Efeitos da exposição de produtos de desgaste de implantes de titânio a células do tecido ósseo
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2018-04-20
Autores
Costa, Bruna Carolina
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Universidade Estadual Paulista (Unesp)
Resumo
Dentre os biomateriais metálicos, largamente empregados pela indústria biomédica, o titânio (Ti) e suas ligas, principalmente o sistema Ti-6Al-4V (responsável por 45% da produção total de titânio como biomaterial) representam a principal escolha para a confecção de implantes ortopédicos e dentários. No entanto, processos de degradação (corrosão, desgaste e tribocorrosão) atuantes sobre estas ligas podem ocasionar a liberação de partículas e íons metálicos (comumente referidos produtos de desgaste ou debris), o que pode representar uma situação perigosa in vivo. Neste contexto, as propriedades físico-químicas dos produtos de desgaste irão influenciar fortemente o tipo e intensidade das respostas de um organismo vivo após sua exposição aos mesmos. De forma geral, a interação de tais produtos com as células dos tecidos adjacentes ao implante e do sistema imune pode desencadear processos de sinalização, nomeadamente em termos da produção e liberação de citocinas pró-inflamatórias, conduzindo a osteólise (reabsorção óssea) e consequente falha do implante. Ademais, muitas preocupações têm sido levantadas com relação à liberação de partículas e íons compostos pelos elementos alumínio e vanádio. Alternativamente, novas ligas de titânio isentas da adição destes elementos têm sido propostas nos últimos anos, dentre as quais podemos citar, por exemplo, a liga Ti-15Zr-15Mo. Neste trabalho, foram avaliados (in vitro), a partir de um modelo de células de camundongo, os possíveis efeitos relacionados à exposição de íons vanádio às células dos tecidos ósseo e conjuntivo (fibroblastos e osteoblastos). Ademais, a especiação iônica para determinação dos íons vanádio predominantemente relacionados aos resultados obtidos também foi realizada. Complementarmente, a avaliação do comportamento com relação à tribocorrosão para duas ligas de titânio (Ti-6Al-4V e Ti-15Zr-15Mo), a produção e caracterização de partículas de desgaste a partir destas ligas e avaliação dos efeitos relacionados à exposição de tais partículas às células do tecido ósseo (osteoblastos) humano, nomeadamente em termos de viabilidade celular e produção de citocinas pró-inflamatórias, também foram propostas. De acordo com os resultados obtidos, foi possível verificar que as espécies iônicas de vanádio predominantemente dissolvidas nos meios de cultura utilizados para os experimentos in vitro com os osteoblastos e fibroblastos de camundongo foram essencialmente vanadatos, nomeadamente H2VO4- e HVO42-. Verificou-se também que a interação destas espécies iônicas com as células das linhagens celulares testadas, principalmente fibroblastos, pode causar uma diminuição significativa em viabilidade para concentrações próximas aquela possível ser encontrada in vivo em pacientes que apresentam mau funcionamento de seu dispositivo médico baseado na liga Ti-6Al-4V. Para as partículas de desgaste geradas a partir de ensaios de tribocorrosão sobre as ligas Ti-6Al-4V e Ti-15Zr-15Mo foram verificadas características semelhantes com relação à morfologia e a capacidade de preservar a composição e estrutura cristalina do material a partir do qual são geradas. No entanto, diferenças significativas em termos de tamanho foram observadas. Por fim, verificou-se também que a interação das partículas de desgaste obtidas (ambas as composições) com células do tecido ósseo humano, in vitro, pode provocar a diminuição da viabilidade ou (possivelmente) alterações no metabolismo celular, além de conduzir a um aumento na produção das citocinas pró-inflamatórias interleucina-6 e prostaglandina E2.
Among the metallic biomaterials, widely used in the biomedical industry, titanium (Ti) and its alloys, mainly the Ti-6Al-4V system (responsible for 45% of the total titanium production as biomaterial) represent the main choice for orthopedic and dental implants’ manufacturing. However, degradation processes (corrosion, wear and tribocorrosion) acting on these alloys may lead the release of metallic particles and/or ions (also referred as wear products or debris), and this may represent a dangerous situation in vivo. In this context, the wear products’ physical-chemical properties will strongly influence the type and intensity of the living organism responses after their exposure to them. In general, these products’ interaction with the implants’ surrounding tissues and immune system cells may trigger signaling processes, particularly in terms of the proinflammatory cytokines production and release, leading to osteolysis (bone resorption) and consequent implant loosening. Additionally, many concerns have been raised regarding the release of particles and ions composed by aluminum and vanadium. Alternatively, new vanadium and aluminum-free titanium alloys have been proposed in recent years, among which it is possible to mention, for example, the Ti-15Zr-15Mo alloy. In this work, the possible effects related to the vanadium ions exposure to bone and connective tissue cells (fibroblasts and osteoblasts) were evaluated (in vitro), from a mouse cells’ model. Also, ionic speciation analyzes were also performed in order to determine the vanadium ions related to the obtained results. Complementarily, the tribocorrosion behavior evaluation of two titanium alloys (Ti-6Al-4V and Ti-15Zr-15Mo), the production and characterization of wear particles generated from these alloys and the evaluation of the possible effects related to these particles exposure to human osteoblasts (particularly in terms of cell viability and proinflammatory cytokines production) were also proposed. According to the obtained results, it was possible to verify that the vanadium ionic species predominantly dissolved in the culture media used for the in vitro experiments with mouse osteoblasts and fibroblasts were essentially vanadates, namely H2VO4- and HVO42-. It has also been found that the interaction of such ionic species with the tested cells lines, mainly fibroblasts, may lead to a significant decrease in cell viability at concentrations close to that possible to be found in vivo for patients who present malfunctioning of their medical device based on Ti-6Al-4V alloy. Regarding the wear particles generated from tribocorrosion assays on Ti-6Al-4V and Ti-15Zr-15Mo alloys, similar characteristics were verified, mainly in morphology and the ability to preserve the chemical composition and crystal structure of the material from which are generated. However, significant differences in size were observed. Finally, it has also been found that the interaction of the obtained wear particles (both compositions) with human bone tissue cells, in vitro, may be related to decreased viability or (possibly) changes in cellular metabolism, in addition to leading to an increased production of the interleukin-6 and prostaglandin E2 proinflammatory cytokines
Among the metallic biomaterials, widely used in the biomedical industry, titanium (Ti) and its alloys, mainly the Ti-6Al-4V system (responsible for 45% of the total titanium production as biomaterial) represent the main choice for orthopedic and dental implants’ manufacturing. However, degradation processes (corrosion, wear and tribocorrosion) acting on these alloys may lead the release of metallic particles and/or ions (also referred as wear products or debris), and this may represent a dangerous situation in vivo. In this context, the wear products’ physical-chemical properties will strongly influence the type and intensity of the living organism responses after their exposure to them. In general, these products’ interaction with the implants’ surrounding tissues and immune system cells may trigger signaling processes, particularly in terms of the proinflammatory cytokines production and release, leading to osteolysis (bone resorption) and consequent implant loosening. Additionally, many concerns have been raised regarding the release of particles and ions composed by aluminum and vanadium. Alternatively, new vanadium and aluminum-free titanium alloys have been proposed in recent years, among which it is possible to mention, for example, the Ti-15Zr-15Mo alloy. In this work, the possible effects related to the vanadium ions exposure to bone and connective tissue cells (fibroblasts and osteoblasts) were evaluated (in vitro), from a mouse cells’ model. Also, ionic speciation analyzes were also performed in order to determine the vanadium ions related to the obtained results. Complementarily, the tribocorrosion behavior evaluation of two titanium alloys (Ti-6Al-4V and Ti-15Zr-15Mo), the production and characterization of wear particles generated from these alloys and the evaluation of the possible effects related to these particles exposure to human osteoblasts (particularly in terms of cell viability and proinflammatory cytokines production) were also proposed. According to the obtained results, it was possible to verify that the vanadium ionic species predominantly dissolved in the culture media used for the in vitro experiments with mouse osteoblasts and fibroblasts were essentially vanadates, namely H2VO4- and HVO42-. It has also been found that the interaction of such ionic species with the tested cells lines, mainly fibroblasts, may lead to a significant decrease in cell viability at concentrations close to that possible to be found in vivo for patients who present malfunctioning of their medical device based on Ti-6Al-4V alloy. Regarding the wear particles generated from tribocorrosion assays on Ti-6Al-4V and Ti-15Zr-15Mo alloys, similar characteristics were verified, mainly in morphology and the ability to preserve the chemical composition and crystal structure of the material from which are generated. However, significant differences in size were observed. Finally, it has also been found that the interaction of the obtained wear particles (both compositions) with human bone tissue cells, in vitro, may be related to decreased viability or (possibly) changes in cellular metabolism, in addition to leading to an increased production of the interleukin-6 and prostaglandin E2 proinflammatory cytokines
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Palavras-chave
Ti-6AI-4V, Produtos de desgate, Vanádio, Efeitos biológicos, Wear products, Vanadium, Biological effects