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Mechanical properties and radiopacity of experimental glass-silica-metal hybrid composites.

OBJECTIVES: Experimental glass-silica-metal hybrid composites (polycomposites) were developed and tested mechanically and radiographically in this fundamental pilot study. To determine whether mechanical properties of a glass-silica filled two-paste dental composite based on a Bis-GMA/polyglycol dimethacrylate blend could be improved through the incorporation of titanium (Ti) particles (particle size ranging from 1 to 3 microm) or silver-tin-copper (Ag-Sn-Cu) particles (particle size ranging from 1 to 50 microm) we measured the diametral tensile strength, fracture toughness and radiopacity of five composites. METHODS: The five materials were: I, the original unmodified composite (control group); II, as group I but containing 5% (wt/wt) of Ti particles; III, as group II but with Ti particles treated with 4-methacryloyloxyethyl trimellitate anhydride (4-META) to promote Ti-resin bonding; IV, as group I but containing 5% (wt/wt) of Ag-Sn-Cu particles; and V, as group IV but with the metal particles treated with 4-META. Ten specimens of each group were tested in a standard diametral tensile strength test and a fracture toughness test using a single-edge notched sample design and five specimens of each group were tested using a radiopacity test. RESULTS: The diametral tensile strength increased statistically significantly after incorporation of Ti treated with 4-META, as tested by ANOVA (P=0.004) and Fisher's LSD test. A statistically significant increase of fracture toughness was observed between the control group and groups II, III and V as tested by ANOVA (P=0.003) and Fisher's LSD test. All other groups showed no statistically significant increase in diametral tensile strength and fracture toughness respectively when compared to their control groups. No statistically significant increase in radiopacity was found between the control group and the Ti filled composite, whereas a statistically significant increase in radiopacity was found between the control group and the Ag-Sn-Cu filled composite as tested by ANOVA (P=0.000) and Fisher's LSD procedure. SIGNIFICANCE: The introduction of titanium and silver-tin-copper fillers has potential as added components in composites to provide increased mechanical strength and radiopacity, for example for use in core materials.

Algorithms↗

Controlled release of biomolecules from pH-sensitive network polymers prepared by radiation polymerization.

Copolymers of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) based hydrogels containing 5 and 10% of a cross-linking agent were studied as drug delivery systems. Terephthalic acid was covalently linked with HEMA, abbreviated as CA. Radiation copolymerization of HEMA and MAA, mixed with a particulate glibenclamide with the various ratios CA as crosslinking agent were carried out at the room temperature. The structure of the CA was confirmed by FTIR, H NMR and C NMR spectroscopy. The compositions of the cross-linked three-dimensional polymers were determined by FTIR spectroscopy. Glass transition temperature (T) of the network polymers was determined calorimetrically. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing an aqueous buffer solution (pH 7.4 and pH 1) at 37 degree C. The drug-release profiles indicate that amount drug release depends on their degree of swelling and cross-linking.

Calorimetry, Differential Scanning↗

The short-term blood biocompatibility of poly(hydroxyethyl methacrylate-co-methyl methacrylate) in an in vitro flow system measured by digital videomicroscopy.

An in vitro flow system for short-term blood biocompatibility testing of solution-castable polymeric biomaterials was developed. This system was relatively free of artefacts resulting from blood contact with materials other than the test material itself. In conjunction with epifluorescence videomicroscopy and digital image processing, this method provided a high resolution, quantitative, continuous analysis of platelet adhesion, aggregation, thrombus formation, and embolization on the biomaterial surface. This system was well suited for performing biochemical assays on post-contact blood for assessment of platelet activation and release as additional measures of the thrombogenicity of the test material. This method for biomaterials evaluation in vitro was demonstrated by a detailed examination of copolymers of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA). Videomicroscopic analysis of fluorescently labelled platelets adhering per unit area of the polymer surface after 5 min of flow at a wall shear rate of 500 s-1 showed a dramatic decrease with increasing HEMA fraction in the polymer. The release of serotonin and thromboxane A2 by platelets decreased with increasing HEMA fraction. Reflection interference contrast microscopy was used to examine focal contacts of platelets on the copolymer surfaces as a qualitative measure of the platelet-surface interaction. A polymer-dependent gradation in contact extent and morphology was observed, ranging from large contacts on P(MMA) to none on P(HEMA).

Biocompatible Materials↗

Complete spinal cord transection treated by implantation of a reinforced synthetic hydrogel channel results in syringomyelia and caudal migration of the rostral stump.

OBJECTIVE: Previously, we reported that synthetic poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) channels promoted regeneration of a small number of axons from brainstem motor nuclei yet provided limited functional recovery after complete spinal cord transection at T8 in rats. However, we found that these modulus channels partially collapsed over time. Therefore, we synthesized coil-reinforced PHEMA or PHEMA-MMA channels with greater elastic moduli and introduced a new spinal fixation technique to prevent collapse. We also assessed axonal regeneration within the new channels containing a cocktail of autologous peripheral nerve grafts, fibrin matrix, and acidic fibroblast growth factor. METHODS: After spinal cord transection, rats were divided into six groups: Groups 1 and 2 had either a PHEMA or PHEMA-MMA reinforced channel implanted between the stumps of the transected spinal cord with the cocktail; Groups 3 and 4 had either an unfilled reinforced PHEMA or PHEMA-MMA channel similarly implanted; Group 5 had an spinal cord transection without channel implanted, and Group 6 underwent the identical procedure to Group 1, but rats were sacrificed by 8 weeks for early histological assessment. Groups 1 to 5 were sacrificed at 18 weeks. RESULTS: There was no channel collapse at any time. However, there was no improvement in axonal regeneration or functional recovery among Groups 1 to 4 because of the unexpected development of syringomyelia and caudal migration of the rostral stump. Functional recovery was better in Groups 1 to 4 compared with Group 5 (P < 0.05). CONCLUSION: The use of channels to enhance regeneration of axons is promising; however, improvement of the design of the channels is required.

Animals↗

Light and electron microscopic observation of specific atrial granules using water-miscible resin as an embedding medium.

A mixture of glycol methacrylate (GMA) and Quetol 523 was examined as an embedding medium for atrial tissue to be selectively stained for specific atrial granules. Semi-thin sections of rat atrial tissue embedded in this resin were stained with lead hematoxylin and observed under a light microscope. Atrial granules were found to be specifically stained blue black with lead hematoxylin. The same semithin sections stained with OsO4 vapor were examined electron microscopically and the atrial granules could be distinguised clearly from other cytoplasmic components. The GMA-Quetol 523 mixture is a useful embedding medium for studying the distribution of specific atrial granules by light and electron microscopy.

Animals↗

Initiating polymerization of glycol methacrylate with cyclic diketo carbon acids.

Several pharmacologically active cyclic diketone carbon acids, including phenylbutazone and 2-phenyl-1,3-indandione, catalyze the polymerization of glycol methacrylate monomers. GMA-cyclic diketone carbon acid monomer mixtures incorporating imidazole polymerize smoothly without obvious exothermicity at temperatures ranging from ambient to -5 C without the use of ultraviolet light. The only equipment required for this embedding technique is a refrigerator with a freezing compartment which can maintain temperatures of -15 C. A recipe consisting of 5 ml glycol methacrylate (2-hydroxyethyl methacrylate), 0.8 ml 1-pentanol, 16 mg imidazole, and 30 mg monophenylbutazone is recommended for general use. The use of dicyclopentyl methacrylate-glycol methacrylate comonomer mixtures incorporating cyclic ketone catalysts is advocated, as blends of these monomers have low basophilia, and tissues embedded in these matrices stain sharply and brilliantly. It is hypothesized that the driving force for the cyclic ketone-mediated polymerization of glycol methacrylate under basic conditions is furnished by the lysis of cyclic ketone carbon acid peroxides.

Acrylates↗

Swelling of PHEMA based membranes in ethanol and their nitroglycerin permeabilities.

The aim of this study is to prepare PHEMA based polymeric membranes for a transdermal delivery system, which includes a skin permeation enhancer (i.e. ethanol) for nitroglycerin. Membranes were prepared by bulk polymerization of HEMA monomer. Polymerization was achieved in the presence of EGDMA, as the cross-linker, and AIBN as the initiator. MMA was used as a comonomer to improve the mechanical properties and to adjust the permeabilities of the resulting membranes. Water was also included in the polymerization mixture to control the matrix structure. Membranes with different chemical and physical structures were prepared. Swelling behaviour of these matrices in ethanol were observed. Nitroglycerin diffusion through swollen membranes (in ethanol) were investigated. It was obtained that the relative amounts of ingredients (i.e., HEMA, MMA, EGDMA and water) in the casting solutions affect both the equilibrium swelling values and the permeabilities. By increasing the water content and by decreasing the amounts of MMA and EGDMA both parameters can be increased. AIBN does not affect these parameters significantly.

Ethanol↗

Studies on radio-opaque polymeric biomaterials with potential applications to endovascular prostheses.

A new polymeric biomaterial, which uniquely combines radio-opacity (X-ray visibility) and low thrombogenicity, is described. First, preparation, purification, and identification of the essential monomeric building block, 2-[2'-iodobenzoyl]-ethyl methacrylate (3), are outlined. Second, [Figure: See text] the synthesis of the biomaterial, a terpolymer with composition MMA: HEMA: 3 = 65:15:20 (mole/mole/mole) is described. Third, the physico-chemical characteristics of the polymer (e.g. NMR spectroscopy, thermal behaviour) are given. Fourth, the in vitro thrombogenicity of the material was characterized by means of recent test assay. The combined results reveal that the terpolymer is very suitable for prosthetic applications in the cardiovascular system. A new prototype of an endovascular stent, made from the terpolymer, is presented. Stents find clinical use in interventional cardiology, in conjunction with percutaneous transluminal coronary angioplasty (PTCA). It is put forward that the stent prototype presented herein has, at least in principle, some advantages over existing (metallic) stents; these advantages are primarily owing to the unique combination of X-ray visibility and haemocompatibility which is presently achieved.

Biocompatible Materials↗

Preliminary study of hydrophilic hydrogel intraocular lens implants in cats.

Soft hydrophilic intraocular lenses (IOLs) made of an aminopolyamide (Duragel) and a hydroxyethylmethylmethacrylate (HEMA) hydrogel polymer were implanted in cats and followed for six weeks. During surgery, a 45-second purposeful contact between the lens surface and the corneal endothelium was made. During the course of the experiment, all implanted eyes maintained clear IOLs and manifested a continuing mild iritis. Scanning electron microscopy of the corneas revealed numerous microvilli but no damage to cell membranes. Scanning electron microscopy of the aminopolyamide IOLs revealed fibroblast growth on the surface. No fibroblast growth was noted on the surface of the HEMA IOLs. These experiments suggest that soft hydrogel IOLs may be better than conventional hydrophobic acrylic IOLs in minimizing endothelial contact damage. However, the observation of corneal microvilli may indicate a mild adverse reaction to the hydrogels, possibly from impurities. Fibroblast growth on the aminopolyamide may also be due to an ocular inflammatory response to the material or impurities. Hydrogel IOLs may be of interest because of their semirigid physical properties and greater safety on contacting the endothelium. However, considerable attention must be given to polymer composition and polymer purification.

Animals↗

Hemocompatibility of human whole blood on polymers with a phospholipid polar group and its mechanism.

The hemocompatibility of a polymer containing a phospholipid polar group, poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate(BMA)), with human whole blood was evaluated. When human whole blood without an anticoagulant was contacted with polymers, the blood cell adhesion and aggregation on the polymer without the MPC moiety was extensive, and considerable fibrin deposition was observed. This phenomenon was suppressed with an increase in the polymer MPC composition. Thus, the MPC moiety in the copolymer plays an important role in the nonthrombogenic behavior of the copolymer. These results were also confirmed by the whole blood coagulation time on the polymer surface which was determined by Lee-White method. The adsorption of phospholipids and proteins from human plasma on poly(MPC-co-BMA) was investigated to clarify the mechanism of the nonthrombogenicity observed with the polymer. The amount of phospholipids was increased; whereas, adsorbed proteins were decreased with an increase in the MPC composition. From these results, we concluded that the phospholipids adsorbed on poly(MPC-co-BMA) play the most important role in the nonthrombogenicity of the MPC copolymer.

Adsorption↗

Morphological and topographic effects on calcification tendency of pHEMA hydrogels.

Poly(2-hydroxyethyl methacrylate) hydrogels were prepared in the presence of varying concentrations of water, or a co-monomer ethoxyethyl methacrylate at different strengths of crosslinking agent ethylene glycol dimethacrylate. Calcification tendency and its correlation with monomer mixture composition, topography and porosity of these materials were investigated. Scanning (SEM) and transmission electron microscopy (TEM) was used to study topography and porosity respectively. Calcification and calcium diffusion ability in to the hydrogels were investigated by light microscopy, SEM and energy dispersive analysis of X-rays (EDAX) after incubation of the materials in a metastable calcifying solution for 48 days. Polymer and solvent volume fractions were also studied to determine if a correlation existed between porosity and calcification. Most of the series of hydrogels showed surface irregularities. Internal structure showed evidence of a porous structure in one of the series. Calcification studies indicated diffusion of calcium ions in some of the series. The diffusion of calcium is limited to 30-40 microm in most calcified specimens. For hydrogels that exhibited substantial surface irregularities and micro channels, the infiltration of calcium up to 200 microm was observed. Attempts to detect porosity by electron microscopy failed in some of the hydrogels due to difficulty in sample processing and sectioning. However, collaboration of the results with different techniques used, indicated that surface defects are the major contributors to calcium deposition. Decrease in porosity reduces the amount of calcium deposits and infiltration with decreasing solvent volume fraction which is associated with crosslinking concentration and initial water content of the polymer.

Biocompatible Materials↗

Studies on blood compatibility of terpolymers composed of methyl methacrylate, methoxypolyethyleneglycol methacrylate, and dimethylsiloxane methacrylate.

Terpolymers composed of methyl methacrylate (MMA), polydimethylsiloxane methacrylate (PDMSMA), and methoxypolyethyleneglycol methacrylate (MPEGMA), having different compositions were synthesized. Platelets were not adsorbed onto terpolymer surfaces composed of 50 wt% MMA, 25 wt% PDMSMA and 25 wt% MPEGMA, while on terpolymers with the other compositions, platelet adsorption and fibrin clot were observed. It was shown that PDMS segment was predominant on these terpolymer surfaces via XPS. Receding contact angles of terpolymers, on which no platelet was observed, showed intermediate values between PDMS- and MPEG-rich surfaces. It was suggested that these terpolymers had blood compatibility.

Adult↗

Application of new coatings for vascular grafts based on polyacrylic systems with antiaggregating activity.

A study has been made of the behaviour of knitted and woven Dacron mesh used in the preparation of vascular grafts when coated with either a layer of poly(2-hydroxyethyl methacrylate) or co-polymers of 2-hydroxyethyl methacrylate with 5, 10 or 20 wt% of an acrylic derivative of salicylic acid, 2-methacryloyloxybenzoic acid. In vitro studies were carried out to quantify the loss of polymer under flow conditions, and ex vivo studies were done in dogs to quantify the deposition of 111In-oxine-labelled platelets. The treated materials showed a lesser deposition of platelet thrombi when compared with the control group.

Animals↗

Poly(2-hydroxyethyl methacrylate)-based slabs as a mouse embryonic stem cell support.

Poly(2-hydroxyethyl methacrylate) (PHEMA) crosslinked with ethylene dimethacrylate (EDMA) or N,O-dimethacryloylhydroxylamine (DMHA) was obtained in the form of slabs by bulk radical polymerization. Two porosity-inducing methods were investigated, phase separation using a low-molecular-weight porogen and a salt-leaching technique using NaCl and saccharose. Compared with the phase separation, the salt-leaching created open porous structures with voids of the size and shape of crystallites. To address its potentials in the context of stem cell therapies, undifferentiated mouse embryonic stem cells D3 (ES D3 cells) were seeded on the slabs and analyzed for the ability to grow on different types of non-degradable and/or degradable porous PHEMA hydrogels. The cells were able to proliferate only on PHEMA crosslinked with EDMA or 2 wt% DMHA. In order to assess the effect of gelatin, which is routinely used for ES cell cultures, PHEMA slabs were soaked in gelatin solutions and compared the number of cells on gelatin-treated and untreated slabs 4 days after cell seeding. Surprisingly, the number of cells was only slightly higher on gelatin-treated slabs.

Animals↗

Oriented immobilization of galactose oxidase to bead and magnetic bead cellulose and poly(HEMA-co-EDMA) and magnetic poly(HEMA-co-EDMA) microspheres.

In order to obtain an active and stable oxidation reactor for daily use in biochemical laboratory we decided to immobilize galactose oxidase orientedly through a carbohydrate chain to the magnetic carriers. We used hydrazide derivatives of non-magnetic and magnetic bead cellulose and of magnetic and non-magnetic poly(HEMA-co-EDMA) microspheres. Activation of the enzyme molecules was done by sodium periodate in the presence of supplements (fucose, CuSO4, catalase). Orientedly immobilized galactose oxidase presents high storage stability and lower susceptibility to inappropriate microenvironmental conditions. Reactor reactivated by three pulses of D-galactose retained practically 100% of its native activity after 6 months. The positive properties of both magnetic carriers were entirely confirmed.

Animals↗

Preliminary in vitro cytotoxicity screening of a bead-formed macroporous hydrophilic polymer matrix.

A prescreen of the in vitro cytotoxicity of both the primary fabrication components and potential leachables from a bead-formed macroporous poly(2-hydroxyethyl methacrylate), (pHEMA) matrix has been carried out using INVITTOX Neutral red and Kenacid blue R dye binding methods. Of the eluants obtained from 24, 48, and 72-h incubated beads, only the 72-h eluant produced a greater than 20% (ID20) inhibition of 3T3-L1 cell proliferation with values of 20.98 +/- 2.33% and 21.41 +/- 1.37% inhibition for the Neutral red and Kenacid blue R binding methods, respectively. ID50 values for the fabrication components obtained using the Kenacid blue R method were generally higher than those obtained by the Neutral red assay, although the ranking of the chemicals in terms of their relative cytotoxicities was identical by both methods, i.e. ethylene glycol dimethacrylate > uranyl nitrate > purified HEMA > n-hexane > ethylene glycol (mmol 1(-1)). Whilst extended washing of finished PHEMA beads in water will reduce their acute in vitro cytotoxicity, this will only be achieved with some loss of previously encapsulated water soluble macromolecules.

2,4-Dinitrophenol↗