Le travail présenté dans le manuscrit concerne la conception d'un dispositif médical de classe III pour des applications en ingénierie tissulaire du derme et du disque intervertébral.Il s'agit d'une solution aqueuse de chitosane, stérilisée par autoclave, et dont le pH et l'osmolarité ont été ajustés selon un procédé de dialyse classique. Cette solution possède des propriétés de gélification in situ innovantes, ce qui lui confère de très bonnes propriétés mécaniques quelques minutes après l'injection, sans l'utilisation d'agents de réticulation mais de façon modulable en fonction de la concentration en polymère. De plus, cette solution possède une bonne injectabilité favorisant le développement d'une technique d'implantation mini-invasive pour la régénération du derme et du disque intervertébral. Un critère de performance rhéologique a notamment été mis au point afin de relier l'injectabilité aux propriétés mécaniques de l'injectât (dermal filler).Les propriétés mécaniques de l'injectât gélifié doivent être comparables au tissu natif en particulier pour le dermal filler mais aussi pour le disque intervertébral. Le comportement mécanique viscoélastique du disque intervertébral a été évalué par des essais de relaxation de contraintes et modélisé avec un modèle de Maxwell solide à trois branches. Ces essais ont été conduits sur des disques sains, ayant subi une altération de structure (fenestration) et après l'injection de biopolymères.La solution de chitosane a été injectée (i) dans le tissu cutané de deux modèles animaux : le porc et le rat et (ii) dans le disque intervertébral de deux modèles animaux : le porc et le lapin. La biocompatibilité ainsi que la réponse biologique de solutions/gels physique de chitosane in vivo ont été validées pour tous ces modèles animaux / This work deals with the conception of a class III medical device for applications in tissue engineering of dermis and intervertebral disc.This device consists in an aqueous chitosan solution, sterilized by autoclaving, with pH and osmolality adjusted by a dialysis process. This chitosan solution shows in situ gelation ability with a post-injection increase of mechanical properties. This feature is related to polymer concentration, gelation time, and is performed without external cross-linking agent. In addition, the solution exhibits a good injectability allowing the development of minimally invasive techniques to treat dermis and intervertebral disc diseases. A rheological performance criterion was defined linking injectability to mechanical properties of the implant (dermal filler).Mechanical properties of gel implant formed in contact with body fluids, in situ, have to be similar to that of native tissues. The viscoelastic behavior characterization of intervertebral disc was performed using stress relaxation and was modeled using a generalized solid Maxwell model (composed of three Maxwell elements). The tests were performed on healthy disc, fenestrated discs and after biopolymers injection.Chitosan solutions were injected into (i) porcine and rat cutaneous tissue and (ii) porcine and rabbit intervertebral discs. The biocompatibility and biofunctionality of chitosan solutions and physical hydrogels was evidenced in vivo for all animals

Submitted by Johnny Rodrigues (johnnyrodrigues@ufcg.edu.br) on 2018-04-09T18:16:27Z No. of bitstreams: 1 SANDRO MARTINS DOLGHI - DISSERTAÇÃO PPG-CEMat 2014..pdf: 1349252 bytes, checksum: 7e20e2840dc2a5d2e873cd9b77ed0100 (MD5) / Made available in DSpace on 2018-04-09T18:16:27Z (GMT). No. of bitstreams: 1 SANDRO MARTINS DOLGHI - DISSERTAÇÃO PPG-CEMat 2014..pdf: 1349252 bytes, checksum: 7e20e2840dc2a5d2e873cd9b77ed0100 (MD5) Previous issue date: 2014-12-19 / O culto à beleza está em evidência no Brasil e no mundo, levando ao crescente aumento de técnicas e procedimentos para corrigir defeitos estéticos e minimizar os efeitos do envelhecimento. Diversas substâncias preenchedoras com fluidos de alta viscosidade ou partículas de polímeros em suspensão têm sido utilizadas em larga escala em procedimentos cosméticos e correção de lipodistrofia de pacientes HIV positivos, submetidos à terapia antirretroviral de alta atividade. O uso de polimetilmetacrilato (PMMA) como substância de preenchimento dérmico tem crescido vertiginosamente, assim como o número de reações adversas decorrentes de seu uso. O PMMA vem sendo utilizado, amplamente como matéria prima na fabricação de diversos dispositivos e produtos médicos desde a década de 40, especialmente em função de sua biocompatibilidade, entretanto, ainda há carência de informações e estudos sobre migração e resposta inflamatória das substâncias comercializadas no Brasil para fins de preenchimento dérmico. Este trabalho teve como objetivo avaliar as características físico-químicas de implantes de PMMA comercializados no Brasil para procedimentos de bioplastia, em três apresentações comerciais do produto com diferentes concentrações, visando delimitar limites aceitáveis para fins de registro destes produtos na Agência Nacional de Vigilância Sanitária (Anvisa), com foco na segurança sanitária. As amostras foram caracterizadas por Difração de Raios X (DRX), Espectroscopia na região do infravermelho com transformada de Fourier (FTIR), Microscopia Eletrônica de Varredura (MEV), Espectroscopia por Energia Dispersiva de Raios X (EDS), análise de Calorimetria Exploratória Diferencial (DSC), caracterização por Microscopia Óptica (MO). A técnica de DRX mostrou comportamento semicristalino do PMMA. Com a técnica de FTIR constatou-se os grupos funcionais presentes nos implantes. Por meio das técnicas de MO e MEV foi possível perceber a não homogeneidade em relação ao tamanho das microesferas de PMMA. Pôde-se concluir com os resultados de DSC que o pico endotérmico aumentou de acordo com as variações de concentração do PMMA. A partir dos dados obtidos neste trabalho constata-se que o consumidor está sujeito a riscos, visto que a irregularidade das superfícies e variações nos tamanhos das microesferas pode ocasionar reações adversas, em função da fagocitose das microesferas com tamanho inferior a 20 μm. O crescente uso das técnicas de preenchimento com implantes de PMMA, bem como sua indicação para uso em demais especialidades da medicina, o coloca como material a ser ainda amplamente estudado nas mais diversas aplicações do produto na área médica. / The cult of beauty is in evidence in Brazil and in the world, leading to increasing techniques and procedures to correct aesthetic defects and minimize the effects of aging. Several dermal fillers with high viscosity or polymer particles in suspension fluids have been used in large scale in cosmetic procedures and lipodystrophy correction of HIV-positive patients undergoing HAART activity. The use of polymethylmethacrylate (PMMA) as dermal filler substance has grown dramatically, and the number of adverse reactions arising from its use. PMMA has been used widely as a raw material in manufacturing various medical devices and products since the 40s, especially due to its biocompatibility, however, there is still a lack of information and studies on migration and inflammatory response of substances marketed in Brazil dermal filler purposes. This study aimed to evaluate the physical and chemical characteristics of PMMA implants sold in Brazil for bioplasty procedures in three commercial presentations of the product with different concentrations, in order to delimit acceptable limits for registration of these products at ANVISA, with focus on security health. The samples were characterized by X-ray Diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Spectroscopy Energy Dispersive X-ray (EDS) analysis of Differential Scanning Calorimetry (DSC), characterized by Optical Microscopy (OM). The XRD technique showed semi-crystalline behavior of PMMA. FTIR technique found the functional groups present on the implants. Through OM and SEM techniques we saw the inhomogeneity relative to the size of the PMMA microspheres. One can conclude from the results of the DSC endothermic peak increased in accordance with changes in the concentration of PMMA. From the data obtained in this study it appears that the consumer is subject to risks as uneven surfaces and variations in size of the microspheres can cause adverse reactions, depending on the phagocytosis of microspheres with size less than 20 microns. The increasing use of technical fill with PMMA implants, as well as indications for use in other specialties of medicine, places it as material to be still widely studied in various product applications in the medical field.