O Poli (ácido lático), PLA, e a Policaprolactona, PCL, são dois poliésteres termoplásticos alifáticos, conhecidos por suas capacidades de biodegradabilidade e bioreabsoção e, nos últimos anos, têm sido amplamente estudados como alternativas aos metais em bioimplantes. Por terem características mecânicas distintas, muitas vezes estes materiais são utilizados em blendas poliméricas, visando obter uma combinação construtiva entre tais propriedades; o PLA é mais rígido, tem maior resistência à tração, contudo é frágil; o PCL tem menor rigidez, contudo apresenta maior tenacidade, além de ser extremamente dúctil. A combinação destas propriedades em uma blenda torna a dupla PLA/PCL especialmente atraente à utilização em stents coronarianos, no qual o uso do PLA como único componente do stent pode causar complicações ao paciente, devido à necessidade de aquecimento do material acima de sua temperatura de transição vítrea (ao redor dos 60°C) para que ele possa ser inflado sem risco de uma catastrófica falha. Entretanto, tal aquecimento pode causar necrose dos tecidos coronarianos. Assim sendo, a inclusão do PCL na blenda tem como principal objetivo diminuir a temperatura de transição vítrea do conjunto do PLA. Este estudo teve como principal foco a análise de como o acréscimo de PCL e de dois diferentes tipos de compatibilizantes impactou no comportamento térmico e mecânico das blendas. Para tal, testes dos vinte tipos de blendas desenvolvidas foram submetidos a análises de DSC, DMTA e a ensaios de tração e impacto. Os últimos dois são de fundamental importância, pois o PLA tem pouca ductilidade e resistência ao impacto. Além desses testes, foram efetuadas também análises MEV, com intuito de verificar as modificações morfológicas das blendas ao adicionar-se tanto os compatibilizantes, quanto PCL às formulações. Ensaios espectroscópicos na região do infravermelho também foram conduzidos, a fim de analisar-se, além das estruturas químicas dos componentes da blenda, as interações entre eles e as modificações espectrais causadas por ela. Testes preliminares, como o GPC e a termogravimetria, também estão presentes. Com isso foi possível, além de fazer a determinação da massa molar dos componentes da blenda, ter acesso a dados acerca da degradação térmica dos polímeros utilizados. Ademais, a fim de analisar-se preliminarmente o potencial das blendas desenvolvidas como biomaterial, foram efetuados testes de Citotoxidade em formulações selecionadas. Como resultado da intensa investigação sobre as propriedades das blendas PLA/PCL, compatibilizadas ou não, foi verificado grande aumento de ductilidade nas formulações, sem perda apreciável de resistência mecânica. Em muitas das blendas, houve também expressivo aumento na tenacidade. Em contrapartida, não foram verificadas alterações significativas no perfil térmico das amostras, conforme DMTA e DSC. / The Polylactide, PLA, and the Polycaprolactone, PCL, are two thermoplastic aliphatic polyesters, known for their biodegradability and bioresorption abilities and, in the latest years, they have been extensively studied as alternatives to metals in bioimplants. Since they have distinct mechanical properties, these materials are many times used in polymeric blends, in order to obtain a constructive combination of the mechanical properties; the Polylactide is more rigid and has better tensile resistance, however it is brittle; on the other hand, the Polycaprolactone has lower rigidity, but it has better toughness, in addition to its great ductility. The combination of these properties in a blend makes the PLA/PCL configuration especially attractive to the use in coronary stents, on which the use of the PLA as only component may cause serious complications to the patient, due to its need to be warmed above its glass transition temperature (around 60°C) in order to be inflated without the risk of any catastrophic failure. However, this heating might cause necrosis of the coronary tissue. The inclusion of the PCL on the blend has, as a main goal, the objective of, in addition to lowering the glass transition temperature on the aggregate, is to allow the expansion of the material with no risk of failure. This study focused on how the addition of PCL and two different kinds of compatibilizers alters the thermal and mechanical behavior of the blends. To do so, tests were performed on the twenty types of blends developed, e.g. DSC, DMTA, tensile and impact tests. The latter two are of critical importance, because the Polylactide has little toughness and ductility. Furthermore, SEM was also performed in order to verify the morphological changes caused by increasing the PCL concentration on the blends, as well as the addition of the compatibilizers. Infrared spectroscopic analysis was also conducted on the blends, thus the chemical structures of the main components of the blends could be assessed, as well as the interactions and the spectral changes caused by it. Preliminary tests, for example, GPC and thermogravimetry were also conducted. With this data, it was possible to determine the molar mass of the blends components and assess the thermal degradation profile of the materials used. Moreover, preliminary tests were conducted in order to determine the potential some selected blends have as biomaterials. As the result of this deep research on the PLA/PCL blends properties, compatibilized or not, it was possible to achieve relevant increase in the ductility and toughness of the formulations, with no significant loss in terms of mechanical resistance. On the other hand, no significant changes on the thermal profile of the blends were observed, according to DMTA and DSC tests.

O Poli (ácido lático), PLA, e a Policaprolactona, PCL, são dois poliésteres termoplásticos alifáticos, conhecidos por suas capacidades de biodegradabilidade e bioreabsoção e, nos últimos anos, têm sido amplamente estudados como alternativas aos metais em bioimplantes. Por terem características mecânicas distintas, muitas vezes estes materiais são utilizados em blendas poliméricas, visando obter uma combinação construtiva entre tais propriedades; o PLA é mais rígido, tem maior resistência à tração, contudo é frágil; o PCL tem menor rigidez, contudo apresenta maior tenacidade, além de ser extremamente dúctil. A combinação destas propriedades em uma blenda torna a dupla PLA/PCL especialmente atraente à utilização em stents coronarianos, no qual o uso do PLA como único componente do stent pode causar complicações ao paciente, devido à necessidade de aquecimento do material acima de sua temperatura de transição vítrea (ao redor dos 60°C) para que ele possa ser inflado sem risco de uma catastrófica falha. Entretanto, tal aquecimento pode causar necrose dos tecidos coronarianos. Assim sendo, a inclusão do PCL na blenda tem como principal objetivo diminuir a temperatura de transição vítrea do conjunto do PLA. Este estudo teve como principal foco a análise de como o acréscimo de PCL e de dois diferentes tipos de compatibilizantes impactou no comportamento térmico e mecânico das blendas. Para tal, testes dos vinte tipos de blendas desenvolvidas foram submetidos a análises de DSC, DMTA e a ensaios de tração e impacto. Os últimos dois são de fundamental importância, pois o PLA tem pouca ductilidade e resistência ao impacto. Além desses testes, foram efetuadas também análises MEV, com intuito de verificar as modificações morfológicas das blendas ao adicionar-se tanto os compatibilizantes, quanto PCL às formulações. Ensaios espectroscópicos na região do infravermelho também foram conduzidos, a fim de analisar-se, além das estruturas químicas dos componentes da blenda, as interações entre eles e as modificações espectrais causadas por ela. Testes preliminares, como o GPC e a termogravimetria, também estão presentes. Com isso foi possível, além de fazer a determinação da massa molar dos componentes da blenda, ter acesso a dados acerca da degradação térmica dos polímeros utilizados. Ademais, a fim de analisar-se preliminarmente o potencial das blendas desenvolvidas como biomaterial, foram efetuados testes de Citotoxidade em formulações selecionadas. Como resultado da intensa investigação sobre as propriedades das blendas PLA/PCL, compatibilizadas ou não, foi verificado grande aumento de ductilidade nas formulações, sem perda apreciável de resistência mecânica. Em muitas das blendas, houve também expressivo aumento na tenacidade. Em contrapartida, não foram verificadas alterações significativas no perfil térmico das amostras, conforme DMTA e DSC. / The Polylactide, PLA, and the Polycaprolactone, PCL, are two thermoplastic aliphatic polyesters, known for their biodegradability and bioresorption abilities and, in the latest years, they have been extensively studied as alternatives to metals in bioimplants. Since they have distinct mechanical properties, these materials are many times used in polymeric blends, in order to obtain a constructive combination of the mechanical properties; the Polylactide is more rigid and has better tensile resistance, however it is brittle; on the other hand, the Polycaprolactone has lower rigidity, but it has better toughness, in addition to its great ductility. The combination of these properties in a blend makes the PLA/PCL configuration especially attractive to the use in coronary stents, on which the use of the PLA as only component may cause serious complications to the patient, due to its need to be warmed above its glass transition temperature (around 60°C) in order to be inflated without the risk of any catastrophic failure. However, this heating might cause necrosis of the coronary tissue. The inclusion of the PCL on the blend has, as a main goal, the objective of, in addition to lowering the glass transition temperature on the aggregate, is to allow the expansion of the material with no risk of failure. This study focused on how the addition of PCL and two different kinds of compatibilizers alters the thermal and mechanical behavior of the blends. To do so, tests were performed on the twenty types of blends developed, e.g. DSC, DMTA, tensile and impact tests. The latter two are of critical importance, because the Polylactide has little toughness and ductility. Furthermore, SEM was also performed in order to verify the morphological changes caused by increasing the PCL concentration on the blends, as well as the addition of the compatibilizers. Infrared spectroscopic analysis was also conducted on the blends, thus the chemical structures of the main components of the blends could be assessed, as well as the interactions and the spectral changes caused by it. Preliminary tests, for example, GPC and thermogravimetry were also conducted. With this data, it was possible to determine the molar mass of the blends components and assess the thermal degradation profile of the materials used. Moreover, preliminary tests were conducted in order to determine the potential some selected blends have as biomaterials. As the result of this deep research on the PLA/PCL blends properties, compatibilized or not, it was possible to achieve relevant increase in the ductility and toughness of the formulations, with no significant loss in terms of mechanical resistance. On the other hand, no significant changes on the thermal profile of the blends were observed, according to DMTA and DSC tests.

The study of internal structure of materials has always been an essential issue in a variety of application fields, from the medical radiology to the materials science. X-ray computed microtomography (with both conventional and synchrotron radiation sources) has a great potential for these purposes because its three-dimensional and non destructive nature as well as the fact that it does not require any sample preparation and it allows to study samples under stress or after consecutive treatments. The recent developments of new X-ray sources with innovative imaging techniques, as well as novel high resolution detectors, allow moving forward the maximum achievable resolution of this technique to a few micrometers or even less. This contributed to increase its application in biomedical purposes, but also to raise the need for quantitative analysis of the reconstructed data. Indeed in most of the cases a quantitative characterization of the samples microstructures is needed to better understand their physical and chemical behavior, the effects of manufacturing process or the response to stress. Dedicated software packages have been developed to perform a geometrical and morphological characterization of the samples texture and to evaluate some typical parameters commonly used to classify porous media such as porosity, cell size distribution, connectivity and anisotropy. In this work two case studies have been considered for the application of a quantitative analysis approach to microtomography datasets: the first concerns the characterization of bone ingrowth within tissue engineering scaffolds, while the second is related to the extraction of morphological descriptors for the architecture of human skull bones. It will be shown how suitable image processing and analysis techniques are able to effectively quantify significant parameters such as the trabecular thickness of the skull bones as well as the porosity and the degree of connectivity of bone tissue engineering scaffolds. Similar quantitative analysis methods applied to microtomography images have to be considered as an effective methodology for a comprehensive characterization of other biomedical samples.

Cette thèse transdisciplinaire réalisée en collaboration avec le laboratoire SPCTS (Sciences des Procédés Céramiques et Traitement de Surface) et l’EA 3842 (Homéostasie cellulaire et pathologies) de l’université de Limoges est un projet de recherche à l’interface entre la biologie et la chimie et a été consacrée à l’étude de l’influence des propriétés physico-chimiques de biocéramiques de phosphate de calcium sur leur comportement biologique in vitro.L’exploration des processus d’interaction entre matériaux et cellules reste une problématique scientifique de premier plan tant d’un point de vue fondamental qu’appliqué pour la mise au point de biomatériaux performants. L’objectif final est d’optimiser l’efficacité thérapeutique des céramiques phosphocalciques comme matériaux de substitution pour la régénération osseuse. La première partie de la thèse est une revue bibliographique générale présentant la problématique actuelle abordée en lien avec les besoins cliniques et les limitations des études actuelles. Les connaissances sur la biologie du tissu osseux sain ainsi que les aspects de régulation du processus de remodelage osseux ont également été abordés dans ce chapitre. Ce chapitre se termine par une synthèse bibliographique sur les biomatériaux et la régénération osseuse. Le chapitre 2 est relatif à la synthèse puis à la caractérisation physico-chimique des matériaux céramiques. Des céramiques de trois compositions chimiques : HA (hydroxyapatite : Ca10(PO4)6(OH)2 , SiHA (hydroxyapatite silicatée : Ca10(PO4)5,6(SiO4)0,42(OH)1,6 et CHA (hydroxyapatite carbonatée : Ca9,5(PO4)5,5(CO3)0,48(OH)1,08(CO3)0,23 , chacune avec deux microstructures différentes : dense ou poreuse, ont été élaborées et rigoureusement caractérisées (porosité, topographie de surface, mouillabilité, potentiel zêta, taille des grains, distribution et taille des pores, surface spécifique). Le chapitre 3 décrit l’approche expérimentale employée pour l’évaluation biologique des interactions matériaux/cellules explorées dans ce travail. Les analyses biologiques ont été réalisées avec deux lignées cellulaires différentes. La lignée cellulaire pré-ostéoblastique MC3T3-E1 et la lignée cellulaire de monocytes/macrophages, précurseurs des ostéoclastes RAW 264.7, (très importantes pour les aspects osseux, mais moins souvent explorées que les lignées ostéoblastiques dans la littérature). Enfin, le chapitre 4 reporte et commente les résultats biologiques obtenus dans ce travail. Tous les biomatériaux évalués dans cette étude sont biocompatibles, néanmoins, le biomatériau poreux CHA s’est avéré le plus prometteur des six variantes de biomatériaux testés. / This transdisciplinary thesis, carried out in collaboration with the SPCTS laboratory (sciences of ceramic processes and surface treatment) and EA 3842 (Cellular homoeostasis and pathologies) of the University of Limoges, is a research project at the interface between biology and chemistry and was devoted to the study of the influence of the physico-chemical properties of calcium phosphate bioceramics on their biological behavior in vitro.The exploration of the processes of interaction between materials and cells remains a major scientific issue, both from a fundamental and applied point of view for the development of highperformance biomaterials. The ultimate objective is to optimize the therapeutic efficiency of phosphocalcic ceramics as substitute materials for bone regeneration.The first part of the thesis is a general bibliographic review presenting the current issues tackled with the clinical needs and limitations of current studies. Knowledge of the biology of healthy bone tissue as well as the regulatory aspects of the bone remodeling process was also discussed in this chapter. It includes also a bibliographic overview of biomaterials and bone regeneration.Chapter 2 relates to the synthesis and the physico-chemical characterization of ceramic materials. HA (hydroxyapatite: Ca10 (PO4) 6 (OH) 2, SiHA (silicated hydroxyapatite: Ca10 (PO4) 5.6 (SiO4) 0.42 (OH) 1.6 and CHA (carbonated hydroxyapatite: Ca9.5 (PO4) 5.5 (CO3) 0.48 (OH) 1.08 (CO3) 0.23, ceramics each with two different microstructures : dense or porous, have been elaborated and thoroughly characterized (porosity, surface topography, wettability, zeta potential, grain size, pore size and distribution, specific surface area). Chapter 3 describes the experimental approach used for the biological evaluation of the interactions between materials and cells. Biological analyzes were performed with two different cell lines. The pre-osteoblastic MC3T3-E1 cell line and the RAW 264.7cell line of monocytes / macrophages, precursors of the steoclasts, (very important for the bone aspects, but less often explored than the osteoblastic lines in the literature). Finally, Chapter 4 reports and comments on the biological results obtained in this work. All biomaterials evaluated are biocompatible, nevertheless, the porous CHA biomaterial was the most promising of the six variants of biomaterials tested.