Amisel Almirall

Foamed surfactant solution as a template for self-setting injectable hydroxyapatite scaffolds for bone regeneration.

The application of minimally invasive surgical techniques in the field of orthopaedic surgery has created a growing need for new injectable synthetic materials that can be used for bone grafting. In this work a novel fully synthetic injectable calcium phosphate foam was developed by mixing alpha-tricalcium phosphate (alpha-TCP) powder with a foamed polysorbate 80 solution. Polysorbate 80 is a non-ionic surfactant approved for parenteral applications. The foam was able to retain the porous structure after injection provided that the foamed paste was injected shortly after mixing (typically 2.5 min), and set through the hydrolysis of alpha-TCP to a calcium-deficient hydroxyapatite, thus producing a hydroxyapatite solid foam in situ. The effect of different processing parameters on the porosity, microstructure, injectability and mechanical properties of the hydroxyapatite foams was analysed, and the ability of the pre-set foam to support osteoblastic-like cell proliferation and differentiation was assessed. Interestingly, the concentration of surfactant needed to obtain the foams was lower than that considered safe in drug formulations for parenteral administration. The possibility of combining bioactivity, injectability, macroporosity and self-setting ability in a single fully synthetic material represents a step forward in the design of new materials for bone regeneration compatible with minimally invasive surgical techniques.

α-Tricalcium phosphate cements modified with β-dicalcium silicate and tricalcium aluminate: Physicochemical characterization, in vitro bioactivity and cytotoxicity

Biocompatibility, injectability and in situ self-setting are characteristics of calcium phosphate cements which make them promising materials for a wide range of clinical applications in traumatology and maxillo-facial surgery. One of the main disadvantages is their relatively low strength which restricts their use to nonload-bearing applications. α-Tricalcium phosphate (α-C3P) cement sets into calcium-deficient hydroxyapatite (CDHA), which is biocompatible and plays an essential role in the formation, growth and maintenance of tissue-biomaterial interface. β-Dicalcium silicate (β-C2S) and tricalcium aluminate (C3A) are Portland cement components, these compounds react with water to form hydrated phases that enhance mechanical strength of the end products. In this study, setting time, compressive strength (CS) and in vitro bioactivity and biocompatibility were evaluated to determine the influence of addition of β-C2S and C3A to α-C3P-based cement. X-ray diffraction and scanning electron microscopy were used to investigate phase composition and morphological changes in cement samples. Addition of C3A resulted in cements having suitable setting times, but low CS, only partial conversion into CDHA and cytotoxicity. However, addition of β-C2S delayed the setting times but promoted total conversion into CDHA by soaking in simulated body fluid and strengthened the set cement over the limit strength of cancellous bone. The best properties were obtained for cement added with 10 wt % of β-C2S, which showed in vitro bioactivity and cytocompatibility, making it a suitable candidate as bone substitute.

β-Dicalcium silicate-based cement: Synthesis, characterization and in vitro bioactivity and biocompatibility studies

β-dicalcium silicate (β-Ca₂ SiO₄, β-C₂ S) is one of the main constituents in Portland cement clinker and many refractory materials, itself is a hydraulic cement that reacts with water or aqueous solution at room/body temperature to form a hydrated phase (C-S-H), which provides mechanical strength to the end product. In the present investigation, β-C₂ S was synthesized by sol-gel process and it was used as powder to cement preparation, named CSiC. In vitro bioactivity and biocompatibility studies were assessed by soaking the cement samples in simulated body fluid solutions and human osteoblast cell cultures for various time periods, respectively. The results showed that the sol-gel process is an available synthesis method in order to obtain a pure powder of β-C₂ S at relatively low temperatures without chemical stabilizers. A bone-like apatite layer covered the material surface after soaking in SBF and its compressive strength (CSiC cement) was comparable with that of the human trabecular bone. The extracts of this cement were not cytotoxic and the cell growth and relative cell viability were comparable to negative control.

Injectability of a Macroporous Calcium Phosphate Cement

In this work an injectable and self setting calcium phosphate/albumen foam is developed. The effect of both the amount of albumen and the particle size of the starting a-tricalcium phosphate (a-TCP) powder on the injectability of the cement paste is studied. X-ray diffraction (XRD) and infrared (IR) analysis of the samples reveal that the hydrolysis of a-TCP to calcium deficient hydroxyapatite (CDHA) is not affected by the addition of albumen. A foamed structure formed by spherical pores with diameters between 100 and 500 µm is observed by SEM. This porous structure is maintained after injection of the paste, although some deformation of the pores is produced due to the extrusion process. The injectability of the cements is increased by the presence of albumen as compared with cements prepared in the same conditions but without foaming agent.

Effect of Albumen as Protein-Based Foaming Agent in a Calcium Phosphate Bone Cement

In this work, the preparation and characterization of a macroporous α-tricalcium phosphate ( α-TCP) cement with albumen as foaming agent is discussed. X-ray diffraction (XRD) and infrared (IR) analysis of the samples reveal that the convers ion of α-TCP to calcium deficient hydroxyapatite (CDHA) was not affected by the addition of albumen in the cement paste. SEM observations showed the formation of spherical macropores with diameter s b tween 100 and 500 μm. The use of phosphate solutions, which have an accelerating effect of the setting reaction, influenced the foam stability, reducing the macroporosity of the set cements.

Fabrication of Low Temperature Hydroxyapatite Foams

Bone tissue engineering requires appropriate scaffold materials with a highinterconnected macroporosity. In this work a novel two-step method, based in the foaming of a calcium phosphate cement paste by the addition of hydrogen peroxide, and its subsequent hy drolysis to a calcium deficient hydroxyapatite (CDHA) is presented. The s iz of the interconnected macropores ranged between 50 μm and 2 mm, reaching the total porosity a maximum value of 66 %. The foaming capacity of the H 2O2 solution was strongly influenced by the particle size of the αtricalcium phosphate ( α-TCP) powder. The size of the macropores increased with increasing L/P ratio. As expected, the compressive strength of the apatitic foams decreased with increasing porosity, ranging between 2 and 9 MPa. Introduction One of the most promising approaches to the problem of bone regeneration a nd rep ir is bone tissue engineering (BTE). To guide in vitro or in vivo tissue regeneration, it is necessary to obtain appropriate scaffold materials with a high-interconnected macroporosi ty. For this application, several porous ceramic manufacturing techniques have been proposed [1-3]. How ever, the majority of these methods are based on the production of high temperature apatites , which are known to be hardly resorbable in normal physiological conditions. In this work an alte rn tive route is proposed to develop macroporous calcium phosphate scaffolds at low temperature, fr om calcium phosphate cements. Consolidation is obtained not by sintering, but through a low temper ature setting reaction. This approach has several advantages: the cementing reaction takes place at low temperature and therefore the final product is a low temperature pr cipitated hydroxyapatite, chemically more similar to the biological apatites, and with a much higher specific surface than that of a sintered hydroxyapatite. All these factors contribute to bring this materia l a higher reactivity, as compared to a ceramic hydroxyapatite. In addition, the low temperature processing allows the introduction of drugs, proteins or signaling molecules into the material. Materials and Methods To prepare the foams, an α-TCP powder obtained by solid state reaction at 1400oC, which contained a 2 wt% PHA as a seed material [4], was mixed with a 10 vol% aqueous solutions of hydrogen peroxide (H2O2) as foaming agent. The parameters studied were: (i) The liquid to powder ratio of the mixture (L/P = 0.32 and 0.38 ml/g) and (ii) the particle size of the α-TCP powder: two powders were studied, a coarse powder (average size 5.6 μm) and a fine powder (average size 2.2 μm). In order to evaluate the efficiency of foaming process, materials w ith no hydrogen peroxide on the liquid phase were also prepared. The experimental design is shown in Table 1. Key Engineering Materials Online: 2003-12-15 ISSN: 1662-9795, Vols. 254-256, pp 1001-1004 doi:10.4028/www.scientific.net/KEM.254-256.1001

Sistemas de Liberación Controlada de Fármacos a Partir de Materiales para la Restauración del Tejido Óseo

Nowadays, two of the most important problems are the high incidence of bone infections and the inflammatory response of the human organism when an implant is used. For this reason, the inclusion of drugs in materials for bone restoration is an interesting and promising approach to solve this problem. On this paper, drug delivery systems from bone restoration materials making little modifications to classic materials such as calcium phosphate cements, PMMA acrylic cements and coating metals were prepared, characterized and evaluated. All the prepared matrixes showed no-interaction between main components of formulation allowing the composition to lead the behavior of drug profile. The modifications made to classic bone materials on hydrophilicity and porosity, two important characteristics, helped to improve the drug delivery capacity. The ending results of delivery moved between 40-95 % in different time ranges according to composition which allows different possible application of these materials.

Preparation and characterization of hydrophilic composites AA/EPMA loaded with hydroxyapatite.

Copolymeric composites of acrylamide (AA) and 2,3-epoxypropyl methacrylate (EPMA) with hydroxyapatite (HA) load were studied. Swelling studies reports an anomalous or non-Fickian behavior following a good fitting to a pseudo second order mathematical treatment (α = 0.05, p < 0.0001). The composites showed a strong dependence on pH, related with the variations in the swelling behavior. The addition of load induces a diminution of swelling capacity and an increase of diametric tensile strength (DTS) ranging between 20 and 90 kPa. The calorimetric experiments showed two steps at 78°C and 255°C assigned to water loss and samples Tg. The drug control released was adjusted to a two-term equation obtaining a diffusion coefficient around 10(-5) cm(2) /s. The samples showed a significant bioactivity in vitro and it was certified by SEM, EDS and surface area calculus.

Cementos Biomédicos de Fosfato Tricálcico Reforzados con Silicatos y Aluminatos de Calcio-Preparación, Caracterización y Estudios de biodegradación

The combination of in situ self-setting and biocompatibility makes calcium phosphate cements highly promising materials for a wide range of clinical applications. However, its low strength limits its use to only non-stress applications. α-Tricalcium phosphate (α-TCP) cement sets into calcium-deficient hydroxyapatite (CDHA), which is a biocompatible compound and can induce osteointegration. β-Dicalcium silicate (β-C2S) and tricalcium aluminate (C3A) are Portland cement components, these compounds react with water to form hydrated phases that enhance mechanical strength of the end products. In this investigation, were prepared α-TCP cements modified with β-C2S and C3A. α-TCP powder was prepared through acid-base method, β-C2S and C3A were synthesized by sol-gel method. Materials were characterized chemical and physically. Biodegradability was studied by soaking the materials in simulated body fluid (SBF) at 37°C for 7 days. All cements exhibited long setting times and excellent setting temperature. T (100% α-TCP) and TS10 (10%-β-C2S) were converted to CDHA after 7 days soaking in SBF and their compressive strength were comparable to that of trabecular bone. TA10 (10%-C3A) was only partly converted to CDHA and showed the lowest compressive strength.