No evidence for the growth-stimulating effect of monomers on cariogenic Streptococci.

BACKGROUND: In spite of contradicting results, the high susceptibility of composites for secondary caries is still often associated with the bacterial growth-stimulating effect of released methacrylate monomers. However, most studies that showed this effect were performed with techniques having inherent limitations (spectrophotometry). OBJECTIVES: Therefore, our objective was to determine the effect of four methacrylate monomers (2-Hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA), ethylene glycol dimethacrylate (EGDMA), diethylene glycol dimethacrylate (DEGDMA)) on the growth of two caries-associated bacteria, Streptococcus mutans and sobrinus, and one non-cariogenic species, Streptococcus sanguinis, using TaqMan quantitative polymerase chain reaction (qPCR) to quantify bacterial DNA. MATERIALS AND METHODS: Cultures were exposed to monomer solutions selected after spectrophotometric growth measurements. At baseline and predetermined time intervals, bacterial DNA was extracted and quantified with TaqMan qPCR. Biofilms grown in the presence of monomers were analyzed with scanning electron microscopy (SEM). RESULTS: Spectrophotometry indeed showed increased growth rates of all three strains with 5 mM TEGDMA, EGDMA, and DEGDMA and increased total biomass of S. sanguinis with 5 mM TEGDMA. However, qPCR failed to show any growth-stimulating effect of these monomers on S. mutans and S. sobrinus. In contrast, some monomers exhibited a growth-inhibiting effect on S. sanguinis. SEM revealed extracellular matter in S. sobrinus and S. sanguinis biofilms, which might be attributed to polymer formation. CONCLUSIONS: Techniques which quantify bacterial DNA are more appropriate to evaluate bacterial growth in the presence of monomers than spectrophotometry. CLINICAL RELEVANCE: Even though methacrylate monomers did not affect the growth of cariogenic species, growth inhibition of S. sanguinis, a non-cariogenic antagonistic species, may lead to ecological shifts towards higher cariogenicity.

Biocompatibility of 4-META/MMA-TBB resin used as a dental luting agent.

STATEMENT OF PROBLEM: The bonding and biological properties of currently used luting/cementing materials need to be improved. 4-Acryloyloxyethyl trimellitate anhydride/methyl methacrylate-tri-n-butylborane (4-META/MMA-TBB) resin is primarily used for splinting mobile teeth or treating fractured teeth. It undergoes moisture-resistant polymerization and bonds strongly to dentin and metals. PURPOSE: The purpose of this in vitro study was to compare the biological and biochemical properties META/MMA-TBB resin with those of conventional polymethyl methacrylate (PMMA)-MMA resin and other currently used luting materials in order to determine whether it may be a viable dental luting agent. MATERIAL AND METHODS: The degree of polymerization of 4-META/MMA-TBB resin, PMMA-MMA autopolymerizing resin, 10-methacryloyloxydecyl dihydrogen phosphate-dimethacrylate (MDP-DMA) adhesive resin, and a glass ionomer cement was measured by Fourier-transformed infrared spectroscopy. Free radical production during setting was evaluated by electron spin resonance (ESR) spectroscopy. Rat dental pulp cells cultured on these materials were examined for cell viability, attachment, proliferation, and functional phenotype. RESULTS: The degree of polymerization of 4-META/MMA-TBB resin was 82% thirty minutes after preparation, compared to 66% for PMMA-MMA autopolymerizing resin. ESR spectroscopy revealed free radical production from 4-META/MMA-TBB resin and glass ionomer cement was equivalent 24 hours after preparation, with no spike in radical generation observed. In contrast, free radical production from PMMA-MMA and MDP-DMA adhesive resins was rapid and sustained and 10 to 20 times greater than that from 4-META/MMA-TBB. The percentage of viable dental pulp cells 24 hours after seeding was considerably higher on MDP-DMA and 4-META/MMA-TBB resin than on glass ionomer cement. Cell number, proliferation, and alkaline phosphatase activity were highest on 4-META/MMA-TBB resin and lowest on the glass ionomer cement. CONCLUSIONS: 4-META/MMA-TBB resin is at least as biocompatible, and perhaps even more biocompatible, than other current luting materials, with fast, favorable, and nontoxic polymerization properties. Further in vivo and human studies of 4-META/MMA-TBB resin as a dental luting agent are warranted.

Effect of dentin desensitizing procedures on methyl methacrylate diffusion through dentin.

BACKGROUND: Acrylic and bisacryl resins are widely used both during the temporization phase as well as for provisional restorations and the effect of external agents on dentin sensitivity can be reduced by the obliteration of the tubules. OBJECTIVE: The purpose of this study was to evaluate diffusion of methyl methacrylate monomer through dentin by high performance liquid chromatography (HPLC) after three different desensitizing procedures during the fabrication of two different provisional crown materials. MATERIALS AND METHODS: Forty extracted restoration and caries free human premolar teeth were used in this study. Thermoplastic vacuum formed material was used as a matrix to fabricate provisional restorations for each tooth before crown preparation. Teeth were prepared for a metal supported ceramic crown with 1 mm shoulder margins and then crown parts were separated from cementoenamel junction with a carborundum disk perpendicular to the long axis of the teeth. To the cementoenamel junction of each tooth a polypropylene chamber was attached that contains 1.5 cm 3 of deionized distilled water. Prepared teeth were divided into four groups ( n = 10) including control, desensitizing agent (DA) application, neodymium-doped yttrium aluminum garnet (Nd: YAG) laser irradiation (LI), and LI after DA application groups. After application of DA (except control) each group were divided into two subgroups for fabrication of provisional restorations ( n = 5). Two autopolymerizing provisional materials (Imident (Imicryl) and Systemp C and B (Ivoclar, vivadent)) were used to fabricate provisional restorations using the strips. Water elutes were analyzed by HPLC at 10 min and 24 h. RESULTS: The monomer diffusion values varied statistically according to desensitizing procedures, provisional resin systems, and the time periods. Monomer diffusion through dentin surfaces desensitized with Nd: YAG LI after DA application was the lowest. CONCLUSIONS: Nd: YAG LI in association with DA application is an effective combination to eliminate monomer diffusion through dentin to pulpal chamber.

The effect of adding tobramycin to Simplex P cement on femoral stem micromotion as measured by radiostereometric analysis: a 2-year randomized controlled trial.

BACKGROUND: Previous in vitro research on addition of antibiotics to bone cement has found no statistically significant deterioration in mechanical properties. However, no clinical studies have compared the performance of tobramycin-laden bone cement with that of standard bone cement (Simplex P). PATIENTS AND METHODS: 23 patients (25 hips) were randomized to receive an Exeter (Stryker Orthopaedics) femoral stem cemented with either Simplex P (standard) or Simplex T (tobramycin-laden) cement. There were 2 years of follow-up, with scheduled radiostereometric (RSA) examinations. RESULTS: All stems migrated distally and showed some degree of retroversion. No clinically significant differences in stem subsidence or retroversion were found between the Simplex T and Simplex P cement groups after 2 years. Overall subsidence was less than in previous studies, probably due to a postponed initial post-surgical examination. Rates of subsidence in both cement groups were consistent with those from previous studies of Exeter stems. INTERPRETATION: Subsidence of the femoral stem after 2 years was similar in the Simplex T (tobramycin-laden) and Simplex P (standard) groups.

Intercalary segmental reconstruction of long bones after malignant bone tumor resection using primary methyl methacrylate cement spacer interposition and secondary bone grafting: the induced membrane technique.

BACKGROUND: Bone reconstruction after surgical resection of malignant bone tumor in children remains a difficult challenge and various techniques exist. Induced membrane reconstruction as described by Masquelet et al has been reported in traumatic large bone defects. We have been using this 2-stage technique after primary malignant bone tumors resection in children since 2000. METHODS: We retrospectively studied 12 cases: 6 Ewing sarcomas and 6 osteosarcomas. Mean age of the patients was 9 years old (range, 3 to 15.5 y). Surgical treatment consisted of wide resection and insertion of a cement spacer then secondary bone grafting. All patients had neoadjuvant and adjuvant chemotherapy and 2 patients had adjuvant radiotherapy. RESULTS: Surgical excision was complete in all cases. There was no local recurrence at 6.2 years (range, 4.6 to 9.1 y) follow-up. Three patients had pulmonary metastasis (of whom 1 deceased) and 1 had a metastasis on the contralateral limb. The 11 patients operated on the lower limb achieved weight bearing 4.1 months (range, 0.2 to 14.2 mo) after the second stage of the procedure. Complications were numerous with 7 nonunions (4 unifocal and 3 bifocal), 5 fractures (in 4 patients), 5 protruding wires (in 4 patients), and 2 femoral varus deformities. There was no infection. CONCLUSIONS: Induced membrane reconstruction seems to be a simple and reliable technique in pediatric bone tumors and these results are promising. Extended use of locking nails could reduce the high rate of nonunion though it is not always possible in skeletally immature patients. LEVEL OF EVIDENCE: IV (case series).

Percutaneous osteoplasty with a bone marrow nail for fractures of long bones: experimental study.

PURPOSE: To develop percutaneous osteoplasty with the use of a bone marrow nail for fixation of long-bone fractures, and to evaluate its feasibility and safety in vivo and in vitro. MATERIALS AND METHODS: Six long bones in three healthy swine were used in the in vivo study. Acrylic cement was injected through an 11-gauge bone biopsy needle and a catheter into a covered metallic stent placed within the long bone, creating a bone marrow nail. In the in vitro study, we determined the bending, tug, and compression strengths of the acrylic cement nails 9 cm long and 8 mm in diameter (N = 10). The bending strength of the artificially fractured bones (N = 6) restored with the bone marrow nail and cement augmentation was then compared with that of normal long bones (N = 6). RESULTS: Percutaneous osteoplasty with a bone marrow nail was successfully achieved within 1 hour for all swine. After osteoplasty, all swine regained the ability to run until they were euthanized. Blood tests and pathologic findings showed no adverse effects. The mean bending, tug, and compression strengths of the nail were 91.4 N/mm(2) (range, 75.0-114.1 N/mm(2)), 20.9 N/mm(2) (range, 6.6-30.4 N/mm(2)), and 103.0 N/mm(2) (range, 96.3-110.0 N/mm(2)), respectively. The bending strength ratio of artificially fractured bones restored with bone marrow nail and cement augmentation to normal long bone was 0.32. CONCLUSIONS: Percutaneous osteoplasty with use of a bone marrow nail and cement augmentation appears to have potential in treating fractures of non-weight-bearing long bones.

The compressive properties of bone cements containing large doses of antibiotics.

The addition of large amounts of antibiotics to bone cement provides a convenient local delivery, but may influence the compressive properties of the cement. Flucloxacillin and vancomycin were added to Simplex P (Stryker, Limerick, Ireland) and VersaBond (Smith & Nephew) cements. Tripling the antibiotic dose from 2 to 6 g had little effect on the static compressive properties 24 hours after curing. After 4 weeks in phosphate-buffered saline, there was marked decrease in properties with the addition of antibiotics. Compressive strength of cements with 6 g of antibiotic was reduced to near or below the ASTM and ISO minimum of 70 MPa after 4 weeks in phosphate-buffered saline. Microcomputer tomography revealed increased porosity and clumping of the radiopacifier with the addition of antibiotics.

Effect of acute methyl methacrylate vapor inhalation on smokers' and non-smokers' respiratory function in a sample of male dentistry students.

BACKGROUND: Methyl methacrylate (MMA) is one of the widely used organic monomers in dentistry. It may cause multiple adverse reactions, ranging from allergic reaction to systemic toxicity. Dentistry students are exposed to MMA in an acute manner; however, the concentration of its vapor cannot be estimated well. OBJECTIVES: The aim of this study was to evaluate the effect of acute MMA vapor inhalation on the pulmonary function of dental students, both smokers and non-smokers. MATERIAL AND METHODS: Thirty-eight male dental students were divided into 2 groups (group 1 - smokers and group 2 - non-smokers). The lung function parameters of the students were tested with a spirometer during their ordinary training work in a prosthodontics laboratory, before contact with MMA and immediately after it. The lung function test was performed using a standard protocol. The students were asked not to use any perfume or aromatic overlaps for a period of 24 h before starting the tests. RESULTS: The researchers noted a statistically significant decrease (p ≤ 0.05) in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75), and forced expiratory flow at 25% (FEF25) and 50% (FEF50) of the pulmonary volume in smokers and non-smokers by comparing the preand post-work tests. CONCLUSIONS: Acute inhalation of MMA vapor induced a moderate restriction of pulmonary function in dental students, both smokers and non-smokers, during their routine prosthodontics laboratory training work. No differences in the results of the pulmonary function tests between smokers and non-smokers were observed.

Methyl methacrylate modified chitosan: Synthesis, characterization and application in drug and gene delivery.

A methyl methacrylate (MMA) modified chitosan (CS) conjugate (CSMMA) has been synthesized by a green method via Michael addition reaction between CS and MMA in ethanol. The synthesized conjugate was characterized by FT-IR, 1H NMR, X-ray diffraction spectrometry and SEM analysis. The results confirmed that CS was covalently linked to MMA yielding a highly porous framework. The uses of CSMMA were analyzed as a potential gene and drug delivery agent. CSMMA proved to be a reasonably good gene delivery agent based on transfection efficiency studies in mammalian cancer cell lines (A549, HeLa and HepG2). For drug delivery studies, nanoparticles of the CSMMA biopolymer were prepared by ionic gelation method with sodium tripolyphosphate (TPP). The prepared nanoparticles were characterized in terms of FE-SEM, DLS and zeta potential. In vitro drug release study of curcumin loaded CSMMA nanoparticles showed its maximal entrapment efficiency up to 68% and the drug release was more rapid at a pH (5.0) lower than physiological pH.

Response of the bivalve Unio tumidus and freshwater communities in artificial streams for hazard assessment of methyl methacrylate.

In artificial streams (pilot rivers) supplied with the river water of Gave de Pau (France), we studied the effects of methyl methacrylate (MMA) on the autochthonous bivalve Unio tumidus transferred into the streams and on natural freshwater communities colonizing the channels. Unio tumidus and freshwater communities were exposed to MMA for 15 and 30 d, respectively, at measured concentrations ranging from 0.6 to 122 mg/L. Biomarkers studied in the digestive gland and gills of U. tumidus comprised detoxication systems (namely, antioxidant enzyme activities and glutathione status) and lipid peroxidation as a marker of cytotoxicity. Biocoenotic indicators were used to evaluate effects on benthic invertebrates and diatoms. In bivalves, a decrease in antioxidant levels was found at the lowest concentrations tested (0.6 and 6 mg/L), whereas an increase in lipid peroxidation and mortality was registered at 30 mg/L after 15 d of exposure. Disturbances in freshwater communities occurred after 30 d at MMA concentrations of greater than 30 mg/L. Antioxidant responses in bivalves were recorded at the lowest MMA concentration tested, which was close to the predicted no-effect concentration (0.74 mg/L), and cytotoxicity was registered at a concentration corresponding to the 21-d no-observed-effect concentration for Daphnia magna. On the basis of the criteria studied, antioxidant biomarkers of bivalves appeared to be more sensitive than biocoenotic indicators to MMA.

mRNA-induction and cytokine release during in vitro exposure of human nasal respiratory epithelia to methyl methacrylate.

BACKGROUND: Methyl methacrylate (MMA) has been reported to cause histopathological changes in rodent nasal epithelium after inhalation challenges. Data in humans are lacking. METHODS: In this in vitro design 22 primary cell cultures taken from inferior turbinate tissue of healthy individuals were exposed to MMA concentrations of 50 ppm (German MAK-value) and 200 ppm. mRNA expression and cytokine release of inflammatory mediators were quantified after 4h and after 24h. Controls were exposed to synthetic air. Q-PCR analysis was performed for TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2. ELISA assays were performed from culture supernatants for TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1 and GMCSF. RESULTS: Acute inductions of mRNA after 4h were observed for TNF-alpha, IL-1beta, IL-6, IL-8 and MCP-1 at 50 ppm. ELISA analysis of the described parameters did not reveal any significant upregulations at both concentrations after both 4h and 24h. CONCLUSIONS: The obtained data suggest that exposure of human respiratory epithelia in vitro to 50 ppm and to 200 ppm of MMA does not induce lasting upregulation of the inflammatory mediators measured in this study. The exposure limit of 50 ppm appears safe following these results obtained from human respiratory epithelia.

Radical-scavenging activity of natural methoxyphenols vs. synthetic ones using the induction period method.

The radical-scavenging activities of the synthetic antioxidants 2-allyl-4-X-phenol (X = NO2, Cl, Br, OCH3, COCH3, CH3, t-(CH3)3, C6H5) and 2,4-dimethoxyphenol, and the natural antioxidants eugenol and isoeugenol, were investigated using differential scanning calorimetry (DSC) by measuring their anti-1,1-diphenyl-2-picrylhydrazyl (DPPH) radical activity and the induction period for polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO). 2-Allyl-4-methoxyphenol and 2,4-dimethoxy-phenol scavenged not only oxygen-centered radicals (PhCOO*) derived from BPO, but also carbon-centered radicals (R*) derived from the AIBN and DPPH radical much more efficiently, in comparison with eugenol and isoeugenol. 2-Allyl-4-methoxyphenol may be useful for its lower prooxidative activity.

"Leaching or not leaching": an alternative approach to antimicrobial materials via copolymers containing crown ethers as active groups.

In this work, new copolymers containing either MMA and 18C6 crown-ether pendants, or PEG, MMA and 18C6 crown-ether pendants were synthesized to test the idea that sequestering structural alkali-earth ions from the bacterial outer membrane (OM) may lead to bacterial death. The copolymers were obtained either via uncontrolled radical polymerization or ATRP; the latter approached allowed us to produce not only linear copolymers but also branched Y-like structures. After checking for the capability of complexing magnesium and calcium ions, the antimicrobial activity of all copolymers was tested placing their casted plaques in contact with pure water E. coli suspensions. All plaques adsorbed alkali-earth ions and killed bacteria, albeit with different antimicrobial efficiencies. Differences in the latter characteristic were attributed to different plaque roughness. The role of the 18C6 crown-ether pendants was elucidated by pre-saturating plaques with Mg/Ca ions, the marked reduction in antimicrobial efficiency indicating that losing the latter from OM due to surface complexation does play an important role in killing bacteria at short (<5 h) contact times. At longer times, the mode of action is instead related to the poly-cationic nature acquired by the plaques due to ion sequestering.

Comparative dural closure techniques: a safety study in rats.

BACKGROUND: Some neurosurgical procedures have high morbidity and mortality rates due to cerebrospinal fluid (CSF) fistula development, particularly when dural defects are in relatively inaccessible areas or surrounded by friable dura. We used a rat model to test 4 different dural closure techniques to determine which one was significantly superior for achieving a watertight dural closure with minimal harm to brain tissue. METHODS: The rats were randomly divided into 2 groups. The first group (group A, n = 40) was used to test the strength of the adhesivity for CSF leakage. Histopathologic studies were used to evaluate the granulation tissue between the dura and dural graft. Effects on the brain tissue were studied in the second group (group B, n = 40) where lipid peroxidation was determined. These 2 groups consisted of 5 subgroups: control, methyl metacrylate, n-butyl cyanoacrylate, fibrin glue, and CO(2) laser. RESULTS: Methyl metacrylate and CO(2) laser techniques were inadequate for stopping dural leakage and had harmful effects on brain tissue. Cerebrospinal fluid leak was observed only in 1 rat in the n-butyl cyanoacrylate subgroup and this result was statistically significant (P = .0005), but lipid peroxidation levels for this material showed that it was not safe for dural closure in case it leaked through the dural defect. The lipid peroxidation levels of the fibrin glue subgroup were not statistically significantly different from the control group (P = .440). CONCLUSIONS: Fibrin glue was the safest material with a CSF leakage risk that was higher than n-butyl cyanoacrylate (25% vs 12.5%) but acceptable. This study showed no relationship between the CSF leak and histopathologic findings for sealant properties of the tissue adhesives.

Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats.

The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions.

Effects of acrylic resin monomers on porcine coronary artery reactivity.

The purpose of the present investigation was to assess the reactivity of porcine coronary arteries under in vitro conditions following their exposure to methyl methacrylate (MMA) and hydroxyethyl methacrylate (HEMA) monomers. Confirming previous studies using rat aortas, both MMA and HEMA induced acute/direct relaxation of coronary ring preparations, which was partly dependent on the endothelium. With prolonged tissue exposure, both monomers caused time- and concentration-dependent inhibition of receptor-mediated contraction of the vascular smooth muscle caused by prostaglandin F2∝ (PGF2∝), with HEMA causing more inhibition than MMA. Hydroxyethyl methacrylate, but not MMA, also produced impairment of non-receptor-mediated contraction of the coronary smooth muscle induced by KCl. On the other hand, neither HEMA nor MMA altered relaxation of the smooth muscle produced by the direct-acting pharmacological agent, sodium nitroprusside (SNP). While exposure to HEMA impaired endothelium-dependent vasorelaxation caused by bradykinin (BK), MMA markedly enhanced this endothelial-mediated response of the arteries. The enhanced endothelial response produced by MMA was linked to nitric oxide (NO) release. In conclusion, with prolonged tissue exposure, MMA causes less pronounced effects/adverse consequences on coronary smooth muscle function relative to the effect of HEMA, while enhancing vasorelaxation associated with release of NO from the endothelium. Accordingly, MMA-containing resin materials appear to be safer for human applications than materials containing HEMA.

The osteolytic response of macrophages to challenge with particles of Simplex P, Endurance, Palacos R, and Vertebroplastic bone cement particles in vitro.

The capacity of clinically relevant wear particles from Simplex P, Endurance, Vertebroplastic and Palacos R bone cements to activate macrophages to produce cytokines and bone resorbing activity in vitro was compared. Cement particles were generated aseptically by using a pin on plate rig. The particles were irregular in shape, and there were no significant differences in the particle characteristics of the different bone cement types (mean equivalent circle diameter range 0.225--0.36 mum, mean area range 0.048--0.063 microm(2), mean aspect ratio range 1.481--1.593, and mean length 0.412--0.523 microm). The volumetric concentration of particles in the 0.1- to 1.0-microm size range was 85% Palacos R, 82% Endurance, 80% Simplex P, and 77% Vertebroplastic. Particles were cultured with C3H macrophages at 100 microm(3) per cell for 24 h. Cytokines were determined by enzyme-linked immunosorbent assay and bone resorption (BR) measured by Ca(45) release from murine calvarias. Particles of Palacos R and Endurance stimulated enhanced production of TNF-alpha, IL-1-beta, and IL-6 (p<0.05; ANOVA). Simplex P particles only stimulated IL-1-beta (p<0.05; ANOVA). Vertebroplastic particles did not stimulate production of any of the cytokines. Particles of Palacos R generated the highest BR (1.38), but this did not reach statistical significance. The BRs for the other bone cements were no greater than the control. Hence, compared with the same volumetric concentrations, particles of Palacos R and Endurance were the most, and particles of Vertebroplastic were the least biologically reactive.

In vitro evaluation of the bioadhesive properties of hydrophobic polybasic gels containing N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate.

The bioadhesive properties of the hydrophobic, basic polyelectrolyte hydrogel disks containing crosslinked N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate 30/70mol% were evaluated in vitro using gastric (pH 1.2), sublingual (pH 6.5), vaginal (pH 4.0) and intestinal (pH 7.5) pig's mucosas. Adhesive strength was measured using a modified Du Noüy tensiometer by measuring the force of detachment between a gel disk and the respective mucosa. The effect of crosslinker content in the gel was evaluated. It was found an increase in the adhesive strength with the increase of crosslinker content in the pH range of 4.0-7.5. For the evaluation at pH 1.2 (gastric mucosa) the opposite behavior was observed. The results indicate that initial bioadhesive contact may be the result of surface energy effects and/or electrostatic interactions of oppositely charged groups between mucin and the gel. In some cases, mucus dehydration may also be involved. When the gel is swollen, chain interpenetration also plays a roll in the bioadhesive interaction. The gels presented bioadhesive forces in gastric and vaginal mucosas (acidic medium), similar to the adhesive forces of well-known bioadhesives such as hydroxymethylcellulose and sodium alginate to the intestinal mucosa. The results indicate that hydrophobic polybasic gels present bioadhesive properties that make them suitable for site specific, pH controlled drug delivery.

Synthesis, characterization, and blood compatibility of polyamidoamines copolymers.

This work reports the development of new non-thrombogenic polymers based on the linear polymers of polyamidoamines (PAAs), having heparin binding ability, obtained by polyaddition of secondary amines to N,N'-methylene bis-acrylamide. PAAs could not be used directly in the making of blood-contacting materials due to their poor mechanical strength. In order to overcome this lacuna, copolymers of amidoamine with methylmethacrylate (MMA) were prepared. Characterization studies indicated that the PAAs have been suitably incorporated into the MMA matrix. The relative hydrophilic nature of the synthesized copolymers was established from the measurement of water contact angle. The heparinized copolymers showed significant improvement in non-thrombogenic characteristics.

Differential regulation of in vitro cytokine production by human blood cells in response to methylmethacrylate.

The effect of methylmethacrylate (MMA) on human whole blood cultures (WBC) obtained from healthy donors was investigated. Lymphocyte transformation and cytokine production, that is, interleukin 6 (IL-6), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha), were used to evaluate the immunological activities of MMA. Primary cytotoxicity testing of MMA in Jurkat cells showed that this compound decreased the cell proliferation to 50% at a concentration of >60 mmol/L. Similarly, MMA significantly decreased lymphocyte transformation in either phytohemagglutinin (PHA) or Staphylococcus aureus protein A (SpA) activated WBC at 100 mmol/L. In contrast to activated WBC, MMA had no observed effect on resting blood cells. Cytokine expression in WBC seemed differentially modulated by MMA. There was a tendency for IL-6 production in both resting and PHA-stimulated WBC to be upregulated, while IL-6 induced in SpA stimulated cultures was downregulated. TNF-alpha was slightly increased by MMA in resting WBC at early incubation periods, and it was slightly downregulated in response to PHA or SpA activation. Suppression of IFN-gamma secretion was observed in WBC with or without PHA or SpA stimulation. The overall results demonstrated that MMA at physiological levels could influence the cytokine production in normal human blood cells in vitro. Alterations of cytokine production patterns by MMA indicate that this compound has multiple regulatory effects on immune reactions in normal human blood.