Cimentos injetáveis à base de fosfatos de cálcio para vertebroplastia

O principal objectivo desta investigação foi o desenvolvimento cimentos de fosfatos de cálcio com injetabilidade melhorada e propriedades mecânicas adequadas para aplicação em vertebroplastia. Os pós de fosfato de tricálcico (TCP) não dopados e dopados (Mg, Sr e Mn) usados neste estudo foram obtidos pelo processo de precipitação em meio aquoso, seguidos de tratamento térmico de forma a obter as fases pretendidas, α− e β−TCP. A substituição parcial de iões Ca por iões dopantes mostrou ter implicações em termos de estabilidade térmica da fase β−TCP. Os resultados demonstraram que as transformações de fase alotrópicas β↔α−TCP são fortemente influenciadas por variáveis experimentais como a taxa de arrefecimento, a presença de impurezas de pirofosfato de cálcio e a extensão do grau de dopagem com Mg. Os cimentos foram preparados através da mistura de pós, β−TCP (não dopados e dopados) e fosfato monocálcico monidratado (MCPM), com meios líquidos diferentes usando ácido cítrico e açucares (sucrose e frutose) como agentes retardadores de presa, e o polietilenoglicol, a hidroxipropilmetilcelulose e a polivinilpirrolidona como agentes gelificantes. Estes aditivos, principalmente o ácido cítrico, e o MCPM aumentam significativamente a força iónica do meio, influenciando a injetabilidade das pastas. Os resultados também mostraram que a distribuição de tamanho de partícula dos pós é um factor determinante na injetabilidade das pastas cimentícias. A combinação da co-dopagem de Mn e Sr com a adição de sucrose no líquido de presa e com uma distribuição de tamanho de partícula dos pós adequada resultou em cimentos de brushite com propriedades bastante melhoradas em termos de manuseamento, microestrutura, comportamento mecânico e biológico: (i) o tempo inicial de presa passou de ~3 min to ~9 min; (ii) as pastas cimentícias foram totalmente injectadas para uma razão liquido/pó de 0.28 mL g−1 com ausência do efeito de “filter-pressing” (separação de fases líquida e sólida); (iii) após imersão numa solução durante 48 h, as amostras de cimento molhadas apresentam uma porosidade total de ~32% e uma resistência a compressão de ~17 MPa, valor muito superior ao obtido para os cimentos sem açúcar não dopados (5 MPa) ou dopados só com Sr (10 MPa); e (iv) o desempenho biológico, incluindo a adesão e crescimento de células osteoblásticas na superfície do cimento, foi muito melhorado. Este conjunto de propriedades torna os cimentos excelentes para regeneração óssea e engenharia de tecidos, e muito promissores para aplicação em vertebroplastia.

Hybrid materials for biomedical applications

The increased longevity of humans and the demand for a better quality of life have led to a continuous search for new implant materials. Scientific development coupled with a growing multidisciplinarity between materials science and life sciences has given rise to new approaches such as regenerative medicine and tissue engineering. The search for a material with mechanical properties close to those of human bone produced a new family of hybrid materials that take advantage of the synergy between inorganic silica (SiO4) domains, based on sol-gel bioactive glass compositions, and organic polydimethylsiloxane, PDMS ((CH3)2.SiO2)n, domains. Several studies have shown that hybrid materials based on the system PDMS-SiO2 constitute a promising group of biomaterials with several potential applications from bone tissue regeneration to brain tissue recovery, passing by bioactive coatings and drug delivery systems. The objective of the present work was to prepare hybrid materials for biomedical applications based on the PDMS-SiO2 system and to achieve a better understanding of the relationship among the sol-gel processing conditions, the chemical structures, the microstructure and the macroscopic properties. For that, different characterization techniques were used: Fourier transform infrared spectrometry, liquid and solid state nuclear magnetic resonance techniques, X-ray diffraction, small-angle X-ray scattering, smallangle neutron scattering, surface area analysis by Brunauer–Emmett–Teller method, scanning electron microscopy and transmission electron microscopy. Surface roughness and wettability were analyzed by 3D optical profilometry and by contact angle measurements respectively. Bioactivity was evaluated in vitro by immersion of the materials in Kokubos’s simulated body fluid and posterior surface analysis by different techniques as well as supernatant liquid analysis by inductively coupled plasma spectroscopy. Biocompatibility was assessed using MG63 osteoblastic cells. PDMS-SiO2-CaO materials were first prepared using nitrate as a calcium source. To avoid the presence of nitrate residues in the final product due to its potential toxicity, a heat-treatment step (above 400 °C) is required. In order to enhance the thermal stability of the materials subjected to high temperatures titanium was added to the hybrid system, and a material containing calcium, with no traces of nitrate and the preservation of a significant amount of methyl groups was successfully obtained. The difficulty in eliminating all nitrates from bulk PDMS-SiO2-CaO samples obtained by sol-gel synthesis and subsequent heat-treatment created a new goal which was the search for alternative sources of calcium. New calcium sources were evaluated in order to substitute the nitrate and calcium acetate was chosen due to its good solubility in water. Preparation solgel protocols were tested and homogeneous monolithic samples were obtained. Besides their ability to improve the bioactivity, titanium and zirconium influence the structural and microstructural features of the SiO2-TiO2 and SiO2-ZrO2 binary systems, and also of the PDMS-TiO2 and PDMS-ZrO2 systems. Detailed studies with different sol-gel conditions allowed the understanding of the roles of titanium and zirconium as additives in the PDMS-SiO2 system. It was concluded that titanium and zirconium influence the kinetics of the sol-gel process due to their different alkoxide reactivity leading to hybrid xerogels with dissimilar characteristics and morphologies. Titanium isopropoxide, less reactive than zirconium propoxide, was chosen as source of titanium, used as an additive to the system PDMS-SiO2-CaO. Two different sol-gel preparation routes were followed, using the same base composition and calcium acetate as calcium source. Different microstructures with high hydrophobicit were obtained and both proved to be biocompatible after tested with MG63 osteoblastic cells. Finally, the role of strontium (typically known in bioglasses to promote bone formation and reduce bone resorption) was studied in the PDMS-SiO2-CaOTiO2 hybrid system. A biocompatible material, tested with MG63 osteoblastic cells, was obtained with the ability to release strontium within the values reported as suitable for bone tissue regeneration.