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Biomedical subjects

M Vallet-Regí

Publications and source records attributed to M Vallet-Regí.

At least 19 recordsLinked to original sources

Bioactive glasses as accelerators of apatite bioactivity.

Synthetic carbonatehydroxyapatite is the ceramic closest to the mineral component of human bone and seems, therefore, the optimum material to use in osseous implants. However, in vitro assays performed to determine its bioactivity have shown no positive results after 2 months of assay. With the aim of improving this bioactivity, a new biphasic material was synthesized composed mainly of synthetic carbonatehydroxyapatite and only 5% of a sol-gel bioactive glass. In vitro assays were assessed to determine the bioactive behavior of this new material and revealed that the addition of a minimal amount of bioactive glass is enough to induce bioactivity on synthetic carbonatehydroxyapatites.

Apatites↗

In vitro bioactivity of silicon-substituted hydroxyapatites.

Silicon-containing hydroxyapatites were synthesized by the controlled crystallization method. Chemical analysis, N(2) adsorption, Hg porosimetry, X-ray diffraction, scanning electron microscopy-energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy (XPS) were used to characterize the hydroxyapatite and to monitor the development of a calcium phosphate layer onto the surface of the substrate immersed in a simulated body fluid, that is, in vitro bioactivity tests. The influence of the silicon content and the nature of the starting calcium and phosphorus sources on the in vitro bioactivity of the resulting materials were studied. A sample of silicocarnotite, whose structure is related to that of hydroxyapatite and contains isolated SiO(4) (4-) anions that isomorphically substitute some PO(4) (3-) anions, was prepared and used as reference material for XPS studies. An increase of the unit cell parameters with the Si content was observed, which indicated that SiO(4) (4-) units are present in lattice positions, replacing some PO(4) (3-) groups. By using XPS it was possible to assess the presence of monomeric SiO(4) (4-) units in the surface of apatite samples containing 0.8 wt % of silicon, regardless the nature of the starting raw materials, either Ca(NO(3))(2)/(NH(4))(2)HPO(4)/Si(OCOCH(3))(4) or Ca(OH)(2)/H(3)PO(4)/Si(OCOCH(3))(4). However, an increase of the silicon content up to 1.6 wt % leads to the polymerization of the silicate species at the surface. This technique shows silicon enrichment at the surface of the three samples. The in vitro bioactivity assays showed that the formation of an apatite-like layer onto the surface of silicon-containing substrates is strongly enhanced as compared with pure silicon-free hydroxyapatite. The samples containing monomeric silicate species showed higher in vitro bioactivity than that of silicon-rich sample containing polymeric silicate species. The use of calcium and phosphate salts as precursors lead to materials with higher bioactivity.

Calcium↗

A new quantitative method to evaluate the in vitro bioactivity of melt and sol-gel-derived silicate glasses.

Two melt-derived glasses (45S5 and 60S) and four sol-gel glasses (58S, 68S, 77S, and 91S) have been synthesized. The activation energy for the silicon release was determined, and a very close correlation was observed between this value and published results of the bioactive behavior of the glasses. This relationship can be explained in terms of the influence of chemical composition, textural properties, and structural density on the silanol group formation and silicon dissolution. These measurements provide a quantitative method to evaluate the in vitro bioactivity of SiO(2)-based glasses. Preliminary studies suggest an activation energy gap (Ea) of 0.35-0.5 eV as a boundary between bioactive and nonbioactive glasses.

Biocompatible Materials↗

In vivo bone response to porous calcium phosphate cement.

We conducted an in vivo experiment to evaluate the resorption rate of a calcium phosphate cement (CPC) with macropores larger than 100 microm, using the CPC called Biocement D (Merck Biomaterial, Darmstadt, Germany), which after setting only shows pores smaller than 1 microm. The gas bubble method used during the setting process created macroporosity. Preset nonporous and porous cement implants were inserted into the trabecular bone of the tibial metaphysis of goats. The size of the preset implants was 6 mm and the diameter of the drill hole was 6.3 mm, leaving a gap of 0.3 mm between implant surface and drill wall. After 2 and 10 weeks, the animals were euthanized and cement implants with surrounding bone were retrieved for histologic evaluation. Light microscopy at 2 weeks revealed that the nonporous implants were surrounded by connective tissue. On the cement surface, we observed a monolayer of multinucleated cells. Ten weeks after implantation, the nonporous implants were still surrounded by connective tissue. However, a thin layer of bone now covered the implant surface. No sign of cement resorption was observed. In contrast, the porous cement evoked a completely different bone response. At 2 weeks, bone formation had already occurred inside the implant porosity. Bone formation even appeared to occur as a result of osteoinduction. Also, at their outer surface, the porous implants were completely surrounded by bone. At 2 weeks, about 31% of the initial cement was resorbed. After 10 weeks, 81% of the initial phosphate cement was resorbed and new bone was deposited. On the basis of these observations, we conclude that the creation of macropores can significantly improve the resorption rate of CPC. This increased degradation is associated with almost complete bone replacement.

Animals↗

Biphasic materials for bone grafting and hyperthermia treatment of cancer.

Three biphasic materials have been synthesized from a magnetic glass-ceramic (Si-Ca-Fe) and a bioactive sol-gel glass (Si-P-Ca). The ratios of glass-ceramic:sol-gel glass used in this work were 1:1, 2:1, and 5:1. These materials show bioactive and magnetic properties and can be used as thermoseeds for hyperthermia treatment of bone tumors. The sol-gel glass content affects the textural properties of the glass-ceramic, giving rise to porosity, which plays a fundamental role in the formation of an apatite-like layer on the surface. On the other hand, as the sol-gel glass content increases, the magnetic properties change due to the diffusion of Fe ions to the glassy phases of the biphasic materials. The biphasic nature of these materials allows the changing of both properties, depending on the requirements of the patient.

Adsorption↗

Bioactive glass-polymer materials for controlled release of ibuprofen.

The ibuprofen (IB) release from samples composed by SiO2-CaO-P2O5 bioactive glass, poly-L-lactic acid (PLA), and polymethylmethacrylate (PMMA) has been studied. Data showed a fast anti-inflammatory drug release during the first 8h when these polyphasic materials are soaked in simulated body fluid (SBF). The analysis of the samples before and after different soaking periods in SBF demonstrates the growth of an apatite-like layer on the materials surface. The IB release rate is related with the growth kinetics of this layer, that is slower when the materials do not contain the biodegradable polymer PLA. On the other hand, different IB and/or glass contents do not affect the in vitro behavior of these materials.

Apatites↗

In vitro release of gentamicin from OHAp/PEMA/PMMA samples.

The influence of hydroxyapatite (OHAp) and gentamicin sulphate (GEN) contents on the release kinetics of GEN, in samples composed of OHAp, poly(methyl methacrylate) (PMMA) and poly(ethyl methacrylate) (PEMA) has been studied. For this purpose, samples with 30 and 40% of OHAp and 5 and 9% of GEN were prepared. The in vitro release study was carried out soaking the samples in simulated body fluid (SBF) at 37 degrees C for 70 days. The release profiles showed a faster release during the first 10 h, diminishing progressively until the end of the study. It was noticed that the percentage of released GEN increased with the OHAp content. For samples with 40% of OHAp, GEN release is nearly independent of the initial amount of such drug (in the range 5-9%), whereas for samples with 30% of OHAp, the release process is favoured by higher contents of GEN, which would favour a higher SBF uptake. GEN release is related to SBF uptake, which is in turn related, on the one hand, to the OHAp content (increase of the porosity and the hydrophilic character of the samples) and on the other hand, to content of GEN.

Delayed-Action Preparations↗

Bioactivity of three CaO-P2O5-SiO2 sol-gel glasses.

Three gel glasses containing 25 mol % of CaO and SiO(2) + P(2)O(5) contents (in mol %): 75 + 0 (S75); 72.5 + 2.5 (S72.5P2.5); and 70 + 5 (S70P5), respectively, were obtained, characterized, and studied when soaked in a simulated body fluid (SBF). The influence of composition in both textural properties (surface area and porosity) and in vitro behavior of glasses was studied. In as prepared S72.5P2.5 and S70P5 glasses, crystalline phosphate nuclei were detected through XRD and FTIR. In addition, N(2) adsorption and Hg porosimetry measurements showed that the surface area increased, whereas the pore volume and the pore diameter decreased as P(2)O(5) in glasses increased. These variations were explained on the basis of the withdrawal of calcium from the glass silica network, due to the calcium-phosphorous bonding. In vitro studies showed that the three compositions were bioactive, because an apatite layer was formed after soaking in SBF. S75 presented the highest initial reactivity but the lowest crystallization rate of the apatite-like phase. For S72.5P2.5, and S70P5 the amorphous calcium phosphate formation was slower than for S75, but the crystallization of apatite was observed after shorter periods in SBF. Furthermore, after 7 days of soaking, the layer thickness decreased as P(2)O(5) in glasses increased.

Apatites↗

Biocompatibility and in vivo gentamicin release from bioactive sol-gel glass implants.

Biomaterial pieces, with suitable osteogenic properties for use in the treatment of bone defects and the capability to avoid bone infections, have been synthesized. These materials are composed exclusively of gentamicin sulfate and bioactive SiO(2)-CaO-P(2)O(5) sol-gel glass (previously synthesized). Implant processing was achieved by uniaxial and isostatic pressure of the components mixture. After implanting the pieces into rabbit femur, we studied (i) the antibiotic release, determining the concentration in proximal and distal bone, liver, kidney, and lung as a function of time; and (ii) the bone growth resulting from the glass reactivity in the biologic environment. The results indicate that the implants are good carriers for local gentamicin release in the osseous tissue, exhibiting excellent biocompatibility and bone integration. Moreover, these implants are able to promote bone growth during their resorption process.

Animals↗

Fabrication of porous hydroxyapatite bodies by a new direct consolidation method: starch consolidation.

A new direct consolidation method known as "starch consolidation" was developed especially for the fabrication of porous ceramics, as adopted to prepare hydroxyapatite (OHAp) bodies with different pore sizes and pore volume fractions. The method is based on the swelling ability of starch when it is heated to 80 degrees C in the presence of water. An OHAp powder prepared by a precipitation method and heat treated at 900 degrees C to obtain an appropriate specific surface area for colloidal processing was used in the present work. Wet ball milling was required to deagglomerate the powder and improve its processing ability. Different starch volume fractions and starch particle sizes were added to the OHAp slurries, which were then heat treated to promote consolidation by starch gelification. A linear relationship between the planned and measured porosity values was observed. SEM pictures reveal the presence of interconnected pores with shape and sizes corresponding to starch granules used. Flexural strength varied from about 2 to 15 MPa, for pore volume fractions of approximately 70 and 45%, respectively. A degradation study in an acellular synthetic body fluid (SBF) has shown that the prepared bodies keep their integrity under physiological conditions during the studied time. The method offers possibilities of manufacturing materials that can be used as scaffolds engineering and/or systems for controlled delivery of drugs.

Adsorption↗

Hydroxyapatite ceramic bodies with tailored mechanical properties for different applications.

A perfect control on the final ceramic features will enable the research/clinical community to spread the use of calcium phosphate ceramic bodies to a large number of applications and/or requirements. The mechanical properties of hydroxyapatite ceramic bodies manufactured by different techniques and with different porosities is presented. The flexural strength, hardness, fracture toughness, surface roughness, and their evolution after immersion in SBF are studied. An increase of the mechanical properties with density is observed. The factors governing these results are analyzed. The increase of the porosity percentage of the bodies results in an increase on the surface roughness. The degradation studies show that the HA ceramics keep their integrity and mechanical properties under physiological conditions during the soaking time studied. The OHAp ceramic bodies with controlled porosity could be appropriated for hard tissue substitution or as a carriers for controlled delivery of drugs or as scaffolds for tissue engineering.

Algorithms↗

Preparation and in vitro bioactivity of hydroxyapatite/solgel glass biphasic material.

Hydroxyapatite/solgel glass biphasic material has been obtained in order to improve the bioactivity of the hydroxyapatite (OHAp). A mixture of stoichiometric OHAp and the precursor gel of a solgel glass, with nominal composition in mol% CaO-26, SiO2-70, P205-4, has been prepared. The amounts of components used have been selected to obtain a final relationship for OHAp/solgel glass of 60/40 on heating. Two different thermal treatments have been used: (i) 700 degrees C, temperature of solgel glass stabilisation and (ii) 1000 degrees C, lower temperature of hydroxyapatite sintering. The bioactivity of the resulting materials has been examined in vitro by immersion in simulated body fluid at 37 degrees C. The results obtained show that both materials are bioactive. The apatite-like layer grown is greater for the new materials than for the OHAp and the solgel glass themselves.

Calcium Compounds↗

A novel bioactive and magnetic biphasic material.

A novel biphasic material has been synthetised from a sol-gel-derived glass (Si-Ca-P) and a glass-ceramic obtained from a melt-derived glass (Si-Ca-Fe). Both components of such a biphasic mixture are bioactive, but with different kinetics for the growth of an apatite-like layer on the surface of these materials, needing only one day for the sol-gel-derived glass and one month for the glass-ceramic. The glass-ceramic shows magnetic properties. The biphasic material, obtained from a mixture 1:1 of these components, is bioactive, and its surface is coated after 15 days of soaking in SBF. The biphasic material also exhibited magnetic behaviour, useful for hyperthermia.

Adsorption↗

A new method to produce macropores in calcium phosphate cements.

A new way to create macropores in calcium phosphate cements has been developed. The method consists in adding NaHCO3 to the starting cement powder (Biocement D) and using two different liquids: first a basic liquid to form the paste and later an acid liquid to obtain CO2 bubbles. Mercury intrusion measurements showed a dramatic increase both in macropores with an average size of 100 m and in the total porosity (even higher than 50% with respect to the Biocement D). This method does not change in any significant way the final reaction products of the starting material after being soaked 3 days in Ringer solution. Only, due to the increase of the porosity. the compressive strength of the porous cement decreases significantly.

Biodegradation, Environmental↗

Fabrication of hydroxyapatite bodies by uniaxial pressing from a precipitated powder.

Hydroxyapatite (OHAp) has been obtained by using a precipitation method. Thermal stability of the precipitated powder has been checked to define an appropriate working range to process ceramic bodies without the appearance of odd phases. Pellets of hydroxyapatite have been manufactured by means of uniaxial pressing and convenient thermal treatments have been investigated to achieve high density OHAp bodies. Finally, factors that could affect the ultimate mechanical properties of the sintered bodies prepared by uniaxial pressing have been discussed.

Hydroxyapatites↗

Bioactivity in glass/PMMA composites used as drug delivery system.

Gentamicin sulfate has been incorporated in composites prepared from a SiO2-CaO-P2O5 bioactive glass and polymethylmethacrylate. Data showed that these materials could be used as drug delivery system, keeping the bioactive behavior of the glass. The composites supply high doses of the antibiotic during the first hours when they are soaked in simulated body fluid (SBF). Thereafter, a slower drug release is produced, supplying 'maintenance' doses until the end of the experiment. The gentamicin release rate is related with the ionic Ca2+ and H3O+ exchange between composite and SBF. The porous structure of the composites allows the growth of hydroxycarbonate apatite on the surface and into the pores.

Anti-Bacterial Agents↗

Colloidal processing of hydroxyapatite.

Reliable bioceramics are needed to implement the high requirements that living tissues demand. This work focuses on the processing steps necessary to manufacture advanced ceramics that can be used as implant devices. The influence of the heat treatment temperature on the characteristics of a precipitated hydroxyapatite (OHAp) powder was evaluated in order to obtain an appropriate specific surface area for colloidal processing. Ball milling of the calcined powders for 20 h was required to improve the rheological properties of the suspensions and the packing ability during consolidation. Different dispersing agents were tested and the first trial was made based on their effect on the zeta potential. The most promising ones were then selected and their efficiency was evaluated from rheological measurements and slip-casting performance of suspensions prepared at different solids loading. Targon 1128 was revealed to be the most efficient dispersant, enabling to prepare fluid suspensions containing 50 vol% solids and the highest green and sintered density values to be obtained.

Colloids↗

Static and dynamic in vitro study of a sol-gel glass bioactivity.

A comparative study of in vitro bioactivity of a sol-gel glass with composition 55% SiO2-41%CaO-4%P2O5 has been carried out by soaking it in a simulated body fluid (SBF) with and without exchange of this solution. When SBF is kept constant (static assay) the solution composition changes, increasing the Ca2+ concentration and pH as a function of soaking time while these parameters remain nearly constant and very close to human conditions in dynamic conditions. Glass surface is studied by FTIR, XRD and SEM in order to compare the behaviour in the two procedures, revealing that in both cases an apatite-like layer is formed on the glass surface, although there are differences in rate and morphology in this formation. In addition, a study of porosity was carried out by Hg intrusion pointing out the pore distribution and changes in porosity with time for both procedures. A similar behaviour in mesopore region was detected, while macropores remain nearly constant in static conditions, decreasing from 0.48 to 0.12 microm in just 3 h of soaking in dynamic assay.

Apatites↗