Experimental and numerical characterization of the viscoelastic behaviour of cartilages and soft tissues of the human nose

Dissertação de mestrado integrado em Engenharia BiomédicaThe facial plastic surgery, and particularly the area of rhinoplasty, is undoubtedly a growing up market. Surgical techniques have been evolving to respond to very specific patient desires not only for functional reasons, but also to resolve aesthetic issues. Actually, it is moving plenty of money around the world, being a great scientific and commercial opportunity among researchers. The human nose is composed of three major portions separated by two well-defined regions of transition (K-area and S-area) that are very complicated to deal with in postoperative periods. The viscoelastic behaviour of soft biological tissues, especially that of nasal cartilages and adjacent subcutaneous/fatty tissues, is barely known. There are no studies on the viscoelastic characterization of the mechanical properties of nasal septum (NS), upper lateral cartilages (ULC), and lower lateral cartilages (LLC) in creep and relaxation (basic viscoelasticity features) neither on the determination of frequency- and temperature-dependent properties of these tissues through dynamic mechanical analysis (DMA) in tension and compression. General information on thermal degradations through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) is also missing. Therefore, part of this work intends to fill this lack of the literature giving some insights into the cartilage internal composition and architecture, as well as the specificity of the activated mechanisms under constant stress or strain. Furthermore, numerical simulations were performed based on a hyper-viscoelastic mathematical formulation using a home-made open-source finite element (FE) solver (V-Biomech) in order to find a set of basic constitutive parameters that allow to replicate the experimental creep and relaxation behaviours of nasoseptal cartilage specimens from distinct regions of the quadrilateral cartilage (QLC). Thus, a complete standard biphasic poro-hyper-viscoelastic constitutive law was developed and validated. Finite Element Models (FEM) are gaining relevance to analyse soft biological components. As example, numerical simulations of the viscoelastic behaviours of the specimens harvested from anterior part of the QLC were performed to understand which of the constitutive parameters were more sensitive to achieve the best numerical-experimental agreement. The tools to reproduce these simulations in a more complex geometry (the whole nasal structure, with bony and cartilaginous components) were also developed and presented. The work still goes on it.A cirurgia plástica facial, e em particular a área da rinoplastia, é indubitavelmente um mercado em crescimento. As técnicas cirúrgicas têm evoluído no sentido de dar resposta aos desejos mais específicos de cada paciente não só por razões funcionais, mas também para resolução de problemas estéticos. Atualmente, é uma área que movimenta muito dinheiro em todo o mundo, tornando-se numa evidente oportunidade científica e comercial. O nariz humano está dividido em três regiões principais separadas por duas zonas de transição (áreas K e S) que são muito difíceis de manipular em períodos de recuperação pós-cirurgia. O comportamento viscoelástico de tecidos moles, especialmente o das cartilagens nasais e dos tecidos subcutâneo/adiposo adjacentes, é pouco conhecido. Atualmente, não existem estudos sobre a caracterização de propriedades mecânicas da cartilagem septal nem das cartilagens laterais superiores ou inferiores em fluência e relaxação (características de comportamentos viscoelásticos). A determinação de propriedades mecânicas em função da frequência de oscilação e da temperatura para estes mesmos materiais através de uma análise de DMA em tensão e compressão, assim como informações gerais sobre fenómenos de degradação térmica por DSC e TGA, também não são reportados. Assim sendo, parte desta dissertação pretende preencher esta lacuna da literatura, contribuindo para a compreensão da composição e arquitetura internas da cartilagem e da especificidade dos mecanismos ativados sob influência de uma tensão ou deformação constantes. Além disso, foram levadas a cabo simulações numéricas baseadas numa formulação matemática de híper-viscoelasticidade num software de elementos finitos desenvolvido na Instituição (V-Biomech) e foram encontrados os valores dos parâmetros que permitem replicar o comportamento experimental de fluência e relaxação de cartilagens de diferentes regiões do septo nasal. Assim, uma lei constitutiva que agrega conceitos de híper-elasticidade, viscoelasticidade e permeabilidade, acoplando o distinto comportamento de materiais sólidos e fluidos, foi desenvolvida e validada. Além das simulações do comportamento viscoelástico das amostras colhidas a partir da região anterior do septo, um conjunto de outras ferramentas para aplicação dos mesmos conceitos numa geometria mais complexa foi também desenvolvido e apresentado. Um trabalho que ainda continua

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. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint

Mini-Workshop: Mathematical Methods and Models of Continuum Biomechanics

The workshop Mathematical Methods and Models of Continuum Biomechanics focused on skills and tools providing a rational approach for integrating data that reductionist and molecular approaches in modern biological and medical science has recently provided. The workshop has provided contributions that brought together experts from the (bio-)mechanics and applied mathematics communities in order to highlight the mathematical needs and challenges especially in the fields of soft tissues and DNA mechanics

Computer modelling and simulation of radiofrequency ablation of bone tumors

Radiofrequency ablation (RFA) is a minimally invasive technique used for the treatment of many types of tumors, with a growing interest in the treatment of bone tumors. It uses radio waves to heat up the tissues surrounding a needle-like applicator to destroy the target tumor by exposing the surrounding tissues to high temperatures for a long enough time. However, the technique has been used mostly to treat tumors in other organs, and although it is safe and effective, with little data regarding how much damage it causes in bone tumors, it makes prospective planning challenging. Tumors must be completely destroyed to avoid recurrence but damage to healthy tissues must be minimized. The generation of heat and heat transfer can be modeled mathematically. With this, it was possible to create computer models to simulate the procedure. By looking at retrospective data from patients treated for RFA of bone tumors, the extensions of damage were measured, and the length of the procedure and other parameters were also captured. With these data, it was possible to fit the models to find the optimal parameters to predict the outcomes. Finally, complex 3D computational patient-specific models were created from medical images, and it was possible to replicate the clinical outcomes. This thesis thus showed that computational models could be used to predict the extension of thermal damage, allowing interventional radiologist to plan prospectively with greater accuracy, allowing safer and more effective interventions

A New Genus of Miniaturized and Pug-Nosed Gecko from South America (Sphaerodactylidae: Gekkota)

Sphaerodactyl geckos comprise five genera distributed across Central and South America and the Caribbean. We estimated phylogenetic relationships among sphaerodactyl genera using both separate and combined analyses of seven nuclear genes. Relationships among genera were incongruent at different loci and phylogenies were characterized by short, in some cases zero-length, internal branches and poor phylogenetic support at most nodes. We recovered a polyphyletic Coleodactylus, with Coleodactylus amazonicus being deeply divergent from the remaining Coleodactylus species sampled. The C. amazonicus lineage possessed unique codon deletions in the genes PTPN12 and RBMX while the remaining Coleodactylus species had unique codon deletions in RAG1. Topology tests could not reject a monophyletic Coleodactylus, but we show that short internal branch lengths decreased the accuracy of topology tests because there were not enough data along these short branches to support one phylogenetic hypothesis over another. Morphological data corroborated results of the molecular phylogeny, with Coleodactylus exhibiting substantial morphological heterogeneity. We identified a suite of unique craniofacial features that differentiate C. amazonicus not only from other Coleodactylus species, but also from all other geckos. We describe this novel sphaerodactyl lineage as a new genus, Chatogekko gen. nov. We present a detailed osteology of Chatogekko, characterizing osteological correlates of miniaturization that provide a framework for future studies in sphaerodactyl systematics and biology

Análise Biomecânica de Calo Ósseo usando Método Sem Malha

O osso é um tecido fisiologicamente dinâmico e que quando lesionado tem a capacidade de se reparar com o próprio tecido, não envolvendo um tecido cicatrizante, ao contrário de outros tecidos. Esta característica torna-o particularmente interessante para investigar os processos inerentes de fraturas ósseas. A maior parte das fraturas cicatriza através de uma sequência de processos de diferenciação de tecidos, desde os processos iniciais de hematoma, aos tecidos conjuntivos, e através da cartilagem ao osso. No entanto, qualquer falha neste processo pode resultar em uniões tardias, más uniões ou não uniões. A compreensão na totalidade deste processo ainda constitui um desafio. Os mecanismos que envolvem os processos de estimulação mecânica não se encontram bem compreendidos, em consequência da complexidade dos testes experimentais in vivo, que se tornam dependentes de dados in vitro, tornando difícil validar os pressupostos biológicos. Consequentemente, os modelos computacionais têm demonstrado serem bastante úteis e eficazes na investigação sobre a cicatrização óssea. Desta forma, com o presente trabalho foi possível analisar as condições mecânicas de um calo ósseo resultante de uma fratura, assim como compreender as metodologias de análise numérica aplicadas. O modelo teve por base um estudo in vivo de forma a obter uma variação temporal progressiva da forma do calo e das propriedades mecânicas durante a cicatrização óssea. Com este modelo obtiveram-se os campos de tensão e deformação nas diferentes fases do processo de regeneração, obtendo-se resultados que se encontram em conformidade com a literatura. Adicionalmente, foi aplicado um algoritmo de remodelação óssea em combinação com o Radial Point Interpolation Method (RPIM) que foi capaz de reproduzir as condições apresentadas pela respetiva imagem histológica nesta fase. Por último, espera-se que os trabalhos desenvolvidos neste âmbito possibilitem a conceção de estratégias mais precisas e eficazes tanto para o tratamento como para aceleração da cura. De forma complementar, encontram-se em desenvolvimento modelos específicos dos pacientes e que incorporam variabilidade genética.Bone is a physiologically dynamic tissue that, when injured, has the ability to repair itself, not involving scar tissue, unlike other tissues. This characteristic makes it particularly interesting for investigating the inherent processes of bone fractures. Most fractures heal through a sequence of tissue differentiation processes, from the initial hematoma, to connective tissues and through cartilage to bone. However, any failure in this process can result in a delayed union, mal-union or non-union. A complete understanding of this process is still a challenge. The mechanisms surrounding the mechanical stimulation processes are relatively poorly understood as a result of the complexity of in vivo experimental tests, which become dependent on in vitro data, making it difficult to validate the biological assumptions. Consequently, computational models have proven to be very useful and effective in the investigation of bone healing. Therefore, in the present work, it was possible to analyse the mechanical conditions of a bone callus as a consequence of a fracture and to understand the methodologies of numerical analysis applied. The model was based on an in vivo experimental study in order to obtain a progressive temporal variation of the callus shape and mechanical properties during bone healing. With this model, the stress and strain fields in the different phases of the regeneration process were obtained, where the results are in agreement with the literature. Additionally, a bone remodelling algorithm was applied in combination with the Radial Point Interpolation Method (RPIM), which was able to reproduce the conditions presented by the respective histological image at this stage. Finally, it is expected that the work developed in this area will enable the design of more accurate and effective strategies for both treatment and accelerating healing. Complementarily, patient-specific models and the incorporation of genetic variability are being developed

2D mixed hybrid FEM of lanir model

Osmoelastic media have large negatively charged groups attached to the solid matrix. Due to the fixed charges, the total ion concentration inside the medium is higher than in the surrounding fluid. This excess of ion particles leads to an osmotic pressure difference, which causes swelling of the medium. Lanir's osmoelastic model assumes that small ions are always in equilibrium with the external salt concentration. This means that ion contribution is neglected and the medium is described by two constituents only: the solid and the fluid. In this paper, we implemented Lanir model using MHFEM (Mixed Hybrid Finite Element Method) for consolidation experiment in both 1D and 2D cases, with result verification with analytical solution in 1D. The constituents are assumed to be incompressible. Infinitesimal deformations are assumed. The material is linear elastic, isothermal, isotropic, homogeneous and fully saturated.</p