without risk to the patient. The improvement and optimization of interventional techniques is an important concern for patient welfare and is necessary for rationalisation of healthcare priorities. Hence there is a need to develop methodologies to assist in identifying those ICAs most at risk of rupture. We focus on the mathematical modelling and computational simulation of ICA evolution. Models must take into consideration: (i) the biomechanics of the arterial wall; (ii) the biology of the arterial wall and (iii) the complex interplay between (i) and (ii), i.e. the mechanobiology of the arterial wall. The ultimate ambition of such models is to aid clinical diagnosis on a patient-specific basis. However, due to the significant biological complexity coupled with limited histological information such models are still in their relative infancy. Current research focuses on simulating the evolution of an ICA with an aim to yield insight into the growth and remodelling (G&R) processes that give rise to inception, enlargement, stabilisation and rupture. We present a novel Fluid-Structure-Growth computational framework for modelling aneurysm evolution.

Modeling the Inflation Response of C57BL/6 Mouse Sclera

Small rodent models have become increasingly useful to investigate how the mechanical properties of soft tissues may influence disease development. These animal models allow access to aged, diseased, or genetically-altered tissue samples, and through comparisons with wild-type or normal tissue it can be explored how each of these variables influence tissue function. The challenges to deriving meaningful material parameters for these small tissue samples include designing physiologically-relevant mechanical testing protocols and interpreting the experimental load-displacement data in an appropriate constitutive framework to quantify material parameters. This study was motivated by determining the possible role of scleral material properties in the development of glaucomatous damage to the retinal ganglion cells (RGC). Glaucoma is one of the leading causes of blindness in the United States and in the world with an estimate of 60 million people affected by this year [1]. Through exploring mouse models, the overall goal of our work is to determine the role of scleral material properties and scleral tissue microstructure in the pathogenesis of glaucoma.