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Hydroxy-fluorapatites (OH-FAps) occur biologically in teeth and form the basis for application as biomaterials. This work aims to synthesize a series of fluoride substituted calcium hydroxyapatites (OHAps) to determine how fluoride influences the synthesis and the resulting characteristics of solid solutions. OH-FAPs powders were synthesized with a chemical composition of Ca(10)(PO(4))(6)(OH)(2-x) F(x), with x=0.0, 0.4, 0.8, 1.2, 1.6 and 2.0. The synthesis of partially substituted OHAp yields materials with lower crystallinity and higher specific surface area than OHAp or fluorapatite (FAp). The smallest crystal size of 263A, occurs at less than 50% hydroxyl substitution with fluoride at x=0.4, and the highest surface area of 132m(2)/g occurs at x=0.8. Reaction kinetics occur faster at higher fluoride content, producing the expected Ca/P ratio of 1.67 only for x=2.0. X-ray and IR studies show that OH-FAPs are homogeneous solid solutions instead of mixtures of OHAp and FAp. The presence of a high fluoride concentration increases the driving force for crystal growth during the calcination process.

X-ray diffraction (XRD) patterns of hydroxyfluorapatites with a nominal composition of Ca10(PO4)6(OH)2-xFx, where x = 0.0, 0.4, 0.8, 1.2, 1.6, and 2.0, were collected and analyzed using the Rietveld method. A multiphase Rietveld analysis performed on calcined samples reveals a range of Ca/P ratios from 1.56 for the sample with x = 0.4 to 1.67 for the sample with x = 2.0 on the synthesized powders. Calcined apatites exhibit a decrease in the lattice parameter a, a greater crystallite size, lower distortion in the phosphate tetrahedra, and greater stability of the apatite structure for higher fluoride contents.

The layering of fluorapatite on hydroxyapatite bodies provides a means of decreasing the solubility of hydroxyapatite, providing fluoride for possible stimulation of bone formation and delaying the release of calcium and phosphate from the more soluble hydroxyapatite. The purpose of this work was to encapsulate hydroxyapatite particles with fluorapatite spanning a thickness more than several crystallites deep. A three-step procedure was employed. Hydroxyapatite powder was immersed in an electrolyte solution until an equilibrium was established between the solid and the dissolved calcium at pH 4.67 and 37 °C. Equilibrium was determined by measurement of dissolved calcium with a calcium-specific ion-specific electrode. A 5×10−2 M ammonium fluoride added to the suspension resulted in a rapid decrease of both calcium and fluoride in the solution. Analysis with X-ray diffraction indicated that a fluoride rich layer containing calcium fluoride deposited onto the particle surface. Scanning electron microscopy revealed submicron spherical precipitate clusters on the hydroxyapatite particles. These clusters transformed to fluorapatite by soaking in a 0.1 M K2HPO4 solution at pH 8 and 70 °C. A total time of 10 h was necessary for complete transformation of CaF_2 into fluorapatite.

The transformation of calcium sulfate hemihydrate into gypsum via reaction with water has been used for many years to produce materials for bone augmentation. In this work, a mixture of CaSO4·1/2H2O and hydroxyapatite was prepared, and its behavior as cement was studied and compared with that of pure calcium sulfate hemihydrate. The setting process was monitored with Gillmore needles, X-ray diffraction, and differential scanning calorimetry. The utilization of the mixture allows one to prepare homogeneous pastes with better manipulation characteristics than pure calcium sulfate hemihydrate. The workability and setting time of the hydroxyapatite-containing cements are higher than those of pure CaSO4·1/2H2O. The different techniques employed allow us to relate the initial setting time with the chemical transformation of the calcium sulfate hemihydrate into calcium sulfate dihydrate. The biphasic specimens show an improved bioactivity response compared to pure hydroxyapatite or gypsum when soaked in a simula...

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.

The aims of this paper are: (1) to review the current state of the art in the field of cartilage substitution and regeneration; (2) to examine the patented biomaterials being used in preclinical and clinical stages; (3) to explore the potential of polymeric hydrogels for these applications and the reasons that hinder their clinical success. The studies about hydrogels used as potential biomaterials selected for this review are divided into the two major trends in tissue engineering: (1) the use of cell-free biomaterials; and (2) the use of cell seeded biomaterials. Preparation techniques and resulting hydrogel properties are also reviewed. More recent proposals, based on the combination of different polymers and the hybridization process to improve the properties of these materials, are also reviewed. The combination of elements such as scaffolds (cellular solids), matrices (hydrogel-based), growth factors and mechanical stimuli is needed to optimize properties of the required materials in order to facilitate tissue formation, cartilage regeneration and final clinical application. Polymer combinations and hybrids are the most promising materials for this application. Hybrid scaffolds may maximize cell growth and local tissue integration by forming cartilage-like tissue with biomimetic features, This work was supported by SIP-IPN 20170510 Project (Mexico), DGICYT Project, MAT2014-51918-C2-I-R (Spain), (CONACYT/CSIC)-EMHE program through project No. MHE200011 (Mexico-Spain). DA Sánchez-Téllez also acknowledges CONACYT (Mexico) for the scholarship given. The authors acknowledge Stephanie Cisneros-Téllez for helping them in the digitalization of Figures 1, 4 and 8.

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.

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.

The growing necessity of biomaterials has increased the interest in calcium phosphates, particularly apatites. Small differences in stoichiometry, crystallinity, morphology, etc. could contribute to the different clinical behaviors observed, so perfect control of the synthesis parameters and their influence in the characteristics of the samples is a must. In the present work, a crystallization set able to produce massive and reproducible quantities of different calcium phosphates is presented. Apatites with different stoichiometries and morphologies are prepared, and the effects of varying synthesis conditions are analyzed. Temperatures in the range 25−37 °C are necessary to obtain apatites with crystal sizes in the range of adult human bone. Longer reaction times produce increased Ca/P ratios. Aging of the precipitated powder can lead to the incorporation of minor quantities of carbonate. It is possible to force the incorporation of carbonate ions into the apatitic structure without introducing monovalen...

Pechini method is a materials synthesis method based on the preparation of a polymeric matrix. The advantage of this method is the ability to obtain materials with different particle sizes depending on the synthesis condition with a homogeneous distribution. In this work, carbonated hydroxyapatite (c-OHAp) nanoparticles were obtained by a modified Pechini method. To obtain the polymeric precursor of the c-OHAp, the polymeric matrix was prepared through a polyesterification reaction between citric acid and ethylene-glycol. Adding calcium hydroxide and ortophosphoric acid in aqueous solutions, raising the temperature up to 140 C/2 h and keeping constant the pH at 8. The polymeric matrix was calcinated at different ranges of temperature from 200 to 600 C in order to obtain the c-OHAp powder. The results show the presence of c-OHAp a as unique phase. The thermal analysis indicates that the c-OHAp phase was obtained at 600 C. The particle size of the obtained material was\50 nm

Composite biomaterials with good mechanical response and a partially biodegradable character were prepared by the free radical polymerization of mixtures of α-Al 2 O 3 , low-molecular-weight but crystalline poly(L-lactic acid) (PLLA), and methyl methacrylate (MMA). Cylindrical specimens prepared with different composition were characterized by thermogravimetry, calorimetry, 1 H-NMR spectroscopy, and x-ray diffraction (XRD). The in vitro biodegradative process was studied in different media, following variations of the pH, gravimetric weight loss of the specimens, and crystalline domain change by XRD after immersion in pure water and buffered solutions at pH 4.0 and pH 8.0 for 90 days. Formation of a relatively porous structure with good cohesion after the biodegradative treatment (confirmed by SEM) was observed. These systems can be considered for applications in orthopedic surgery as filling biomaterials and even as control drug-delivery systems.

The purpose of this work is to evaluate how the surface modification of apatites with alendronate may affect the adsorption of proteins relevant for bone regeneration. Two different apatites were synthesized for the study. Both of the powders were obtained by co-precipitation, assisted either by mechanical or by ultrasonic stirring. Hydroxyapatite-alendronate hybrid compounds were obtained by reactive milling and the protein adsorption experiments were done by mixing 10 mg of the hydroxyapatites and hybrids powders with 1.5 mL of a 0.1 mg/mL fibronectin solution. After 24h of digestion and separation of the solid from the liquid, the protein remaining in the liquid was measured by UV/VIS Spectrometry. The formation of the hybrids has been confirmed by the shift of significant Raman bands assigned to νP-O(H) and δP-OH bands that indicates changes in the P-O bond of the alendronate due to different modes of coordination to the Ca2+ ion of the apatite. Hybrids materials adsorb less fibronectin than their corresponding hydroxyapatite precursors.

Composite materials are very promising biomaterials for hard tissue augmentation. The approach assayed in this work involves the manufacturing of a composite made of a bioactive ceramic, natural wollastonite (W) and a nanostructured copolymer of ethylmethacrylate (EMA) and vinylpyrrolidone (VP) to yield a bioresorbable and biocompatible VP–EMA copolymer. A bulk polymerization was induced thermally at 508C, using 1 wt % azobis(isobutyronitrile) (AIBN) as free-radical initiator. Structural characterization, compressive strength, flexural strength (FS), degradation, bioactivity, and biocompatibility were evaluated in specimens with a 60/40 VP/EMA ratio and ceramic content in the range 0–60%. A good integration between phases was achieved. Greater compression and FS, in comparison with the pure copolymer specimens was obtained only when the ceramic load got up to 60% of the total weight. The soaking in NaCl solution resulted in the initial swelling of the specimens tested. The maximum swelling was reached after 2–3 h of immersion and it was significantly greater for lower ceramic loads. This result makes the polymer component the main responsible for the interactions with the media. After soaking in SBF, microdomains segregation can be observed in the polymer component that can be related with a dramatic difference in the reactivity of both monomers in free radical polymerization, whereas the formation of an apatite-like layer on the W surfaces can be observed. Biocompatibility in vitro studies showed the absence of cytotoxicity of all formulations. The cells were able to adhere on the polystyrene negative control and on specimens containing 60 wt % wollastonite forming a monolayer and showing a normal morphology. However, a low cellular growth was observed. 2008 Wiley Periodicals, Inc. J Biomed Mater Res 88A: 53–64, 2009

Bisphosphonates (BP) are drugs currently administered orally to treat diseases characterised by an excessive bone resorption. Alternative and more efficient delivery routes and more potent compounds are being investigated. Three implantable delivery systems, which allow the controlled release of therapeutic agents from the device core, are examined in this paper. (4- (aminomethyl) benzene) bisphosphonic acid (ABBP) was incorporated on Ca8.8Na0.8(PO4)4.8(CO3)1.2(OH)0.4F1.6 particles by refluxing the powder in a 60 mmol suspension in acetone at 60ºC for 5 hours. 4-aminophenyl acetic bisphosphonate monosodium salt (APBP) and 1- H-indole-3-acetic bisphosphonate monosodium (IBP) were loaded on Ca10(PO4)6(OH)1F1 ceramic bodies by stirring the ceramic bodies in 0.04M BP solutions. Injectable acrylic cements based on self-curing formulations of methyl methacrylate (MMA) and vitamin E were loaded with APBP and IBP. The incorporation of ABBP was confirmed by MAS-NMR spectroscopy. Modified powder shows two different phosphorous environments, the first one at 2.91 ppm can be assigned to the apatite base and the second one at 18.0 ppm has to be attributed to the phosphonic group of the ABBP. The IBP addition on ceramic surfaces did not decrease the number of osteoclast colonies and appeared to improve the performance of the HA as a surface for osteoblast culture. A therapeutic dosage of APBP and IBP can be achieved from acrylic cements that showed lack of toxicity and an increased cellular activity and proliferation, Financial support from CICYT, Spain (MAT2004-01654) and NoE EXPERTISSUES (UE contract Nº: 500283-2) is acknowledged. Mar Fernández and Luis M. Rodríguez Lorenzo are supported by the Ramón y Cajal Programme, MEC-Spain

En este trabajo se presenta el estudio de la biocompatibilidad in vitro, empleando cultivos celulares de fibroblastos embrionarios humanos, de tres sistemas acrílicos de liberación controlada de bisfosfonatos (BFs). Estos sistemas, basados en metacrilato de metilo (MMA), metacrilato de vitamina E (MVE) y trietilenglicol dimetacrilato (TEGDMA), han sido diseñados para su aplicación en el tratamiento de enfermedades caracterizadas por una elevada resorción osteoclástica. En su preparación se ha empleado un BP comercializado (alendronato; ALN) y dos de nueva síntesis, pertenecientes a la segunda y tercera generaciones, el ácido 1-hidroxi-2-[4-aminofenil]etano-1,1-difosfónico (APBP) y el ácido 1-hidroxi-2-[3-indolil]etano-1,1-difosfónico (IBP), respectivamente. La citotoxicidad de MVE ha sido notablemente inferior a la medida para TEGDMA. La citotoxicidad de APBP e IBP se ha comparado con la de ALN, obteniéndose unos valores para la concentración IC50, de15,56, 9,86 y 6,25 mmol/l para APBP, ALN e IBP, respectivamente. Los niveles de citotoxicidad liberada han sido superiores para la formulación portadora de ALN, situándose a continuación los cementos cargados con IBP y APBP. Cuando los cultivos se han establecido sobre la superficie de las formulaciones, se han detectado unos niveles de proliferación celular y adhesión superiores para los sistemas de liberación de IBP y APBP, siendo además inferior en estos casos la mortalidad celular. This paper reports the in vitro biocompatibility study, using human embryonic fibroblast cultures, of three acrylic systems for controlled release of bisphosphonates (BFs). These systems, that are based on methyl methacrylate (MMA), vitamin E methacrylate (MVE) and triethyleneglycol dimethacrylate (TEGDMA), have been designed for its application in the treatment of pathologies characterized by a high osteoclastic resorption. A commercial BP (alendronate; ALN) and two novel BPs, belonging to the second and third generations, 1-hydroxy-2-[4-aminophenyl]ethane-1,1-diphosphonic acid (APBP) and 1-hydroxy-2-[3-indolyl]ethane-1,1-diphosphonic acid (IBP), respectively, have been used in their preparation. The cytotoxicity of MVE has been notably lower than that measured for TEGDMA. Cytotoxicity of APBP and IBP was evaluated along with that of ALN, and the following values of the IC50, concentration were obtained for APBP, ALN and IBP respectively: 15.56, 9.86 and 6.25 mmol/l. The cytotoxicity levels obtained from the extracts of the cured systems were higher for the formulation containing ALN, followed by the cements loaded with IBP and APBP. When the cultures were seeded directly on the formulations surface, higher levels of cellular proliferation and adhesion were obtained for the systems containing IBP and APBP, the cellular mortality being also inferior in these cases.

Two bisphosphonates (BPs), namely 1-hydroxy-2-[4-aminophenyl]ethane-1,1-diphosphonic acid (APBP) and 1-hydroxy-2-[3-indolyl]ethane-1,1-diphosphonic acid (IBP), have been synthesized and incorporated to acrylic injectable and self-curing formulations. Alendronic acid monosodium trihydrated salt (ALN) containing cement was formulated as control. These systems have potential applications in low density hard tissues affected by ailments characterized by a high osteoclastic resorption, i.e. osteoporosis and osteolysis. Values of curing parameters of APBP and IBP were acceptable to obtain pastes with enough fluency to be injected through a biopsy needle into the bone cavity. Working times ranged between 8 and 15 min and maximum temperature was around 508C. Cured systems stored for a month in synthetic body fluid had compressive strengths between 90 and 96 MPa and modulus between 1.2 and 1.3 GPa, which suggest mechanical stabilization after setting and in the short time. BPs were released in PBS at an initial rate depending on the corresponding chemical structure in the order ALN > APBP > IBP to give final concentrations in PBS of 2.21, 0.44, and 0.19 mol/mL for ALN, APBP, and IBP, respectively. Cytotoxicities of bisphosphonates were evaluated, IC50 values being in the order APBP > ALN > IBP. Absence of cytotoxicity coming from leachables of the cured systems was observed in all cases independently of the BP. An improved cell growth and proliferation for the systems loaded with APBP and IBP compared with that loaded with ALN was observed, as assessed by measuring cell adhesion and proliferation, and total DNA content

The effects of heat treatment time and temperature on the delivery behaviour of Ibuprofen from hydroxyapatite particles were investigated in this study. The drug release was seen to follow Fickian diffusion for the initial period of release for all heat treatment conditions. The gradient of Fickian release increased with (1) increasing crystallite size, attributed to the decreasing amount of boundary area, and (2) with decreasing surface area, due to the reduction in porosity and hence tortuosity within the apatite particles. This study has shown that altering the heat treatment conditions used to calcine hydroxyapatite may alter its drug delivery abilities, whereby calcination temperature was noted to influence the drug release behaviour to a greater extent than calcination time.

Fluoride substitution within hydroxyapatite is an important occurrence for biological apatites and is a promising approach for the chemical modification of synthetic hydroxyapatite. Limited information on the influence of fluoride substitution for hydroxyl groups on the mechanical properties has provided the rationale for this study. Hydroxyfluorapatites with 0%, 20%, 40%, 60%, 80% and 100% replacement of hydroxyl groups with fluoride ions were assessed for hardness, elastic modulus, fracture toughness and brittleness using microindentation of sintered pellets. The production of samples with a similar grain size and density allowed the influence of fluoride on mechanical properties to be determined. It was found that the hardness remains unaffected until 80% replacement of hydroxyl groups with fluoride, after which the hardness rapidly increases. The elastic modulus increases linearly with fluoride content. Fracture toughness is improved with fluoride incorporation into the lattice and reaches a peak of 1.8 for a 95% dense sintered pellet with a 60% fluoride replacement, followed by a rapid decrease at higher fluoride concentrations. The brittleness index is lowered to a minimum at 60%, after which a rapid increase occurs. High fluoride levels are unfavourable from a mechanical perspective, are not recommended for biomaterials, and can lead to a higher incidence of fracture where sodium fluoride, for treatment of osteoporosis, may produce a highly fluoridated hydroxyapatite.

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.

The growing necessity of biomaterials has increased the interest in calcium phosphates, particularly apatites. Small differences in stoichiometry, crystallinity, morphology, etc. could contribute to the different clinical behaviors observed, so perfect control of the synthesis parameters and their influence in the characteristics of the samples is a must. In the present work, a crystallization set able to produce massive and reproducible quantities of different calcium phosphates is presented. Apatites with different stoichiometries and morphologies are prepared, and the effects of varying synthesis conditions are analyzed. Temperatures in the range 25−37 °C are necessary to obtain apatites with crystal sizes in the range of adult human bone. Longer reaction times produce increased Ca/P ratios. Aging of the precipitated powder can lead to the incorporation of minor quantities of carbonate. It is possible to force the incorporation of carbonate ions into the apatitic structure without introducing monovalen...

Fine particles of aluminum oxide (amorphous, α, γ and θ) have been synthesized by spray pyrolysis as a function of both in situ and annealing temperatures and nature of precursors used in the preparation method. A scanning electron micrograph study shows as-received materials constituted by filled spherical particles, the ulterior annealing leading to the formation of small crystallites on the precursor spheres.

Synthetic pseudowollastonite (psW) and a nanostructured copolymer made of a biostable component, Poly(ethylmethacrylate) (PEMA) and a bioresorbable component, vinylpyrrolidone (VP) are used in this work for the preparation of a new family of bone substitutes that allow osseointegration and mechanical stability. Composites are prepared by bulk polymerization of the desired composition in 15 mm diameter cylindrical plastic moulds. Polymerization was induced thermally at 50°C using 1wt% azobis(isobutyronitrile) (AIBN) as free-radical initiator. The moulds were filled to a height of 100 mm and 1 mm height discs were cut with a diamond saw. Specimens with a ceramic/polymer ratio 58/42, 33/67,17/83 and 0/100 were obtained. Compression stress in the range 39-59 MPa and elastic modulus between 2.64 and 4.14 GPa are obtained where the greater values correspond to the specimens prepared with a 60% ceramic load. Degradation in SBF produces a porous nanostructure in the polymeric component indicating microdomains of different solubility and the formation of an apatite-like layer on the surface of the wollastonite component. All the compositions assayed present a biocompatibility at least of the level or even superior than the Thermanox® control used.

AEI/FEDER UE (DPI2017-90147-R).

In recent years, it has been verified that collective cell migration is a fundamental step in tumor spreading and metastatic processes. In this paper, we demonstrate for the first time how low-intensity ultrasound produces long-term inhibition of collective migration of epithelial cancer cells in wound healing processes. In particular, we show how pancreatic tumor cells, PANC-1, grown as monolayers in vitro respond to these waves at frequencies close to 1 MHz and low intensities (, Project PID2021-128985OB-I00 funded by MCIN/ AEI/10.13039/501100011033/“FEDER Una manera de hacer Europa and AEI, FEDER , UE DPI 2017-90147-R and Intramural call for new research projects for clinical researchers and emerging research groups IRYCIS (2018/0240).