Damage and fracture of biological and biomedical materials

In the last decade, the topic of damage and fracture of biological and biomedical materials not only became one of the central research areas in the healthcare engineering, but also drew attention of specialists in mechanics of materials and fracture. One of the motivations behind these developments is a continuing increase in the use of medical devices made of various materials that are exposed to challenging loading and environmental conditions. Many of them should have significant levels of durability to avoid recurring surgical interventions (typical examples being implants for hip and knee replacements or dental implants). A lack of understanding of their responses to specific conditions and interaction with biological environment can result in malfunctioning and failures or traumas to surrounding tissues. The typical application problems are additionally complicated by insufficient knowledge of mechanical behaviour of biomaterials at various length and time scales and under different loading conditions including their fracture and fatigue. These types of application presuppose the understanding of properties and performance of two classes of materials – natural (biomaterials) and engineering (biomedical materials), as well as their interaction at interfaces between, on the one hand, life tissues (or organs) and, on the other hand, implants and prostheses. Among engineering materials, used in such applications, are familiar metals and alloys, ceramics, polymers and composites. Their properties and performance seem to be well studied; still, biomedical applications are characterised by rather specific usability envelopes as well as, in most cases, additional constraints such as non-toxicity (biocompatibility) and/or resistance to harsh physiological environments. In some cases, a requirement, opposite to structural integrity, is needed, e.g. controlled degradation for scaffolds and stents..

Modelling actin polymerization: the effect on confined cell migration

The aim of this work is to model cell motility under conditions of mechanical confinement. This cell migration mode may occur in extravasation of tumour and neutrophil-like cells. Cell migration is the result of the complex action of different forces exerted by the interplay between myosin contractility forces and actin processes. Here, we propose and implement a finite element model of the confined migration of a single cell. In this model, we consider the effects of actin and myosin in cell motility. Both filament and globular actin are modelled. We model the cell considering cytoplasm and nucleus with different mechanical properties. The migration speed in the simulation is around 0.1 µm/min, which is in agreement with existing literature. From our simulation, we observe that the nucleus size has an important role in cell migration inside the channel. In the simulation the cell moves further when the nucleus is smaller. However, this speed is less sensitive to nucleus stiffness. The results show that the cell displacement is lower when the nucleus is stiffer. The degree of adhesion between the channel walls and the cell is also very important in confined migration. We observe an increment of cell velocity when the friction coefficient is higher

A multi-scale modelling framework combining musculoskeletal rigid-body simulations with adaptive finite element analyses, to evaluate the impact of femoral geometry on hip joint contact forces and femoral bone growth

Multi-scale simulations, combining muscle and joint contact force (JCF) from musculoskeletal simulations with adaptive mechanobiological finite element analysis, allow to estimate musculoskeletal loading and predict femoral growth in children. Generic linearly scaled musculoskeletal models are commonly used. This approach, however, neglects subject- and age-specific musculoskeletal geometry, e.g. femoral neck-shaft angle (NSA) and anteversion angle (AVA). This study aimed to evaluate the impact of proximal femoral geometry, i.e. altered NSA and AVA, on hip JCF and femoral growth simulations. Musculoskeletal models with NSA ranging from 120° to 150° and AVA ranging from 20° to 50° were created and used to calculate muscle and hip JCF based on the gait analysis data of a typically developing child. A finite element model of a paediatric femur was created from magnetic resonance images. The finite element model was morphed to the geometries of the different musculoskeletal models and used for mechanobiological finite element analysis to predict femoral growth trends. Our findings showed that hip JCF increase with increasing NSA and AVA. Furthermore, the orientation of the hip JCF followed the orientation of the femoral neck axis. Consequently, the osteogenic index, which is a function of cartilage stresses and defines the growth rate, barely changed with altered NSA and AVA. Nevertheless, growth predictions were sensitive to the femoral geometry due to changes in the predicted growth directions. Altered NSA had a bigger impact on the growth results than altered AVA. Growth simulations based on mechanobiological principles were in agreement with reported changes in paediatric populations

Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas

Accelerometer Measured Levels of Moderate-to-Vigorous Intensity Physical Activity and Sedentary Time in Children and Adolescents with Chronic Disease: a Systematic Review and Meta-Analysis

Context: Moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) are important for child and adolescent health. Objective: To examine habitual levels of accelerometer measured MVPA and ST in children and adolescents with chronic disease, and how these levels compare with healthy peers. Methods: Data sources: An extensive search was carried out in Medline, Cochrane library, EMBASE, SPORTDiscus and CINAHL from 2000–2017. Study selection: Studies with accelerometer-measured MVPA and/or ST (at least 3 days and 6 hours/day to provide estimates of habitual levels) in children 0–19 years of age with chronic diseases but without co-morbidities that would present major impediments to physical activity. In all cases patients were studied while well and clinically stable. Results: Out of 1592 records, 25 studies were eligible, in four chronic disease categories: cardiovascular disease (7 studies), respiratory disease (7 studies), diabetes (8 studies), and malignancy (3 studies). Patient MVPA was generally below the recommended 60 min/day and ST generally high regardless of the disease condition. Comparison with healthy controls suggested no marked differences in MVPA between controls and patients with cardiovascular disease (1 study, n = 42) and type 1 diabetes (5 studies, n = 400; SMD -0.70, 95% CI -1.89 to 0.48, p = 0.25). In patients with respiratory disease, MVPA was lower in patients than controls (4 studies, n = 470; SMD -0.39, 95% CI -0.80, 0.02, p = 0.06). Meta-analysis indicated significantly lower MVPA in patients with malignancies than in the controls (2 studies, n = 90; SMD -2.2, 95% CI -4.08 to -0.26, p = 0.03). Time spent sedentary was significantly higher in patients in 4/10 studies compared with healthy control groups, significantly lower in 1 study, while 5 studies showed no significant group difference. Conclusions: MVPA in children/adolescents with chronic disease appear to be well below guideline recommendations, although comparable with activity levels of their healthy peers except for children with malignancies. Tailored and disease appropriate intervention strategies may be needed to increase MVPA and reduce ST in children and adolescents with chronic disease

Seguimiento de las guías españolas para el manejo del asma por el médico de atención primaria: un estudio observacional ambispectivo

Objetivo Evaluar el grado de seguimiento de las recomendaciones de las versiones de la Guía española para el manejo del asma (GEMA 2009 y 2015) y su repercusión en el control de la enfermedad. Material y métodos Estudio observacional y ambispectivo realizado entre septiembre del 2015 y abril del 2016, en el que participaron 314 médicos de atención primaria y 2.864 pacientes. Resultados Utilizando datos retrospectivos, 81 de los 314 médicos (25, 8% [IC del 95%, 21, 3 a 30, 9]) comunicaron seguir las recomendaciones de la GEMA 2009. Al inicio del estudio, 88 de los 314 médicos (28, 0% [IC del 95%, 23, 4 a 33, 2]) seguían las recomendaciones de la GEMA 2015. El tener un asma mal controlada (OR 0, 19, IC del 95%, 0, 13 a 0, 28) y presentar un asma persistente grave al inicio del estudio (OR 0, 20, IC del 95%, 0, 12 a 0, 34) se asociaron negativamente con tener un asma bien controlada al final del seguimiento. Por el contrario, el seguimiento de las recomendaciones de la GEMA 2015 se asoció de manera positiva con una mayor posibilidad de que el paciente tuviera un asma bien controlada al final del periodo de seguimiento (OR 1, 70, IC del 95%, 1, 40 a 2, 06). Conclusiones El escaso seguimiento de las guías clínicas para el manejo del asma constituye un problema común entre los médicos de atención primaria. Un seguimiento de estas guías se asocia con un control mejor del asma. Existe la necesidad de actuaciones que puedan mejorar el seguimiento por parte de los médicos de atención primaria de las guías para el manejo del asma. Objective: To assess the degree of compliance with the recommendations of the 2009 and 2015 versions of the Spanish guidelines for managing asthma (Guía Española para el Manejo del Asma [GEMA]) and the effect of this compliance on controlling the disease. Material and methods: We conducted an observational ambispective study between September 2015 and April 2016 in which 314 primary care physicians and 2864 patients participated. Results: Using retrospective data, we found that 81 of the 314 physicians (25.8%; 95% CI 21.3–30.9) stated that they complied with the GEMA2009 recommendations. At the start of the study, 88 of the 314 physicians (28.0%; 95% CI 23.4–33.2) complied with the GEMA2015 recommendations. Poorly controlled asthma (OR, 0.19; 95% CI 0.13–0.28) and persistent severe asthma at the start of the study (OR, 0.20; 95% CI 0.12–0.34) were negatively associated with having well-controlled asthma by the end of the follow-up. In contrast, compliance with the GEMA2015 recommendations was positively associated with a greater likelihood that the patient would have well-controlled asthma by the end of the follow-up (OR, 1.70; 95% CI 1.40–2.06). Conclusions: Low compliance with the clinical guidelines for managing asthma is a common problem among primary care physicians. Compliance with these guidelines is associated with better asthma control. Actions need to be taken to improve primary care physician compliance with the asthma management guidelines

Subject-specific musculoskeletal loading of the tibia: Computational load estimation

Item does not contain fulltextThe systematic development of subject-specific computer models for the analysis of personalized treatments is currently a reality. In fact, many advances have recently been developed for creating virtual finite element-based models. These models accurately recreate subject-specific geometries and material properties from recent techniques based on quantitative image analysis. However, to determine the subject-specific forces, we need a full gait analysis, typically in combination with an inverse dynamics simulation study. In this work, we aim to determine the subject-specific forces from the computer tomography images used to evaluate bone density. In fact, we propose a methodology that combines these images with bone remodelling simulations and artificial neural networks. To test the capability of this novel technique, we quantify the personalized forces for five subject-specific tibias using our technique and a gait analysis. We compare both results, finding that similar vertical loads are estimated by both methods and that the dominant part of the load can be reliably computed. Therefore, we can conclude that the numerical-based technique proposed in this work has great potential for estimating the main forces that define the mechanical behaviour of subject-specific bone

Model based design of self-healing expandable coatings under different environmental conditions

A long-lasting barrier protection at damaged sites of coated system can be achieved by means of an active response of the primer. This may be attained through the release of reactive liquids from dispersed containers, the increase of the local mobility of the polymeric network, or the expansion of (dispersed elements in) the primer [1]. Such self-healing mechanisms provide an excellent strategy towards repeated and sustained self-repair properties and, additionally, are not incompatible with the inclusion of passive elements within the primer to produce a corrosion inhibition response. This work focuses on the modelling and simulation of expandable coatings resembling systems that contain thin clay-based interlayers [2]. However, a similar methodology could be applied to treat the hydraulic growth of inorganic grains in PPS coatings [3]. The expansion of a theoretical porous plastic primer is triggered by the ingress of environmental moisture. The volumetric growth of the primer into the crack is investigated under different humidity, temperature and atmospheric pressure conditions resembling different geographical locations (coastline vs. inland, changes in altitude and latitude, etc). Furthermore, the reversibility of the expansion process is investigated through hysteresis cycles resembling the change of the environmental conditions over a time lapse of several hours up to days. The self-sealing capacity of the coating is estimated from the maximum crack width that can be filled. A full characterization of self-sealing efficiency is given in terms of key design parameters such as porosity, permeability, sorption behaviour, swelling range, shear modulus, layers widths and adhesion properties.Aerospace Structures & MaterialsAerospace Engineerin

A theoretical analysis of the scale separation in a model to predict solid tumour growth

Solid tumour growth depends on a host of factors which affect the cell life cycle and extracellular matrix vascularization that leads to a favourable environment. The whole solid tumour can either grow or wither in response to the action of the immune system and therapeutics. A personalised mathematical model of such behaviour must consider both the intra- and inter-cellular dynamics and the mechanics of the solid tumour and its microenvironment. However, such wide range of spatial and temporal scales can hardly be modelled in a single model, and require the so-called multiscale models, defined as orchestrations of single-scale component models, connected by relation models that transform the data for one scale to another. While multiscale models are becoming common, there is a well-established engineering approach to the definition of the scale separation, e.g., how the spatiotemporal continuum is split in the various component models. In most studies scale separation is defined as natural, linked to anatomical concepts such as organ, tissue, or cell; but these do not provide reliable definition of scales: for examples skeletal organs can be as large as 500 mm (femur), or as small as 3 mm (stapes). Here we apply a recently proposed scale-separation approach based on the actual experimental and computational limitations to a patient-specific model of the growth of neuroblastoma. The resulting multiscale model can be properly informed with the available experimental data and solved in a reasonable timeframe with the available computational resources

A mechanical model for the self healing response of coatings based on expansive phases (abstract)

Aerospace Structures & MaterialsAerospace Engineerin