A Short History of Bioengineering Research in Ireland.

In July 2018, Ireland will host the World Congress of Biomechanics in Dublin. This Congress is held once every 4 yr and is the premier meeting worldwide in its field, with over 3000 people expected to visit Dublin in July. The awarding of the 2018 Congress to Ireland is a reflection of the strength of biomechanics and bioengineering research in this country.

Aging enhances the vulnerability of mesenchymal stromal cells to uniaxial tensile strain-induced apoptosis.

Mechanical priming can be employed in tissue engineering strategies to control the fate and differentiation pattern of mesenchymal stromal cells. This is relevant to regenerative medicine whereby mechanical cues can promote the regeneration of a specific tissue type from mesenchymal precursors. The ability of cells to respond to mechanical forces is dependent upon mechanotransduction pathways that involve membrane-associated proteins, such as integrins.

Four decades of finite element analysis of orthopaedic devices: where are we now and what are the opportunities?

Finite element has been used for more than four decades to study and evaluate the mechanical behaviour total joint replacements. In Huiskes seminal paper "Failed innovation in total hip replacement: diagnosis and proposals for a cure", finite element modelling was one of the potential cures to avoid poorly performing designs reaching the market place. The size and sophistication of models has increased significantly since that paper and a range of techniques are available from predicting the initial mechanical environment through to advanced adaptive simulations including bone adaptation, tissue differentiation, damage accumulation and wear.

Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways.

Background: Mechanical stimulation is necessary for regulating correct formation of the skeleton. Here we test the hypothesis that mechanical stimulation of the embryonic skeletal system impacts expression levels of genes implicated in developmentally important signalling pathways in a genome wide approach. We use a mutant mouse model with altered mechanical stimulation due to the absence of limb skeletal muscle (Splotch-delayed) where muscle-less embryos show specific defects in skeletal elements including delayed ossification, changes in the size and shape of cartilage rudiments and joint fusion.

Acute appendicitis: investigating an optimal outer appendiceal diameter cut-point in a pediatric population.

Background: Acute appendicitis is the most common cause of abdominal pain in children requiring operative intervention. Among a number of sonographic criteria to aid in the diagnosis of appendicitis, an outer diameter >6 mm is the most objective and widely accepted. However, there is a lack of evidence-based standards governing this consensus.

Effect of membrane stiffness and cytoskeletal element density on mechanical stimuli within cells: an analysis of the consequences of ageing in cells.

A finite element model of a single cell was created and used to compute the biophysical stimuli generated within a cell under mechanical loading. Major cellular components were incorporated in the model: the membrane, cytoplasm, nucleus, microtubules, actin filaments, intermediate filaments, nuclear lamina and chromatin. The model used multiple sets of tensegrity structures.

A probabilistic modelling scheme for analysis of long-term failure of cemented femoral joint replacements.

Reliable prediction of long-term medical device performance using computer simulation requires consideration of variability in surgical procedure, as well as patient-specific factors. However, even deterministic simulation of long-term failure processes for such devices is time and resource consuming so that including variability can lead to excessive time to achieve useful predictions. This study investigates the use of an accelerated probabilistic framework for predicting the likely performance envelope of a device and applies it to femoral prosthesis loosening in cemented hip arthroplasty.

Corroboration of computational models for mechanoregulated stem cell differentiation.

Do computational models contribute to progress in mechanobiology? Jacobs and Kelly (in Advances on Modelling in Tissue Engineering, p. 1-14, 2011) suggest that they do, but at the same time propose a limitation in the form of the 'paradox of validation', whereby the information needed to validate mechanoregulation theories obviates the need for them in the first place. In this article, the corroboration of theories describing mechanoregulation of tissue differentiation is reviewed.

Application of a mechanobiological simulation technique to stents used clinically.

Many cardiovascular diseases are characterised by the restriction of blood flow through arteries. Stents can be expanded within arteries to remove such restrictions; however, tissue in-growth into the stent can lead to restenosis. In order to predict the long-term efficacy of stenting, a mechanobiological model of the arterial tissue reaction to stress is required.

The emergence of mechanoregulated endochondral ossification in evolution.

The differentiation of skeletal tissue phenotypes is partly regulated by mechanical forces. This mechanoregulatory aspect of tissue differentiation has been the subject of many experimental and computational investigations. However, little is known about what factors promoted the emergence of mechanoregulated tissue differentiation in evolution, even though mechanoregulated tissue differentiation, for example during development or healing of adult bone, is crucial for vertebrate phylogeny.

Being a hospice volunteer influenced medical students' comfort with dying and death: a pilot study.

Being comfortable with death and communicating with patients near the end of life are important attributes in palliative care. We developed a hospice volunteer program to teach these attitudes and skills to preclinical medical students. Using a mixed-methods approach, validated surveys measured participants' and non-participants fear of death and communication apprehension regarding dying.

The mechanical effect of the existing cement mantle on the in-cement femoral revision.

Background: Cement-in-cement revision hip arthroplasty is an increasingly popular technique to replace a loose femoral stem which retains much of the original cement mantle. However, some concern exists regarding the retention of the existing fatigued and aged cement in such cement-in-cement revisions. This study investigates whether leaving an existing fatigued and aged cement mantle degrades the mechanical performance of a cement-in-cement revision construct.

Congenital myotonic dystrophy in a national registry.

Aim: To describe the neonatal symptoms, developmental problems and chronic multisystem medical morbidities of congenital myotonic dystrophy (CDM) patients registered in the United States National Registry of Myotonic Dystrophy - a disease-specific, self-report program maintained since 2002. Comparisons with the Canadian Paediatric Surveillance Program for CDM are highlighted.

Methods: Genetically confirmed cases of CDM demonstrating symptoms in the first four weeks of life are described.

In silico prediction of the mechanobiological response of arterial tissue: application to angioplasty and stenting.

One way to restore physiological blood flow to occluded arteries involves the deformation of plaque using an intravascular balloon and preventing elastic recoil using a stent. Angioplasty and stent implantation cause unphysiological loading of the arterial tissue, which may lead to tissue in-growth and reblockage; termed "restenosis." In this paper, a computational methodology for predicting the time-course of restenosis is presented.

Biophysical stimuli induced by passive movements compensate for lack of skeletal muscle during embryonic skeletogenesis.

In genetically modified mice with abnormal skeletal muscle development, bones and joints are differentially affected by the lack of skeletal muscle. We hypothesise that unequal levels of biophysical stimuli in the developing humerus and femur can explain the differential effects on these rudiments when muscle is absent. We find that the expression patterns of four mechanosensitive genes important for endochondral ossification are differentially affected in muscleless limb mutants, with more extreme changes in the expression in the humerus than in the femur.

Bone cell elasticity and morphology changes during the cell cycle.

The mechanical properties of cells are reported to be regulated by a range of factors including interactions with the extracellular environment and other cells, differentiation status, the onset of pathological states, as well as the intracellular factors, for example, the cytoskeleton. The cell cycle is considered to be a well-ordered sequence of biochemical events. A number of processes reported to occur during its progression are inherently mechanical and, as such, require mechanical regulation.

Simulation of fracture healing in the tibia: mechanoregulation of cell activity using a lattice modeling approach.

In this study, a three-dimensional (3D) computational simulation of bone regeneration was performed in a human tibia under realistic muscle loading. The simulation was achieved using a discrete lattice modeling approach combined with a mechanoregulation algorithm to describe the cellular processes involved in the healing process-namely proliferation, migration, apoptosis, and differentiation of cells. The main phases of fracture healing were predicted by the simulation, including the bone resorption phase, and there was a qualitative agreement between the temporal changes in interfragmentary strain and bending stiffness by comparison to experimental data and clinical results.

Inter-species investigation of the mechano-regulation of bone healing: comparison of secondary bone healing in sheep and rat.

Inter-species differences in regeneration exist in various levels. One aspect is the dynamics of bone regeneration and healing, e.g.

Mechanical influences on morphogenesis of the knee joint revealed through morphological, molecular and computational analysis of immobilised embryos.

Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone.

Variability observed in mechano-regulated in vivo tissue differentiation can be explained by variation in cell mechano-sensitivity.

Computational simulations of tissue differentiation have been able to capture the main aspects of tissue formation/regeneration observed in animal experiments-except for the considerable degree of variability reported. Understanding and modelling the source of this variability is crucial if computational tools are to be developed for clinical applications. The objective of this study was to test the hypothesis that differences in cell mechano-sensitivity between individuals can explain the variability of tissue differentiation patterns observed experimentally.

Dynamic patterns of mechanical stimulation co-localise with growth and cell proliferation during morphogenesis in the avian embryonic knee joint.

Muscle contractions begin in early embryonic life, generating forces that regulate the correct formation of the skeleton. In this paper we test the hypothesis that the biophysical stimulation generated by muscle forces may be a causative factor for the changes in shape of the knee joint as it grows. We do this by predicting the spatial and temporal patterns of biophysical stimuli, where cell proliferation and rudiment shape changes occur within the emerging tissues of the joint over time.

Mechanobiology of embryonic skeletal development: Insights from animal models.

A range of clinical conditions in which fetal movement is reduced or prevented can have a severe effect on skeletal development. Animal models have been instrumental to our understanding of the interplay between mechanical forces and skeletal development, particularly the mouse and the chick model systems. In the chick, the most commonly used means of altering the mechanical environment is by pharmaceutical agents which induce paralysis, whereas genetically modified mice with nonfunctional or absent skeletal muscle offer a valuable tool for examining the interplay between muscle forces and skeletogenesis in mammals.

The threshold force required for femoral impaction grafting in revision hip surgery.

Background And Purpose: Femoral impaction grafting requires vigorous impaction to obtain adequate stability without risk of fracture, but the force of impaction has not been determined. We determined this threshold force in a preliminary study using animal femurs.

Methods: Adult sow femurs were used because of their morphological similarity to human femurs in revision hip arthroplasty.

Mechanobiological regulation of the remodelling cycle in trabecular bone and possible biomechanical pathways for osteoporosis.

Background: The rapid loss of trabeculae as observed during osteoporosis is attributed to pathological changes in the bone remodelling process. In this study, it is proposed that osteoporosis is due to altered signals resulting from either (i) a decrease in the mechanosensitivity of the sensor cells or (ii) an increase in the bone tissue elastic modulus.

Methods: To test these hypotheses, a mechanobiological algorithm was developed and applied to simulate the remodelling cycle in a realistic trabecular strut.

Tissue differentiation in an in vivo bioreactor: in silico investigations of scaffold stiffness.

Scaffold design remains a main challenge in tissue engineering due to the large number of requirements that need to be met in order to create functional tissues in vivo. Computer simulations of tissue differentiation within scaffolds could serve as a powerful tool in elucidating the design requirements for scaffolds in tissue engineering. In this study, a lattice-based model of a 3D porous scaffold construct derived from micro CT and a mechano-biological simulation of a bone chamber experiment were combined to investigate the effect of scaffold stiffness on tissue differentiation inside the chamber.