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[EN] Zinc is an essential element with an important role in stimulating the osteogenesis and mineralization and suppressing osteoclast differentiation. In this study, new bioactive ZnCl2-doped sol-gel materials were designed to be applied as coatings onto titanium. The biomaterials were physicochemically characterized and the cellular responses evaluated in vitro using MC3T3-E1 osteoblasts and RAW264.7 macrophages. The effect of Zn on the adsorption of human serum proteins onto the material surface was evaluated through nLC-MS/MS. The incorporation of Zn did not affect the crosslinking of the sol-gel network. A controlled Zn2+ release was obtained, reaching values below 10 ppm after 21 days. The materials were no cytotoxic and lead to increased gene expression of ALP, TGF-beta, and RUNX2 in the osteoblasts. In macrophages, an increase of IL-1 beta, TGF-beta, and IL-4 gene expression was accompanied by a reduced TNF-alpha liberation. Proteomic results showed changes in the adsorption patterns of proteins associated with immunological, coagulative, and regenerative functions, in a Zn dose-dependent manner. The variations in protein adsorption might lead to the downregulation of the NF-kappa B pathway, thus explain the observed biological effects of Zn incorporation into biomaterials. Overall, these coatings demonstrated their potential to promote bone tissue regeneration.

[EN] It is known strontium can both inhibit the osteoclast formation and stimulate the osteoblast maturation, so biomaterials containing this element can favour bone structure stabilisation. The addition of Sr to biomaterials could affect their interactions with proteins and cells. Here, a silica-hybrid sol-gel network doped with different amounts of SrCl2 and applied as coatings on titanium discs was examined. in vitro analysis was performed to determine the potential effect of Sr in the coatings, showing enhanced gene expression of osteogenic markers (alkaline phosphatase and transforming growth factor-beta) in MC3T3-E1 incubated with Sr-doped biomaterials. The examination of inflammatory markers (tumour necrosis factor-alpha and interleukin 10) in RAW 264.7 macrophages revealed an anti-inflammatory potential of these materials. Proteins adsorbed onto the coatings incubated with human serum (3 h at 37 degrees C) were also analysed; mass spectrometry was used to characterise the proteins adhering to materials with different Sr content. Adding Sr to the coatings increased their affinity to APOE and VTNC proteins (associated with anti-inflammatory and osteogenic functions). Moreover, the proteins involved in coagulation processes, such as prothrombin, were more abundant on the coatings containing Sr than on the base sol-gel surfaces. Correlations between gene expression and proteomic results were also examined.

[EN] One of the events occurring when a biomaterial is implanted in an host is the protein deposition onto its surface, which might regulate cell responses. When a biomaterial displays a compromised biocompatibility, distinct complement pathways can be activated to produce a foreign body reaction. In this article, we have designed different types of biomaterial surfaces to study the inflammation process. Here, we used different concentrations of (3-glycidoxypropyl)-trimethoxysilane (GPTMS), an organically-modified alkoxysilane as a precursor for the synthesis of various types of sol-gel materials functionalizing coatings for titanium implants to regulate biological responses. Our results showed that greater GPTMS surface concentrations induced greater secretion of TNF-alpha and IL-10 on RAW 264.7 macrophages. When implanted into rabbit tibia, osseointegration decreased with higher GPTMS concentrations. Interestingly, higher deposition of complement-related proteins C-reactive protein (CRP) and ficolin-2 (FCN2), two main activators of distinct complement pathways, was observed. Taking all together, inflammatory potential increase seems to be GPTMS concentration-dependent. Our results show that a greater adsorption of complement proteins can condition macrophage polarization.

[EN] Calcium is an element widely used in the development of biomaterials for bone tissue engineering as it plays important roles in bone metabolism and blood coagulation. The Ca ions can condition the microenvironment at the tissue-material interface, affecting the protein deposition process and cell responses. The aim of this study was to analyze the changes in the patterns of protein adsorption on the silica hybrid biomaterials supplemented with different amounts of CaCl2, which can function as release vehicles. This characterization was carried out by incubating the Ca-biomaterials with human serum. LC-MS/MS analysis was used to characterize the adsorbed protein layers and compile a list of proteins whose affinity for the surfaces might depend on the CaCl2 content. The attachment of pro- and anti-clotting proteins, such as THRB, ANT3, and PROC, increased significantly on the Ca-materials. Similarly, VTNC and APOE, proteins directly involved on osteogenic processes, attached preferentially to these surfaces. To assess correlations with the proteomic data, these formulations were tested in vitro regarding their osteogenic and inflammatory potential, employing MC3T3-E1 and RAW 264.7 cell lines, respectively. The results confirmed a Ca dose-dependent osteogenic and inflammatory behavior of the materials employed, in accordance with the protein attachment patterns.

To avoid dental implant-related infections and to promote the osseointegration of titanium implants, the application of silicon and chitosan containing coatings is proposed. Silicon is a well-known osteogenic element and chitosan was selected to confer the antibacterial properties. The synthesis of hybrid silica-chitosan coatings using the sol-gel process is presented and the characterization using Si-NMR to verify the correct formation of the network is discussed. The C NMR spectroscopy was used to confirm the covalent union between chitosan and the silicon network. Hydrolytic degradation and silicon release studies showed the effective silicon release from the hybrids and, hence, the possibility to promote bone formation. The introduction of different amounts of chitosan and tetraethyl orthosilicate (TEOS) modulated the Si release. The analysis of cell cultures in vitro demonstrated that the hybrid coatings were not cytotoxic and promoted cell proliferation on their surfaces. The coatings containing 5%–10% chitosan had substantial antibacterial properties.

Human bacterial pathogens found on medical implants are one of the main causes of morbidity and mortality, making the development of novel coatings the primary strategy in the prevention of medical device-associated infections. Here, we describe organic-inorganic hybrid coatings for metallic bone implants, based on sol-gel materials of proven osteogenic capacity. The coatings were doped with two bactericides: octenidine dihydrochloride (OCT) and chlorhexidine diacetate (CHX). These bactericides, known for their efficiency, are widely used in the prevention and elimination of bacterial infections. The coatings have good chemical and mechanical properties, making them suitable for use on medical devices. They also demonstrate strong antibacterial capacity, dependent on the concentration of the bactericide. They are not toxic to human osteoblasts. Our results suggest this system as a tool for coating medical devices to prevent bacterial infections.

Se han formulado cementos óseos acrílicos inyectables para su uso en vertebroplastia (VP) y se les ha proporcionado bioactividad mediante la incorporación de sales de hidroxiapatita estroncio (HASr). El objetivo es combinar la fijación inmediata que proporciona el cemento acrílico, con la fijación a largo plazo que proporciona la HASr. Además, la presencia de Sr en la carga proporciona radiopacidad, con lo cual se evita la adición de agentes radiopacos adicionales. Así, se estudió el efecto de la incorporación de la HASr en las propiedades del cemento óseo. La adición se realizó en la fase sólida de 2 modos diferentes: en polvo, tal como se obtiene tras la síntesis y después de un sencillo tratamiento superficial con monómero. Los resultados muestran que el tratamiento mejora la mojabilidad de las partículas, lo que mejora la inyección de estos cementos y proporciona propiedades mecánicas superiores, sin perjudicar al contenido de monómero residual. La formulación de cemento idónea para VP sería la que contiene un 20% de HASr tratada, ya que presenta una inyectabilidad mejorada, elevada radiopacidad, la mayor bioactividad y además, la mejora de propiedades mecánicas es significativa.

Se han formulado cementos óseos acrílicos inyectables para su uso en vertebroplastia (VP) y se les ha proporcionado bioactividad mediante la incorporación de sales de hidroxiapatita estroncio (HASr). El objetivo es combinar la fijación inmediata que proporciona el cemento acrílico, con la fijación a largo plazo que proporciona la HASr. Además, la presencia de Sr en la carga proporciona radiopacidad, con lo cual se evita la adición de agentes radiopacos adicionales. Así, se estudió el efecto de la incorporación de la HASr en las propiedades del cemento óseo. La adición se realizó en la fase sólida de 2 modos diferentes: en polvo, tal como se obtiene tras la síntesis y después de un sencillo tratamiento superficial con monómero. Los resultados muestran que el tratamiento mejora la mojabilidad de las partículas, lo que mejora el mezclado de estos cementos y proporciona propiedades mecánicas superiores. La formulación de cemento idónea para VP sería la que contiene un 20% de HASr tratada, ya que presenta una elevada radiopacidad, la mayor bioactividad y además, la mejora de propiedades mecánicas es significativa., Bioactive and injectable bone cements designed to perform vertebroplasty (VP) have been prepared by adding strontium hydroxyapatite (SrHA) to a formulation based on methylmethacrylate. Thus, the cement combines the immediate support given by the setting of the acrylic matrix, with the long term integration due to the incorporation of the SrHA. Moreover, the presence of Strontium makes this filler highly radiopaque, which avoids the undesirable and extended practice of the addition of more radiopaque substances by the surgeon. For that purpose, the effect of the addition of SrHA particles, incorporated ‘as synthetised’ and after a surface treatment with the monomer, was studied on various properties of the cement. Results showed that the surface treatment improved the wettability of the SrHA particles, and, as a consequence, the mixing and the mechanical properties. The best formulation to perform VP is 20%-treated SrHA containing formulation, which shows enhanced mechanical properties compared with control formulations, along with high radiopacity and the higher bioactivity.

In a previous work, we reported the development of acrylic bone cement formulations for application in percutaneous vertebroplasty, by using bismuth salicylate (BS) as the radiopaque agent. Our objective was to obtain high radiopacity along with a therapeutical effect produced by the release of salicylic acid in situ. To follow that study, the setting kinetics and static and dynamical mechanical properties of the BS cements were studied in simulated physiological conditions. Moreover, radiopacity after various times of immersion in saline and the wettability of the cements surfaces were determined. The study finished with the analysis of the biological response. From the results, it can be concluded that physiological conditions did not affect negatively to the cements performance, since all BS-loaded cements fulfilled the ISO standard requirements. Radiopacity of the formulations was maintained over time and cements with BS were found to be biocompatible

Hydrogels based on ethoxytriethyleneglycol monomethacrylatelmethyl methacrylate copolymers were prepared by free radical polymerization at 70°C in bulk with 2,2’-azobisisobutyronitrile as initiator. The swelling behaviour of the hydrogels was studied by immersion of the films in water and in buffered solutions at various pHs. The hydration process was followed gravimetrically measuring the water uptake of the films with the time of treatment. The kinetics fit adequately a Fickian law for reduced sorption coefficients, M,/M,, lower than 0.6. The values of the diffusion coefficient were lower at neutral pH than at acidic or alkaline pHs, and they seemed to be independent of the copolymer composition. The results obtained were consistent with the stress relaxation model of polymer chains predicted for a relatively fast hydration process. The swelling process is reversible and the polymeric films are stable after repeating cycles of hydration and desorption promoted by the change of pH in appropriate buffered solutions.