Copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) as biomaterials.

Copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) showed good hemocompatibility as hypothesized. The hypothesis was surfaces having phosphorylcholine groups by polymerization of MPC could accumulate phospholipids from blood stream and show good blood compatibility. We designed and prepared a methacylate having a phosphorylcholine group. While it was possible to introduce them by polymer reactions, polymer reaction is not always good method to prepare the desired pure surface. This must be very important point to consider biomaterials, as we have to apply them in our body without any adverse effects. The hypothesis was confirmed by changing copolymer composition. The adsorption amount of phospholipids on the surfaces increased with increasing the MPC units in the copolymers. On the other hand, increasing MPC units in MPC copolymers decreased adsorption amount of peptides. There is limitation in blood compatibility tests in vitro due to unstable characteristics of blood itself. We evaluated them with series of blood compatibility tests, in vitro, ex vivo and in vivo, on coated PMMA beads, modified hollow fibers for hemodialysis and 2 mm small diameter blood vessels, respectively. These data suggested MPC is a promising methacrylate to develop good blood contacting devises, which may not require systemic anticoagulation. Conventional blood compatible biomaterials were not suitable to make permeable membranes. But MPC is soluble in water and we could prepare permeable membranes to various solutes by the copolymerization. Introduction of MPC copolymers on cellulose and polysulfone hollow fiber membranes gave them nonthrombogenicity but it did not give adverse effect on their permeability. These data suggested that it is possible to apply them to hemodialyzers, oxygenators and percutaneous glucose sensors to keep diabetic patients easier. MPC surfaces are good hydrogel to minimize damage on tissues by lubricating between organs and the coated devices. They do not induce denaturation of peptides, which is beneficial to keep activities of enzymes longer. And poly-MPC dissolved is applicable to stabilize several bioactive peptides in aqueous phase. So MPC polymers are useful to minimize fouling by inhibiting the adsorption of bioactive proteins. MPC has high potential to develop many varieties of new biomaterials useful in so-called biotechnology. MPC and their copolymers are commercially available from NOF (Tokyo, Japan) and Biocompatibles (UK, as PC technology).

Influence of dentinal polyelectrolytes on wet demineralized dentin, a bonding substrate.

The objective of this study was to show the influence of dissolved dentinal polyelectrolytes on the characteristics of dentin (bonding substrate) demineralized by citric acid in the absence or presence of ferric chloride. The demineralizing agent was an aqueous mixture of 0, 1, 3, or 10% ferric chloride in 10% citric acid (10-0, 10-1, 10-3, 10-10, respectively). The hypothesis was that the concentration of dissolved dentinal noncollagenous substances, mainly polyelectrolytes soluble in water, must be decreased by their aggregation with ferric ions, which changes the characteristics of demineralized dentin, the rates of demineralization, and dehydration. Cervical bovine dentin was prepared in 3 x 2 x 2-mm blocks, each weighing 20.0 +/- 0.5 mg. The rate of demineralization was investigated by measuring the weight loss resulting from demineralization by immersion in 10 mL of conditioner at 2-h intervals. The dehydration rate of wet demineralized dentin was determined using two methods: (1) weight loss in a desiccator under 263 Pa pressure and (2) differential scanning calorimetry (DSC). Twenty, 12, 8, and 4 h were required to complete demineralization of the blocks with the 10-0, 10-1, 10-3, and 10-10 solutions, respectively. The 10-10 wet demineralized dentin showed the highest rate of dehydration, followed in descending order by the 10-3, 10-1, and 10-0 specimens. Ferric chloride in dentin conditioners provided both a higher rate of dentin demineralization and a higher dehydration rate of wet demineralized dentin. These results suggest that in the presence of ferric chloride, a decreasing amount of dissolved polyelectrolytes aggregated with ferric ions in the substrates may increase the permeability of dentin to water and citric acid. Improvement of monomer permeability is essential to the preparation of good hybridized dentin, providing a more stable and reliable bonding and also protecting the dentin and pulp from infection. A further study of bonding substrates is required in order to understand the role of hybridized dentin in improved dental treatment.

Preparation of non-thrombogenic materials using 2-methacryloyloxyethyl phosphorylcholine.

This review addresses the non-thrombogenic characteristics of copolymers based on 2-methacryloyloxyethyl phosphorylcholine (MPC), originally developed by Nakabayashi and colleagues. The hypothesis underlying these developments was that such materials would adsorb phospholipids from blood, yielding surfaces with good natural blood compatibility. Methacrylates were found to have excellent properties for this copolymerisation. The characteristics of the MPC copolymers relevant to the improved blood compatibility were minimisation of protein adsorption through an increase in the amount of free water in the MPC hydrogels, which prevents protein conformational change and increased protein stability in solution. Non-thrombogenicity has been evaluated by in vitro, ex vivo and in vivo procedures. Non-thrombogenic dialysis membranes and a durable glucose biosensor have been developed using this MPC copolymer.

Beneficial effects of synthetic phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate), on stratum corneum function.

The effects of a newly synthesized phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) [poly(MPC-co-BMA)], on the water barrier function and water-holding capacity of the stratum corneum were examined by measuring transepidermal water loss (TEWL) and electrical conductance of the skin surface. On the backs of four NC mice, the epidermal permeability barrier was abrogated by cellophane tape stripping 30 times. The skin was then treated with 0.1% poly(MPC-co-BMA) or distilled water twice daily for the following 3 days. Poly(MPC-co-BMA) reduced TEWL significantly compared with the control after the first treatment (P = 0.044) and this effect was observed for 3 days. In human skin, water-holding capacity was measured at 5, 10, 15, 30 min and 1, 2, and 4 h after the application of poly(MPC-co-BMA) or distilled water to both volar forearms of 21 healthy volunteers. Skin treated with poly(MPC-co-BMA) showed significantly greater ability to retain water at all time points. Poly(MPC-co-BMA) is the first synthetic material that can enhance both the water barrier function and water-holding capacity of the stratum corneum. Our results indicate that this substance may be useful clinically in the treatment of dry skin.

Effect of Phenyl-P/HEMA acetone primer on wet bonding to EDTA-conditioned dentin.

OBJECTIVES: The purpose of this study was to examine the effect of 2-methacryloyloxyethyl phenyl phosphoric acid (Phenyl-P)/2-hydroxyethyl methacrylate (HEMA) acetone-based primer on moist dentin surfaces that were preconditioned with ethylenediaminetetraacetate (EDTA) to remove the smear layer. METHODS: Bovine dentin were prepared with 180-grit paper, conditioned with 0.5M EDTA (pH 7.4) for 60s followed by water rinsing and then blot drying. Each surface was then primed with Phenyl-P/30 wt% HEMA in acetone for 10s followed by blot drying. A light-cured bonding agent was then applied, cured and trimmed to give dumbbell-shaped specimens. The Phenyl-P concentration ranged from 1 to 20 wt%. During the bonding procedure, no compressed air was used. After storage in water at 37 degrees C for one day, tensile bond strengths were measured and analyzed using one-way ANOVA. Dentin discs treated under the same conditions were observed under a scanning electron microscope (SEM). RESULTS: When the concentration of Phenyl-P was 12 wt%, the highest mean tensile bond strength was obtained (27 MPa). It was significantly higher than that of the 3, 5, 15 or 20 wt% groups (9-11 MPa) (p<0.05). The samples of 1 wt% group were all broken during trimming the dumbbell-shaped specimens. SEM observations showed a 1 microm-thick layer of hybridized dentin after polished cross-sections were chemically challenged with 6N HCl for 30s and then 1% NaOCl for 60 min. SIGNIFICANCE: The experimental Phenyl-P/HEMA acetone primer is effective in bonding resin to EDTA-conditioned dentin. Acetone as a solvent for Phenyl-P/HEMA primer has the clinical advantage of not requiring an air-stream to evaporate the solvent. The experimental bonding procedure can minimize the skin irritation by HEMA.

Preservation of platelet function on 2-methacryloyloxyethyl phosphorylcholine-graft polymer as compared to various water-soluble graft polymers.

The chemical structures of water-soluble polymers grafted onto PE surfaces affect platelet function when the platelets contact the polymer surfaces. To improve our understanding of this effect, this study sought to control the blood/materials interaction on the surfaces of polyethylene (PE) by grafting with various water-soluble polymers. Such polymers as poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(acrylamide) (PAAm), poly(N-vinylpyrrolidone) (PVPy), and poly[monomethacryloyl poly(ethylene glycol)] (PMPEG) were grafted on low-density PE sheets by photoinduced graft polymerization. Both the PE bags modified with water-soluble polymers and those nonmodified were prepared by heat processing. Activation of platelets after storage in the PE bags was evaluated by measuring the cytoplasmic free calcium ion concentration ([Ca(2+)]i). The concentration of [Ca(2+)]i of platelets in contact with the PE surface grafted with PMPC was the same as that of native platelets and significantly less than that in contact with other PE surfaces grafted with water-soluble polymers. The number of adherent platelets was effectively decreased on PE surfaces grafted with PMPC and PMPEG, as compared with nontreated PE. The aggregation ability of platelets was also measured after storage of platelet-rich plasma in the PE bags. The PE surface grafted with PMPC effectively maintained aggregation ability as compared with both the nontreated PE and with PE grafted with PAAm, PVPy, and PMPEG. It was concluded that for preserving platelet function, PMPC was the most effective of these water-soluble polymers used for surface modification.

Preparation of nanoparticles composed with bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer.

The poly(L-lactic acid) nanoparticles immobilized with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, which has excellent blood compatibility, were prepared by a solvent evaporation technique using the water-soluble amphiphilic MPC polymer as an emulsifier and a surface modifier. The diameter and zeta-potential of the obtained nanoparticles strongly depended on the concentration of the MPC polymer. When the nanoparticles were prepared in 1.0 mg/ml of an MPC polymer aqueous solution, the diameter was 221 nm which was determined by atomic force microscopy and dynamic light scattering measurements. The X-ray photoelectron spectroscopic analysis indicated that the phosphorylcholine groups of the MPC unit were located at the surface of the nanoparticles, that is, the MPC polymer was immobilized on the PLA particles and the surface zeta-potential was -2.5 mV. Various hydrophobic fluorescence probes could permeate through the MPC polymer layer and adsorb on the PLA surface. The amount of bovine serum albumin adsorbed on the nanoparticles was significantly smaller compared with that on the conventional polystyrene nanoparticles. It is suggested that the nanoparticles immobilized with the MPC polymer have the potential for use as both a novel drug carrier and diagnostic reagent which can come in contact with blood components.

Bonding to dentin with a self-etching primer: the effect of smear layers.

OBJECTIVE: The purpose of this study was to investigate the effect of smear layers on the tensile bond strength to human dentin. Bond strength was determined on dumbbell-shaped specimens to determine the feasibility for clinical use of a self-etching primer. METHODS: The dentin of extracted human teeth was exposed by grinding with either #180 or #600 abrasive paper. A self-etching primer was then applied to the prepared dentinal surfaces and left undisturbed for 30s. It was then air-dried and a photocured bonding agent applied and irradiated for 20s. A composite resin was then added to the primed dentin and light-cured for 60s to complete the bonded assemblies. Mini-dumbbell specimens (3.0 x 2.0 mm2) were prepared from the bonded samples. These specimens were stored in 37 degrees C water for 24h before tensile loading to failure at a crosshead speed of 1.0 mm/min. Surfaces of fractured specimens, both resin and dentin, were examined under a scanning electron microscope (SEM). RESULTS: Significantly different tensile bond strengths (TBS) of 10.0+/-7.2 and 28.5+/-5.2MPa were found for #180- and #600-prepared dentin, respectively (p<0.01). The former specimens fractured within the hybridized, relatively coarse smear layer, while the latter demonstrated adhesive failure between the composite resin and an attached PMMA rod, not between the dentin and applied adhesive agent. SIGNIFICANCE: The presence and quality of a smear layer yields significantly different bond strengths to prepared human dentin, in vitro. However, a TBS of 10+/-7MPa is evidently adequate, since self-etching primers have been well accepted in dental clinics.

Effect of dentin conditioners on wet bonding of 4-META/MMA-TBB resin.

PURPOSE: By altering either ferric chloride concentration in 10% citric acid (1% ferric chloride = 10-1; 5% ferric chloride = 10-5; 10% ferric chloride = 10-10) or conditioning periods with an aqueous mixture of 1% citric acid and 1% ferric chloride (1-1), the influence of dentin substrate on bond strength and hybridized dentin in wet bonding of 4-META/MMA-TBB resin was examined. MATERIALS AND METHODS: Dentin surfaces of fresh bovine incisors were conditioned either with 10-1, 10-5, or 10-10 mixtures for 10 s (10-1-10s, 10-5-10s, 10-10-10s groups) or with a 1-1 mixture for 5, 10, 30 or 60 s (1-1-5s, 1-1-10s, 1-1-30s, 1-1-60s groups). Rinsed, demineralized dentin samples were kept wet, primed with 5% 4-META in acetone for 60 s, and bonded with 4-META/MMA-TBB resin. Bonded specimens were trimmed to a mini-dumbbell shape for tensile testing. The cross sections of bonded specimens were modified with HCl and NaOCl in order to assess the hybrid layer. The fractured surfaces of specimens and the hybridized dentin were investigated with SEM. RESULTS: No significant difference (p > 0.01) in tensile strength was identified between 10-1-10s and 10-5-10s groups (30 MPa), 10-10-10s and 1-1-5s groups (15 MPa), and the three groups conditioned by 1-1-10s, -30s and -60s (40 MPa). The thickness of the hybrid layer increased with increasing either ferric chloride or conditioning periods. CONCLUSION: The concentration of ferric chloride in 10% citric acid for wet bonding must be less than 5% in order to provide a reliable bond. When applied from 10 to 60 s, the 1-1 conditioner provided hybridized dentin with reliable tensile bond strength. The thickness of the hybrid layer did not influence the tensile bond strength.

Semi-interpenetrating polymer networks composed of biocompatible phospholipid polymer and segmented polyurethane.

2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers, which have excellent biocompatibility, have been receiving increasing attention in biomedical and bioengineering fields; however, the mechanical strength of the hydrated MPC polymers is not sufficient for use in these fields as a bulk material. Therefore, we hypothesized that a novel material might be realized by reinforcing the MPC polymer network with segmented polyurethane (SPU). Semi-interpenetrating polymer networks (IPNs) composed of crosslinked MPC polymer and SPU were prepared. The mechanical properties of the IPN membrane were significantly improved compared with those of the MPC polymer membrane. Three-dimensional polymer networks of the MPC polymer in the IPNs were observed after solvent extraction of SPU. An X-ray photoelectron spectrum analysis revealed that the MPC units were exposed on the IPN surface. When the IPN was alternately soaked in water and ethanol, the swelling ratio was found to be completely reversible and no disintegration of the network structure was observed. The permeation coefficient of 1, 4-di(2-hydroxyethoxy)benzene through the IPN membrane was 1.11 x 10(-7) cm(-2)s(-1). The amount of adsorbed protein and the number of adherent platelets on the IPN membrane were effectively reduced compared with those on SPU. We concluded that IPNs composed of the MPC polymer and SPU are a new bulk biomaterial, which possesses both blood compatibility and good mechanical properties.

The effect of phosphoric acid concentration on resin tag length and bond strength of a photo-cured resin to acid-etched enamel.

OBJECTIVES: To determine the relationship between depth of penetration and tensile bond strength of a photo-cured resin to phosphoric acid etched enamel, and the efficacy of enamel etchants that are less aggressive than a concentration of 10% H3PO4. METHODS: The tensile bond strength and length of tags produced by a photo-cured (20 s) resin consisting of pre-polymerized TMPT/silica in 3% HNPM-TEGDMA on acid-etched enamel was determined. The enamel etchants tested were various concentrations (3-65%) of phosphoric acid. The resin was applied to enamel samples that had been abraded with No. 600-grit SiC paper and acid etched (30 s) to create test specimens that were loaded to fracture on a testing device. The HCl-treated, then cut specimens, were examined under scanning electron microscopy and light microscopy. RESULTS: The tensile bond strength (10 MPa) of resin to enamel, pre-treated with various acid concentrations did not vary significantly. But resin tag length was found to decrease significantly from 22 microns for 35% H3PO4 to 12 microns for 20% H3PO4 to 9 microns for 5, 10 and 65% H3PO4 to 5 microns for 3% H3PO4. SIGNIFICANCE: These findings suggest that the length of the tags created by the tested photo-cured resin on phosphoric acid-etched enamel contributes little to the bond strength of the test specimens, and that the adhesive strength of the resin to H3PO4 etched enamel is mainly attributable to the resin's ability to penetrate between the enamel crystallites and rods. Further, enamel pre-treatment by phosphoric acid etchants of concentrations lower than 10% may be satisfactorily employed. The use of less aggressive acid concentrations might minimize any potential adverse effects to enamel substrates.

Photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on polyethylene membrane surface for obtaining blood cell adhesion resistance.

Phospholipid polymer, poly[2-methacryloyloxyethyl phosphorylcholine (MPC)], was grafted with polyethylene (PE) membrane using photoinduced polymerization technique to make the membrane resistant to cell adhesion. The water contact angle on the PE membrane grafted with poly(MPC) decreased with an increase in the photopolymerization time. This decrease corresponded to the increase in the amount of poly(MPC) grafted on the PE surface. The same graft polymerization procedure was applied using other hydrophilic monomers, such as acrylamide (AAm), N-vinylpyrrolidone (VPy) and methacryloyl poly(ethylene glycol) (MPEG). These monomers were also polymerized to form grafted chains on the PE membrane, and the grafting was confirmed with X-ray photoelectron spectroscopy. Analysis of amount and distribution of plasma proteins at the plasma-contacting surface of the original and the modified PE membranes were analyzed using immunogold assay. The grafting of poly(MPC) and poly(VPy) on PE membrane reduced the plasma protein adsorption significantly compared with that on the original PE membrane. However, the PE membranes grafted with poly(AAm) or poly(MPEG) did not show any effects on protein adsorption. Platelet adhesion on the original and modified PE membranes from platelet-rich plasma was also examined. A large number of platelets adhered and activated on the original PE membrane. Grafting with poly(AAm) did not suppress platelet adhesion, but grafting with poly(MPC) or poly(VPy) on the PE membrane was effective in preventing platelet adhesion. It is concluded that the introduction of the phosphorylcholine group on the surface could decrease the cell adhesion to substrate polymer.

Prevention of fibrous layer formation between bone and adhesive bone cement: in vivo evaluation of bone impregnation with 4-META/MMA-TBB cement.

We have studied a new adhesive bone cement, that consists of 4-methacryloyloxyethyl trimellitate anhydride (4-META) and methylmethacrylate (MMA) as monomers, tri-n-butyl borane (TBB) as the initiator, and polymethylmethacrylate powder (4-META/MMA-TBB cement). This cement has shown remarkable adhesive properties to bone in vitro. In this study, we assessed the interface in vivo periodically. The femora of rabbits were fenestrated and filled with either the 4-META/MMA-TBB cement or a conventional polymethylmethacrylate cement. The animals were killed after 1, 4, 12, and 24 weeks to analyze the interface by optical microscopy and transmission electron microscopy. Optical microscopic examinations showed that the cured 4-META/MMA-TBB adhesive cement bonded to bone directly for 24 weeks, whereas a fibrous tissue layer was observed between the bone and cured conventional cement at 12 weeks after the operation. The transmission electron microscopy views of 4-META/MMA-TBB cement bonded to bone demonstrated a unique "hybridized bone" with the cement in the subsurface of the substrate in every case. The formation of the hybridized bone indicates the bonding mechanism of the adhesive cement to bone, which prevents the fibrosis intervention between bone and cement. These results suggest that the biomechanical and adhesive properties of 4-META/MMA-TBB cement make it a useful bone-bonding agent in orthopedic surgery.

In vivo evaluation of the bond strength of adhesive 4-META/MMA-TBB bone cement under weight-bearing conditions.

In order to minimize the problems associated with implant fixation using acrylic bone cement, we studied a new adhesive bone cement that consists of 4-methacryloyloxyethyl trimellitate anhydryde (4-META) and methylmethacrylate (MMA) as monomers, tri-n-butylborane (TBB) as an initiator, and PMMA powder (4-META/MMA-TBB cement). It shows remarkable adhesive properties to metal and bone in vitro. The purpose of this study was to evaluate the strength of the bond of the cement to both metal and bone in vivo under weight-bearing conditions. Metal prostheses were implanted in the right femora of 12 rabbits using either adhesive 4-META/MMA-TBB cement or the conventional PMMA cement, as the control, for fixation. After 4 and 12 weeks, both femora were excised and the same operations were performed in the left femora in vitro. Eighteen femora were sectioned for the mechanical assessment of the bone-cement and cement-implant interfaces. 4-META/MMA-TBB cement had a significantly higher interfacial shear strength than the conventional PMMA cement: 201 N and 90 N, on average, for the implant-cement interface (p<0.01); and 138 N and 89 N, on average, for the bone-cement interface (p<0.01), at 12 weeks. The present results suggest the efficacy of 4-META/MMA-TBB cement in providing greater fixation of implants to bone and promise a firmer intramedullary fixation than the control conventional PMMA cement.

Effect of etchant variation on wet and dry dentin bonding primed with 4-META/acetone.

OBJECTIVE: To collect data that explains the advantage, if any, of wet bonding versus dry bonding to dentin, and to more clearly understand the mechanism of wet bonding. METHODS: Bovine dentin samples were prepared with #600-grit paper and were divided into four groups of six each. The first six specimens were etched with 10% citric acid and 3% ferric chloride for 10 s then rinsed and blot-dried (Gr. 1: 10-3:W). The second six were etched with 10% citric acid and 3% ferric chloride then rinsed and air-dried (Gr. 2: 10-3:D). The third six were etched with 10% citric acid for 10 s, rinsed and blot-dried (Gr. 3: 10-0:W). The fourth group of six samples was etched, rinsed and air-dried (Gr. 4: 10-0:D). All groups were primed with 5% 4-methacryloyloxyethyl trimellitate anhydride (4-META) in acetone for 60 s and an acrylic rod was bonded to the samples using a 4-META/methyl methacrylate (MMA)-tri-n-butyl borane (TBB) resin. The samples were fashioned into dumbbell-shaped specimens and stressed in tension until bond failure, to determine tensile bond strengths. Fractured surfaces were examined by scanning electron microscopy. RESULTS: The mean tensile bond strengths of specimen groups were found to be 18.9 (8.1) MPa (Gr. 1: 10-3:W), 18.1 (1.7) MPa (Gr. 2: 10-3:D), 11.9 (4.4) MPa (Gr. 3: 10-0:W) and 5.4 (2.8) MPa (Gr. 4: 10-0:D). There was no statistically significant difference between Grs. 1 and 2 (p > 0.01), or between Grs. 1 and 3 (p > 0.05). The TBS of Gr. 4 (10-0:D) was significantly lower than the others (p < 0.01). The 5% 4-META in acetone primer was apparently quite effective in improving monomer impregnation into demineralized dentin resulting in increased resin content within the hybridized dentin. SIGNIFICANCE: Effective dentin bonding depended upon the etchants employed. 10-0 etching and air-drying caused the demineralized dentin to collapse in which case wet bonding became necessary to obtain good TBS data. The specimens demineralized with 10-3 did not collapse, even when air-dried; consequently both wet and dry bonding proved effective for obtaining high tensile bond strength data.

Small diameter vascular prosthesis with a nonthrombogenic phospholipid polymer surface: preliminary study of a new concept for functioning in the absence of pseudo- or neointima formation.

The purpose of this study was to prepare a small diameter vascular prosthesis functioning without pseudointima formation. A nonthrombogenic phospholipid polymer, the 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, has a cell membrane-like structure and has demonstrated strong nonthrombogenicity. We have recently prepared 2 kinds of vascular prostheses, 2 mm in diameter, composed of the MPC polymer and segmented polyurethane (SPU). One includes 7.5 wt% MPC polymer (SPU/MPC[7.5] prosthesis), and the other includes 10.0 wt% (SPU/MPC[10] prosthesis). These prostheses were placed in rabbit carotid arteries and were retrieved at 1 and 4 weeks after implantation. A pseudointima was observed at 4 weeks on the SPU/MPC(7.5). For the SPU/MPC(10), the surface was macroscopically clear without a pseudointima even after a 4 week implantation. It appears that the SPU/MPC(10) prosthesis, functioning without a pseudointima, possesses a stronger nonthrombogenicity and would be more applicable for clinical use.

Restoration of segmental bone defects in rabbit radius by biodegradable capsules containing recombinant human bone morphogenetic protein-2.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) was encapsulated in biodegradable poly(DL-lactide-co-glycolide) (PLGA) capsules to regenerate bone by controlling the release rate of rhBMP-2. The rhBMP-2/PLGA capsules containing 12 microg of rhBMP-2 were implanted in seven 15-mm segmental defects of rabbits radii to examine the healing capacity of the rhBMP-2/PLGA capsules. For the control group, four segmental defects were left empty and two were implanted with ghost PLGA capsules. Healing of the defects was followed for 24 weeks and periodically evaluated by radiographs and histological examination. Mechanical testing was applied to three regenerated bone samples at 24 weeks postoperatively when the mature cortex was observed. Mechanical properties of regenerated bone were not significantly different from normal intact bone statistically. Histologically, the rhBMP-2/PLGA capsules disappeared completely during the process of bone regeneration. These results increased possibilities for clinical application of rhBMP-2/PLGA capsules.

Chemical modification of silk fibroin with 2-methacryloyloxyethyl phosphorylcholine. II. Graft-polymerization onto fabric through 2-methacryloyloxyethyl isocyanate and interaction between fabric and platelets.

2-Methacryloyloxyethyl phosphorylcholine (MPC) was grafted onto silk fabric in a two-step heterogeneous system through the vinyl bonds of 2-methacryloyloxyethyl isocyanate (MOI) modified on the fabric. First, habutae silk fabric was modified with the MOI monomer in anhydrous dimethyl sulfoxide using di-n-butyltin (IV) dilaurate and hydroquinone at 35 degrees C. The saturated weight gain of modified MOI monomer on the fabric was 7.3 wt% versus the original silk. Second, graft polymerization with MPC onto the MOI modified silk was conducted using 2,2'-azo bis[2-(2-imidazolin-2-yl)propane dihydrochloride] (VA-044) as an azo polymerization initiator. The weight of the grafted MPC eventually gained was about 26.0 wt%. The MOI-modified and MPC-grafted silk fabrics were analyzed by Fourier transform infrared (FT-IR) spectroscopy. To confirm the improved biocompatibility of the silk fabric, platelet adhesion was preliminarily tested measuring lactate dehydrogenase. The number of platelets adhering to polyMPC-grafted silk fabric decreased by about one tenth compared to original and MOI-modified silk after 60 min of contact with human platelet-rich plasma (1.0 x 10(6) platelets cm(-2)).

Inhibition of fibroblast cell adhesion on substrate by coating with 2-methacryloyloxyethyl phosphorylcholine polymers.

Fibroblast adhesion and growth behavior were examined on various polymers coated on a poly(ethylene telephthalate) (PET) substrate. The polymers are poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylatel copolymer (PMB)s with different MPC unit compositions, and poly(2-hydroxyethyl methacrylate). Surface analysis by dynamic contact angle measurement revealed that the mobility of the polymer chain on the PET substrate depended on the MPC unit composition, but there was no significant difference between the PMBs with 3-10 mol% MPC units and poly(HEMA). Fibronectin adsorption on the polymer surface from a cell culture medium was determined by immunoassay. The adsorbed fibronection was evenly distrubuted in every polymer, however, the amount was reduced with an increase in the MPC unit composition in the PMB. This result suggested that the MPC unit could weaken the interaction between the polymer surface and proteins. When fibroblast L-929 cells, were cultured on the polymers, the cells adhered and the number of cells increased on not only the hydrophobic poly(BMA) but also on the hydrophilic poly(HEMA). However, the number of cells that adhered on the PMB surface decreased with an increase in the MPC unit composition. This was a result of the fibronectin adsorption behavior. Thus, it could be concluded that since the PMB could suppress cell adhesion proteins e.g. fibronectin, the PMB showed excellent cell adhesive resistance properties.