M. Gurruchaga

Application of tertiary amines with reduced toxicity to the curing process of acrylic bone cements

4-Dimethylaminobenzyl alcohol (DMOH) and 4-dimethylaminobenzyl methacrylate (DMMO) were used as the activators in the benzoyl peroxide initiated redox polymerization for the preparation of acrylic bone cement based on poly(methylmethacrylate) beads of different particle size. The residual monomer content of the cured cements was about 2 wt %, independent of the redox system used in the polymerization, indicating that the activating effect of the tertiary aromatic amines DMOH or DMMO was sufficient to reach a polymerization conversion similar to that obtained with the benzoyl peroxide (BPO) N,N-dimethyl-4-toluidine (DMT) system. The BPO/DMOH and BPO/DMMO redox systems provided exotherms of decreasing peak temperature and increasing setting time, and the cured materials presented higher average molecular weight and similar glass transition temperatures in comparison with those obtained when DMT was used as the activator. In addition, these activators are three times less toxic than the classical DMT.

The influence of drying method on the physical properties of some graft copolymers for drug delivery systems

Abstract Graft copolymers of methyl methacrylate (MMA) on various natural substrates (carboxymethyl cellulose, hydroxypropyl cellulose, carboxymethyl starch and hydroxypropyl starch) were prepared in aqueous medium by the ceric ion initiator method. Products were dried in two differents ways: in ovens (O products) and by lyophilization (L products). The extent of graft copolymerization was measured in terms of grafting efficiency (GE), grafting (G), total conversion (CT) and crude grafting (CG). As would be expected, by both drying methods almost identical values of grafting yields were obtained. Using scanning electron microscopy (SEM) some morphological particle size differences between O and L products were observed. These differences lead to different physical properties (particle size, moisture uptake, density and swelling capacity) of O and L products.

Modified acrylic bone cement with high amounts of ethoxytriethyleneglycol methacrylate.

One cause of arthroplasty failure is the brittle mechanical behavior of bone cements. However, the improvement of cement formulations must also be accompanied by the maintenance of a wide variety of characteristics. New bone cements were obtained by the substitution of high percentages, up to 60% (v/v), of methyl methacrylate (MMA) by a higher molecular weight and more hydrophilic monomer, ethoxytriethyleneglycol methacrylate (TEG). The essential advantages of these materials were the decrease of maximum temperature together with a decrease in the residual monomer content with respect to conventional cement formulations. The water absorption process obeyed diffusion laws and the equilibrium water content increased by the introduction of higher percentages of the hydrophilic component. This characteristic had an appreciable effect on the viscoelastic behavior analyzed by DMTA. These modified bone cements had reduced polymerization shrinkage and similar levels of porosity. Tensile test revealed that the introduction of TEGMA gave rise to an important modification of the mechanical behavior, with a noticeable increase in the fracture strain. This fact was also confirmed by means of the analysis of the fracture surfaces by SEM.

Hydrogels based on graft copolymerization of HEMA/BMA mixtures onto soluble gelatin: swelling behaviour

Abstract Graft copolymerization of mixtures of 2-hydroxyethyl methacrylate (HEMA) with n-butyl methacrylate (BMA) onto soluble gelatin was attempted using ceric ammonium nitrate as initiator, with the aim of obtaining hydrogels based on two different components: a natural polymer and a synthetic polymer. Other hydrogels were formed by simultaneous graft copolymerization and crosslinking using ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. Per cent grafting (%G), per cent grafting efficiency (% GE ) and per cent total conversion (%C 1 ) were calculated for various feed compositions and for various EGDMA concentrations. Equilibrium water content of the hydrogels was investigated as a function of the hydrophilicity of the polymers and the degree of crosslinking agent, and the influence of pH on the swelling behaviour of the hydrogels was determined. It was observed that the equilibrium water content increased as the percentage of hydrophilic monomer in the copolymer increased, and the swelling values increased with pH changes from the acid to the alkaline range.

Influence of the modification of P/L ratio on a new formulation of acrylic bone cement

The use of smaller powder/liquid (P/L) ratio favours the handling and wetting of poly(methyl methacrylate) (PMMA) beads in bone cement formulations. In this paper a P/L ratio of 1.86 is tested to overcome adhesion problems found in hydroxypropyl methacrylate (HPMA) modified bone cements and the influence on bone cement characteristics was analysed. The reduction of the P/L ratio leads to higher temperature peaks and shorter setting times, whereas the residual monomer content increases slightly. Water uptake obeys the diffusion laws, and the introduction of a more hydrophilic monomer gives rise to an increase of this parameter, which does not present significant changes with modification of the P/L ratio. Polymerization shrinkage is slightly greater because of the introduction of higher proportions of monomer in the formulation. Mechanical properties are similar to those obtained with conventional P/L ratios. The analysis of scanning electron microscopy (SEM) reveals an improvement of the adhesion between phases with respect to P/L = 2 formulations.

New injectable and radiopaque antibiotic loaded acrylic bone cements.

The use of antibiotic loaded bone cements (ALBCs) has become a common clinical practice in the prevention and treatment of prosthesis-related infections. However, due to antibiotic resistance, there is a general interest in broadening the antibacterial spectrum of currently used drugs. The aim of this work is to formulate ALBCs for specific use in vertebroplasty and kyphoplasty, and to study the effect of the addition of ciprofloxacin alone and in combination with vancomycin on some properties of the cement. The cements were formulated using bismuth salicylate as the radiopacifier. The setting properties, residual monomer content, release of antibiotics, rheological behavior, injectability, and mechanical properties of these formulations were studied. They showed long setting times and low curing temperatures. From the release studies, antibacterial properties are assumed because the concentration of released antibiotic was higher than the minimum effective. Although the experimental cements had slightly reduced mechanical properties, the other alterations shown were negligible.

Injectable Acrylic Bone Cements for Vertebroplasty Based on a Radiopaque Hydroxyapatite. Bioactivity and Biocompatibility

Radiopaque bone cements have been formulated to provide injectable pastes with improved bioactivity to be applied in vertebroplasty and kyphoplasty techniques. The bioactive compound was strontium containing hydroxyapatite salt, which was introduced as obtained (SrHA) or after treatment with MMA monomer (SrHA-t). The in vitro bioactivity of the cements was tested in cement films or in cement pastes introduced directly in a simulated body fluid (SBF) solution at 37 degrees C to mimic the in vivo conditions. Precipitation of an apatite-like layer was observed for the 20 wt %-SrHA-t containing cement in the first experiments, and in all formulations in the second ones. The deposited particles were characterized by FTIR spectroscopy and by EDAX analysis. Radiopacity of cements after immersion in SBF was confirmed. The biocompatibility exhibited by the SrHA containing cements was, in some cases, superior to that shown by a formulation with 10 wt % of BaSO(4). The new formulations prepared with the treated filler exhibited the lowest cytotoxicity and enhanced cellular proliferation. The in vivo biocompatibility tested by an intramuscular model in rats indicated the formation of a membrane formed by collagen fibers containing fibroblasts with no inflammatory cells, such as macrophages, giant cells or lymphocytes in all formulations.

Characterization of new acrylic bone cement based on methyl methacrylate/1-hydroxypropyl methacrylate monomer.

New formulations of acrylic bone cement based on methyl methacrylate/1-hydroxypropyl methacrylate (MMA/HPMA) monomers were developed with the purpose of obtaining more ductile materials with reduced polymerization shrinkage. In this way, the ductility of such materials increased, but the introduction of high percentages of the hydrophilic component produced an important decrease in Youngs modulus and strength. To ascertain the reason for the deterioration of the tensile parameters, an analysis by scanning electron microscopy of these formulations was carried out; it revealed poor adhesion between the matrix and poly(MMA) beads. We also observed that the polymerization shrinkage increased as the amount of hydrophilic monomer in the formulation decreased, and the 50% (v/v) HPMA modified bone cement compensated for this volume reduction with its water uptake swelling. Measurements taken on the setting time and polymerization exotherm showed a decrease in the former and an increase in the latter, because of the introduction of a more reactive monomer in the bone cement formulation.

A pH-sensitive hydrogel based on poly(ethoxy triethylene glycol monomethacrylate)

Abstract Ethoxy triethylene glycol monomethacrylate was synthesized and polymerized at 80°C in dimethyl-formamide solution with AIBN as initiator. Both monomer and polymer were characterized by 13 C n.m.r. spectroscopy. The analysis of the microstructure of the poly(ethoxy triethylene glycol monomethacrylate), PTEG, revealed an isotacticity parameter of 0.24, rather similar to free-radical poly(methyl methacrylate) and other poly(alkyl methacrylate)s. Swelling behaviour of the polymer was studied by the immersion of films in water and in buffered solutions at various pH values from 1 to 10. The hydration process was followed gravimetrically and the diffusion of water was analysed on the basis of the stress relaxation model of polymer chains. The results obtained are in good agreement with a second-order diffusion kinetics. A sharp increase of the equilibrium hydration degree between pH 5.5 and 7.4 is observed. The pH-sensitive transition is reversible, as is shown by the dehydration of swollen gels when they are introduced into acidic solutions (pH 1–5) after swelling in alkaline media at pH 8–10.

Graft copolymerization of hydroxylic methacrylates and ethyl acrylate onto amylopectin

Abstract In order to achieve new biocompatible materials, graft copolymerization of mixtures of hydroxyethyl methacrylate/ethyl acrylate (HEMA/EA) and hydroxypropyl methacrylate/ethyl acrylate (HPMA/EA) onto amylopectin by ceric ammonium nitrate initiation was carried out. The influence of feed composition was studied with respect to the characteristic grafting reaction yields. Homopolymer formation decreases as the per cent of HEMA monomer increases in the feed and increases as the per cent of HPMA monomer increases in the feed. The values obtained for the percentage grafting were quite high for all the feed compositions.