Novel magnesium phosphate cements with high early strength and antibacterial properties

Magnesium phosphate cements (MPCs) have been extensively used as fast setting repair cements in civil engineering. They have properties that are also relevant to biomedical applications, such as fast setting, early strength acquisition and adhesive properties. However, there are some aspects that should be improved before they can be used in the human body, namely their highly exothermic setting reaction and the release of potentially harmful ammonia or ammonium ions. In this paper a new family of MPCs was explored as candidate biomaterials for hard tissue applications. The cements were prepared by mixing magnesium oxide (MgO) with either sodium dihydrogen phosphate (NaH(2)PO(4)) or ammonium dihydrogen phosphate (NH(4)H(2)PO(4)), or an equimolar mixture of both. The exothermia and setting kinetics of the new cement formulations were tailored to comply with clinical requirements by adjusting the granularity of the phosphate salt and by using sodium borate as a retardant. The ammonium-containing MPC resulted in struvite (MgNH(4)PO(4)·6H(2)O) as the major reaction product, whereas the MPC prepared with sodium dihydrogen phosphate resulted in an amorphous product. Unreacted magnesium oxide was found in all the formulations. The MPCs studied showed early compressive strengths substantially higher than that of apatitic calcium phosphate cements. The Na-containing MPCs were shown to have antibacterial activity against Streptococcus sanguinis, which was attributed to the alkaline pH developed during the setting reaction.     

Computed tomography and histological evaluation of xenogenic and biomimetic bone grafts in three-wall alveolar defects in minipigs

Objectives

This study aimed to compare the performance of a xenograft (XG) and a biomimetic synthetic graft (SG) in three-wall alveolar defects in minipigs by means of 3D computerised tomography and histology.

Materials and methods

Eight minipigs were used. A total of eight defects were created in the jaw of each animal, three of which were grafted with XGs, three with SGs, and two were left empty as a negative control. The allocation of the different grafts was randomised. Four animals were euthanised at 6 weeks and four at 12 weeks. The grafted volume was then measured by spiral computed tomography to assess volume preservation. Additionally, a histological analysis was performed in undecalcified samples by backscattered scanning electron microscopy and optical microscopy after Masson’s trichrome staining.

Results

A linear mixed-effects model was applied considering four fixed factors (bone graft type, regeneration time, anatomic position, and maxilla/mandible) and one random factor (animal). The SG exhibited significantly larger grafted volume (19%) than the XG. The anterior sites preserved better the grafted volume than the posterior ones. Finally, regeneration time had a positive effect on the grafted volume. Histological observations revealed excellent osseointegration and osteoconductive properties for both biomaterials. Some concavities found in the spheroidal morphologies of SGs were associated with osteoclastic resorption.

Conclusions

Both biomaterials met the requirements for bone grafting, i.e. biocompatibility, osseointegration, and osteoconduction. Granule morphology was identified as an important factor to ensure a good volume preservation.

Clinical relevance

Whereas both biomaterials showed excellent osteoconduction, SGs resulted in better volume preservation.

     

Effect of the particle size on the micro and nanostructural features of a calcium phosphate cement: a kinetic analysis

The aim of this work is to investigate the possibility of controlling the final micro and nanostructural features of a calcium phosphate cement by modifying the particle size of the starting powder, and to study the effect of this parameter on the kinetics of the setting reaction. The development of calcium phosphate materials with tailored structures at the micro and nanoscale levels could allow the modulation of some specific responses in biologic phenomena such as protein adsorption and cell adhesion, which strongly depend on the nano-sized roughness of the interface. It is shown that the higher specific surface, produced by the reduction of the particle size of the powder, strongly accelerates the hydrolysis of the alpha-TCP into calcium-deficient hydroxyapatite. The higher degree of supersaturation attained in the solution favours the nucleation of smaller crystals. Thus, by increasing the specific surface of the starting powder in a factor of 5, the size of the precipitated crystals is strongly reduced, and the specific surface of the set cement increases by a factor of 2. The reduction of the particle size produces a substantial decrease of the setting time and accelerates the hardening of the cement without significantly affecting the final strength attained. The mechanical strength achieved by the cement cannot be univocally related to the degree of reaction, without considering the microstructural features.     

Wet or dry mechanochemical synthesis of calcium phosphates? Influence of the water content on DCPD-CaO reaction kinetics

Mechanosynthesis of calcium phosphates can be performed under wet or dry conditions. In most papers and patents, grinding under wet conditions was selected. So far, only a few papers were devoted to dry mechanosynthesis of calcium phosphates. To understand why wet mechanosynthesis was preferred, the influence of water addition on the kinetics of the mechanochemical reaction of dicalcium phosphate dihydrate with calcium oxide was investigated. The DCPD disappearance rate constant k and the final reaction time t(f) were determined in each case and correlated with the water content present in the slurry. Results showed that the addition water (i) slowed down the reaction rate and (ii) increased the powder contamination by mill material (hard porcelain) due to ball and vial erosion; and that (iii) wet milling did not generate the expected products, in contrast to dry grinding, because porcelain induced hydroxyapatite decomposition with the formation of beta-tricalcium phosphate and silicon-stabilized tricalcium phosphate. Consequently, dry mechanosynthesis appears preferable to wet milling in the preparation of calcium phosphates of biological interest.     

Factors affecting the structure and properties of an injectable self-setting calcium phosphate foam

One of the main challenges in the investigation on calcium phosphate cements (CPC) lies in the introduction of macroporosity, without loosing the self-setting ability and injectability, characteristic of the cement-type materials. The benefits of macroporosity are related to the enhancement of bone regeneration mechanisms, such as angiogenesis and tissue ingrowth. In this work, the feasibility to obtain self-setting injectable macroporous hydroxyapatite foams by the incorporation of a protein-based foaming agent to a CPC is demonstrated. Albumen is combined with an alpha-tricalcium phosphate [Ca3(PO4)2, alpha-TCP] paste, which hydrolyzes to a calcium deficient hydroxyapatite during the setting reaction. A systematic study is presented, where the effect of different processing parameters is analyzed in terms of porosity, setting properties, injectability, and compressive strength. Self-setting foams with porosities up to 70%, which maintain their porous structure after injection, are obtained. These injectable foams can be used both for direct in vivo applications and for the fabrication of low temperature tissue engineering scaffolds.     

Immunogenicity of a new Salmonella Typhi Vi polysaccharide vaccine--vax-TyVi--in Cuban school children and teenagers

A randomized, controlled, double blind study was carried out in Cuban children and teenagers aged 9-13 years to evaluate the immunogenicity of vax-TyVi-Salmonella Typhi Vi polysaccharide vaccine-with respect control vaccines. Serum samples were taken before and 21 days after the immunization, and ELISA was used for the determination of antibodies to Vi polysaccharide. Subjects who received vax-TyVi and TYPHIM Vi (Pasteur-Mérieux) showed seroconversion rates of 85.61 and 78.36%, respectively. The geometric mean titer (GMT) values for Vi antibodies induced after vaccination were 6.27 microg/ml (5.40-7.38 microg/ml) and 5.97 microg/ml (5.01-7.10 microg/ml), respectively. In contrast, subjects receiving the tetanus toxoid vaccine showed 0% seroconversion.     

Biomechanical evaluation of fixation of clavicular fractures

Reproducible fractures of the midshaft of the clavicle were created in 14 fresh frozen human cadaveric clavicles. Under the three-point bending loading by a materials testing machine, the load to failure of fixation of the clavicular fractures treated with steel reconstruction plates (five specimens) and Herbert cannulated bone screw (nine specimens), was compared with a group control formed by five specimens of clavicles without osteosynthesis material. No statistically significant differences were observed between the three groups. In consequence and in terms of biomechanics, in clavicular acute fractures, both plating and intramedullary Herbert cannulated bone screw may be utilized in the treatment of these lesions.     

Effect of porosity and environment on the mechanical behavior of acrylic bone cement modified with acrylonitrile-butadiene-styrene particles: I. Fracture toughness.

The elastomeric copolymer acrylonitrile-butadiene-styrene (ABS) was added to a conventional acrylic bone cement matrix. The results obtained show that although strength and stiffness decreased with an increasing second phase volume fraction, ductility and toughness both increased. The crack propagation became stable for specimens containing over a 5% volume fraction of the second phase. The fracture toughness increased up to 60% when the amount of ABS reached 20% (v/v). For larger amounts linear elastic fracture mechanics techniques could not be used properly. The effects of porosity and environmental conditions on the mechanical behavior were also studied. The mechanisms that control the fracture process were investigated by means of scanning electron microscopy.     

Calcium phosphate cements as drug delivery materials

Calcium phosphate cements are used as synthetic bone grafts, with several advantages, such as their osteoconductivity and injectability. Moreover, their low-temperature setting reaction and intrinsic porosity allow for the incorporation of drugs and active principles in the material. It is the aim of the present work to: a) provide an overview of the different approaches taken in the application of calcium phosphate cements for drug delivery in the skeletal system, and b) identify the most significant achievements. The drugs or active principles associated to calcium phosphate cements are classified in three groups, i) low molecular weight drugs; ii) high molecular weight biomolecules; and iii) ions.     

Radiopaque acrylic cements prepared with a new acrylic derivative of iodo-quinoline.

A novel iodine-containing methacrylate, 2,5-diiodo-8-quinolyl methacrylate, has been synthesized and used in the preparation of acrylic radiopaque cements. The effect of incorporation of this monomer to the self-curing resins, on the curing parameters, swelling behaviour and mechanical properties was studied. The incorporation of the radiopaque compound 2,5-diiodo-8-hydroxyquinoline to the solid phase was also carried out for comparative experiments. A decrease in the peak temperature and an increase in the setting time was observed with the addition of the radiopaque monomer, however, the curing parameters did not appreciably change with the addition of the radiopaque compound to the solid phase. Swelling of the modified cements was in the same range as that of the radiolucent cement; however, the diffusion coefficients calculated according to the Fick's law were higher for the iodine-containing materials. The addition of 5 wt% of the iodine-containing methacrylate provided a significant increase in the tensile properties with respect to either control radiolucent formulations or BaSO4-containing formulations. Biocompatibility of the modified cements was studied by implantation of rods of the cements into rats and histological analysis of the surrounding tissue.