Activation of complement in human serum by some synthetic polymers used for intraocular lenses

Determination of the potential to activate complement can be used as one criterion in testing the biocompatibility of various synthetic polymers that are utilized in the medical field. Intraocular lenses (IOLs) made of poly(methyl methacrylate) (PMMA) with PMMA loops, poly(hydroxyethyl methacrylate) (PHEMA) lenses, silicone lenses, and PMMA lenses with polypropylene loops were examined in this study. The concentrations of the activation peptides C3a, C4a and C5a were measured by radioimmunoassay (r.i.a.) in human serum after incubation with and without IOLs for up to 12 h. The presence of silicone lenses caused an increase in C3a levels. In the presence of polypropylene loops, the concentrations of both C3a and C5a were significantly higher than in serum incubated alone. There was no statistically significant increase in the concentration of C4a caused by any of the materials tested. The results suggest that IOLs made from silicone or lenses with polypropylene loops activate the complement system via the alternative pathway.     

Poly(2-hydroxyethyl methacrylate) biomimetic coating to improve osseointegration of a PMMA/HA/glass composite implant: in vivo mechanical and histomorphometric assessments

Bone implants must simultaneously satisfy many requirements, even though the surface properties remain a crucial aspect in osseointegration success. Since a single material with a uniform structure cannot satisfy all of these requirements, composite materials specifically designed for orthopedic or dental implant application should be envisaged. Two poly(methylmethacrylate)/hydroxyapatite composites reinforced by E-glass fibres, uncoated (PMMA/HA/Glass) and poly(2-hydroxyethyl methacrylate) (PMMA/HA/Glass+pHEMA) coated by the biomimetic method, were mechanically (push-out test) and histomorphometrically (Affinity Index, AI) investigated in an in vivo rabbit model. Cylindrical implants (diameter 2 mm x 5 mm length) were inserted into rabbit femoral cortical (mid-diaphysis) and cancellous (distal epiphysis) bone, under general anesthesia. The highest values of push-out force and ultimate shear strength were observed for the PMMA/HA/Glass at 12 weeks, which significantly (p < 0.001) differed from those of PMMA/HA/Glass+pHEMA at the same experimental time and from those of PMMA/HA/Glass at 4 weeks. At both experimental times, significantly (p < 0.0005) lower values of AI were observed in the PMMA/HA/Glass+pHEMA versus PMMA/HA/Glass (distal femoral epiphysis: 4 weeks = 33%; 12 weeks = 19%; femoral diaphysis: 4 weeks = 15%; 12 weeks = 11%). The good mechanical and histomorphometric results obtained with PMMA/HA/Glass should be followed by further evaluation of bone remodeling processes and mechanical strength around loaded PMMA/HA/Glass implants at longer experimental times. Finally, the biomimetic method applied to pHEMA needs to be further investigated in order to improve the positive effect of SBF on pHEMA and to enhance the coating adhesion.     

Suspension polymerization of 2-hydroxyethyl methacrylate in the presence of polymeric diluents: a novel route to spherical highly porous beads for biomedical applications

Spherical, highly porous beads of poly(2-hydroxyethyl methacrylate) (PHEMA) cross-linked with ethylene glycol dimethacrylate (EGDM) were prepared by suspension polymerization of HEMA in concentrated NaCl solutions in presence of toluene, poly(methyl methacrylate) (PMMA) in toluene, and poly(tetramethylene glycol) (PTMG). Magnesium hydroxide prepared in situ in the dispersion medium gave the best stabilization effect for the monomer droplets. In the presence of PTMG, beads having nearly 1.0 mm in diameter could be prepared, while toluene alone as the diluent produced beads of very small size. Removal of PMMA or PTMG from the beads after polymerization using suitable solvents gave rise to highly porous PHEMA microspsheres. Polymerization in the presence of PTMG produced microspsheres with better spherical geometry as compared to those generated in the presence of PMMA. The effect of various factors such as NaCl concentration, concentration of Mg(OH)2, and the concentration of PMMA or PTMG in the monomer phase on the stability of the suspension and the particle size distribution was investigated.     

Ultrathin coating by plasma polymerization applied to corneal contact lens.

Plasma coating (deposition of polymer under the influence of plasma) is utilized to modify the surface properties of corneal contact lens. An ultrathin layer (thickness of roughly 200 A) of plasma polymer of acetylene/H20/N2 is applied to poly(methyl methacrylate) (PMMA) corneal contact lenses. The surface becomes highly wettable with water compared to uncoated lens. When coated and uncoated contact lenses are placed on rabbit eyes, a remarkable difference in accumulation of mucous matter is observed. With the control lenses, the accumulation of mucous matter in a week is sufficient to affect the optical clarity of the lenses, whereas the coated lenses show no change after three months continuous wearing. The comparative degree of adhesion of the corneal epithelium cells onto glass, modified glass, PMMA, and coated PMMA surfaces is studied using tissue cultures and phase contrast microscopy. The coated PMMA surface exhibits a degree of tissue adhesion lower than that of control PMMA and higher than that of glass surface, and no sign of toxicity of the coated surface is observed by the tissue cultures.     

Preparation and evaluation of radiopaque hydrogel microspheres based on PHEMA/iothalamic acid and PHEMA/iopanoic acid as particulate emboli

Highly porous poly(2-hydroxyethyl methacrylate) (PHEMA) microspheres prepared by suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) in presence of polymeric diluents such as poly(methyl methacrylate) (PMMA) in toluene and poly(tetramethylene glycol) (PTMG) were made radiopaque by esterification of the reactive hydroxyl groups with iothalamic acid and iopanoic acid, two radiopaque substances clinically used. Of the various solvents and catalysts examined, tetrahydrofuran (THF) and N,N'-dimethyl paratoluidine (DMPT) were found to be best for obtaining a high degree of conversion. More than 30 wt% iodine could be bound to the microspheres which made them sufficiently radiopaque to be imaged radiographically. Microspheres retained their porosity, swelling ability, hydrophilicity, and surface morphology to a significant extent after iodination. Preliminary implantation studies of such microspheres subcutaneously in rats have shown no adverse tissue reactions over a 6-month period. It is suggested that these microspheres would prove to be useful as particulate emboli in endovascular embolization.     

Protection and polymerization of functional monomers, 23. Synthesis of well-defined poly(2-hydroxyethyl methacrylate) by means of anionic living polymerization of protected monomers

Anionic polymerizations of 2-[(trimethylsilyl)oxy]ethyl methacrylate ( 1 ), 2-[(tert-butyldimethylsilyl)oxy]ethyl methacrylate ( 2 ), and 2-[(methoxymethyl)oxy]ethyl methacrylate ( 3 ), the protected forms of 2-hydroxyethyl methacrylate (HEMA), were carried out in THF at ?78°C with 1,1-diphenylhexyllithium or 1,1-diphenyl-3-methylpentyllithium in the presence of LiCl. The resulting poly( 1–3 )s were found to possess predictable molecular weights and very narrow molecular weight distributions. The sequential polymerizations of tert-butyl methacrylate with the anionic propagating ends of poly( 1–3 ) gave block copolymers in quantitative efficiency. Thus, the anionic polymerizations of 1–3 proceeded without transfer and termination reactions to afford stable living polymers. Complete hydrolysis of the protective groups of poly( 1–3 )s produced linear poly(HEMA) quantitatively. Novel well-defined di- and triblock copolymers containing hydrophobic [polystyrene, poly(4-octylstyrene), polyisoprene] and hydrophilic segments [poly(HEMA)] were also prepared by sequential polymerization of the corresponding hydrophobic comonomers with 1 , followed by deprotection.     

Silicone rubber-hydrogel composites as polymeric biomaterials. I. Biological properties of the silicone rubber-p(HEMA) composite

A composite material was prepared consisting of silicone rubber matrix and particulate lightly cross-linked poly(2-hydroxyethyl methacrylate) (p(HEMA] hydrogel. The material resembling common silicone rubber is hydrophilic and swells in water like hydrogels. The effects of the implanted composite on tissues of the living organism were tested in rats by methods assessing local acute and chronic inflammatory reactions and calcification by means of radioactive indicators and by histological examination. Results of a 6 month implant study indicated no difference in reactions of the animal body on the silicone rubber-p(HEMA) composite and a non-toxic, non-irritant pure solid p(HEMA) control.     

The effect of charged groups on protein interactions with poly(HEMA) hydrogels

Proteins, lipids and other biomolecules interact strongly with the acrylic-based biomaterials used for contact lenses. Although hydrogels are nominally resistant to protein fouling, many studies have reported considerable amounts of protein bound to poly(2-hydroxyethylmethacrylate) (PHEMA) lenses. This study examined the binding of a series of biomolecules (tear protein analogues, mucin and cholesterol) to poly(methylmethacrylate) (PMMA) and three HEMA-based hydrogels (PHEMA, HEMA plus methacrylic acid (P(HEMA-MAA)), HEMA plus methacrylic acid plus N-vinylpyrrolidone (P(HEMA-MAA-NVP))) by use of a quartz crystal microbalance with dissipation (QCM-D) monitoring. The QCM-D estimates changes in the mass and viscous constant for the adsorbed layer through measurements of frequency and dissipation. Protein interaction with each of the test materials caused a net increase in mass of the material indicating protein binding except for lysozyme interacting with P(HEMA-MAA). A net decrease in mass was observed for lysozyme interacting with P(HEMA-MAA) which may be ascribed to lysozyme collapsing the hydrogel by expelling water. A net mass decrease was observed for cholesterol interacting with each of the hydrogel materials, while a mass increase was observed on PMMA.     

Implantation of p(HEMA)-collagen composite into bone.

The replacement of bone defects is very important in clinical practice. This study compares biological properties of poly(2-hydroxyethyl methacrylate)-collagen composite with those exhibited by pure p(HEMA), an insoluble fraction of calf skin collagen (ISC-40) and demineralized bone matrix after implantation into pig or dog femurs. The levels of biodegradation or destruction of implants and healing of bone defects were studied using X-ray photography, histology and enzyme histochemistry. The results indicated a significant effect of collagen on biological destruction of the p(HEMA)-composite implants; even a minute amount of collagen influences this process dramatically. A stimulatory action of collagen on new bone formation may be of importance in bone defect healing.     

激光泪道成形术治疗泪道阻塞的临床观察

目的 观察激光泪道成形术治疗泪道阻塞的效果及复发病例再次激光联合插管治疗的效果。方法 采用Nd：YAG激光泪道成形术治疗泪道阻塞102例。132眼。对复发病例。再次行激光联合插管治疗。结果 113眼一次治愈，有效9眼。术后10眼复发，再次行激光联合插管治疗，7眼治愈，3眼未愈。本组总治愈率90．9％，有效率97．7％。结论 Nd：YAG激光泪道成形术治疗泪道阻塞操作简单，安全有效，复发病例联合插管治疗可以提高治愈率。     

宫腔镜下Nd:YAG激光治疗子宫内疾病78例分析

目的 :评价宫腔镜对子宫内疾病的诊断价值和采用Nd :YAG激光治疗子宫内疾病的效果。方法 :对 78例子宫内疾病 (包括子宫内粘连、子宫粘膜下肌瘤、子宫纵隔、子宫粘膜息肉、宫颈息肉及宫颈管囊肿 )采用宫腔镜进行诊断 ,并用Nd :YAG激光进行治疗。结果 :宫腔镜诊断子宫内疾病的准确率高于超声诊断及放射诊断。采用Nd :YAG激光治疗的一次性成功率为 97.43 %。手术时间为 2 0 5 5分钟 ,平均 3 5 .7± 18.5分钟。无明显并发症。术后 1 3个月随访 2例病人有残留的粘连带及纵隔组织而进行二次手术。其余患者均恢复正常。 8例患者 (有生育要求者 )在一年内妊娠。结论 :对于子宫内疾病宫腔镜有较高的临床价值 ,采用Nd :YAG激光治疗具有更简便、安全、疗效确切等优点 ,具有广泛的应用前景     

强脉冲光联合Nd:YAG激光治疗黄褐斑疗效观察

目的:探讨强脉冲光联合Nd:YAG激光治疗黄褐斑的疗效。方法:60例患者按治疗方法不同分成3组:强脉冲光组、Nd:YAG激光组、联合组（强脉冲光联合Nd:YAG激光组）,每组20例患者,观察3组患者疗效和副作用。结果:3组之间疗效两两比较采用Mann-Whitney秩和检验,强脉冲光组和激光组疗效无显著差异,而联合组疗效显著好于强脉冲光组（Z=7.123, P=0.024）和激光组（Z=6.024, P=0.030）。3组患者治疗后均无出现色素沉着加重、色素脱失病等不良反应。强脉冲光组和激光组的满意度无显著差异,而联合组的满意度显著好于强脉冲光组（Z=7.361, P=0.029）和激光组（Z=6.831, P=0.027）。结论:强脉冲光联合Nd:YAG激光治疗黄褐斑是一种安全有效的治疗方法,值得临床推广。     

Release of recombinant human bone morphogenetic protein-2 from heterocyclic methacrylate polymer systems.

The release of recombinant human bone morphogenetic protein-2 (rhBMP-2) from three room temperature polymerising methacrylate systems has been studied. These all contained poly(ethyl methacrylate) powder, but the monomer liquids comprised, respectively, tetrahydrofurfuryl methacrylate (THFM), 90/10 THFM/hydroxyethyl methacrylate (HEMA), and 70/30 THFM/ HEMA. In all cases, rhBMP-2 was released, but the addition of 10% HEMA accelerated release (a nine-fold increase in diffusion coefficient); a further increase to 30% HEMA had no additional effect. For most of the release process, a diffusion process operated, although the early stages were not well defined. At the end of the 15 day period, the release, respectively, for the PEM/THFM, PEM:90/10 THFM/HEMA and PEM:70/30 THFM/HEMA systems was 596, 878 and 923 ng (i.e. up to 92% of the rhBMP-2 added).     

Spherulites primary nucleation in binary miscible blends of poly(ethylene oxide) with poly(methyl methacrylate)

The influence of composition on the primary nucleation process of poly(ethylene oxide) spherulites in the case of poly(ethylene oxide)/poly(methyl methacrylate) (PEO/PMMA) blends was investigated by optical microscopy and DSC. In the case of isothermally crystallized samples it was found that heterogeneous nucleation is depressed in the blends in comparison with plain PEO. This depression is caused by the dilution effect of PMMA. The self-seeding nucleation mode is also disturbed by the presence of PMMA in the blends. This is due to both the diluent effect and to the decrease of the PEO melting temperature. In the case of non-isothermally crystallized samples of PEO/PMMA blends an apparent increase of the nucleation density was observed. This observation is attributed to the fact that the growth rate is depressed in the blends: thus, at an earlier stage of crystallization, the volume in which the nuclei are free to develop (for a given crystallization condition) is larger.     

Contribution of hydrophobic/hydrophilic modification on cationic chains of poly(ε-caprolactone)-graft-poly(dimethylamino ethylmethacrylate) amphiphilic co-polymer in gene delivery

Nanoparticles (NPs) assembled from amphiphilic polycations have been certified as potential carriers for gene delivery. Structural modification of polycation moieties may be an efficient route to further enhance gene delivery efficiency. In this study two electroneutral monomers with different hydrophobicities, 2-hydroxyethyl methacrylate (HEMA) and 2-hydroxyethyl acrylate (HEA), were incorporated into the cationic poly(dimethylamino ethyl methacrylate) (PDMAEMA) side-chains of amphiphilic poly(ε-caprolactone)-graft-poly(dimethylamino ethylmethacrylate) (PCD) by random co-polymerization, to obtain poly(ε-caprolactone)-graft-poly(dimethylamino ethyl methacrylate-co-2-hydroxyethyl methacrylate) (PCD-HEMA) and poly(ε-caprolactone)-graft-poly(dimethylamino ethyl methacrylate-co-2-hydroxyethyl acrylate) (PCD-HEA). Minimal HEA or HEMA moieties in PDMAEMA do not lead to statistically significant changes in particle size, zeta potential, DNA condensation properties and buffering capacity of the naked NPs. However, the incorporation of HEMA and HEA lead to reductions and increases, respectively, in the surface hydrophilicity of the naked NPs and NPs/DNA complexes, which was confirmed by water contact angle assay. These simple modifications of PDMAEMA with HEA and HEMA moieties significantly affect the gene transfection efficiency on HeLa cells in vitro: PCD-HEMA NP/DNA complexes show a much higher transfection efficiency than PCD NPs/DNA complexes, while PCD-HEA NPs/DNA complexes show a lower transfection efficiency than PCD NP/DNA complexes. Fluorescence activated cell sorter and confocal laser scanning microscope results indicate that the incorporation of hydrophobic HEMA moieties facilitates an enhancement in both cellular uptake and endosomal/lysosomal escape, leading to a higher transfection efficiency. Moreover, the process of endosomal/lysosomal escape confirmed in our research that PCD and its derivatives do not just rely on the proton sponge mechanism, but also on membrane damage due to the polycation chains, especially hydrophobic modified ones. Hence, it is proved that hydrophobic modification of cationic side-chains is a crucial route to improve gene transfection mediated by polycation NPs.     

Molecularly engineered p(HEMA)-based hydrogels for implant biochip biocompatibility

The strategy of phospholipid-based biomimicry has been used to molecularly engineer poly(2-hydroxyethyl methacrylate) [p(HEMA)]-based hydrogels for improved in vitro and potential in vivo biocompatibility. Two methacrylate-based monomers, poly(ethylene glycol) (200) monomethacrylate (PEGMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC), were incorporated at varying mole fractions of 0.0-0.5 mol% PEGMA and 0-10 mol% MPC respectively, into 3 mol% tetraethyleneglycol diacrylate (TEGDA) cross-linked p(HEMA) networks. Upon hydration of these engineered hydrogels, a reduction in receding contact angle from 22+/-1.2 degrees for p(HEMA) to 8+/-2.7 degrees for p(HEMA) containing 0.5:10 mol% PEGMA:MPC was observed, reflecting the significant increase in surface hydrophilicity with increasing PEGMA and MPC content upon prolonged hydration. Hydrogels containing MPC showed a temporal increase in hydrophilicity following continuous immersion in DI water over 5 days. Hydrogels containing 0.5 mol% PEGMA and MPC in the range of 5-10 mol% displayed reduced protein adsorption when incubated with the common extracellular matrix proteins; fibronectin, collagen or laminin, producing up to 64% less protein adsorption compared to p(HEMA). Compositional optima for cell viability and proliferation established from two-factor Central Composite design analysis of human muscle fibroblasts cultured on these hydrogels suggest that those containing PEGMA between 0.3 and 0.5 mol% and MPC levels around 5-10 mol% exhibit desirable characteristics for implant material coatings-high viability (>80%) with low proliferation (<40%), confirming a lack of cytotoxicity.     

Photoreaktionen von Biscyclopentadienyltitandichlorid in einer monomerhaltigen polymethylmethacrylat-matrix

It could be demonstrated that methyl methacrylate (MMA) in a poly(methyl methacrylate) (PMMA)-matrix can be polymerized by photoinduction with titaniumbiscyclopentadienyl dichloride (titanocene chloride). The photoinduced polymerized portion of MMA consists practically only of isotactic PMMA. The differences in polymerization by irradiation with laser light and with monochromatic light of a mercury light source with the same wavelength are discussed.     

Polyethylene/hydrophilic polymer blends for biomedical applications

Polyethylene blends with poly(2-hydroxyethyl methacrylate) [poly(HEMA)] or poly(2,3-dihydroxypropyl methacrylate) [poly(DHPMA)] were prepared by swelling polyethylene with HEMA or 2,3-epoxypropyl methacrylate (EPMA) and by polymerization of the respective monomers. Poly(EPMA) in blends was hydrolysed to poly(DHPMA) with acetic acid. The blends had similar surface and bulk compositions. Swelling with water and surface wettability were proportional to the content of the hydrophilic component; at the same content the polyethylene/poly(DHPMA) blends appeared more hydrophilic than those of polyethylene/poly(HEMA). Thrombus formation in contact with blood examined ex vivo and in vivo was considerably slower on the blends than on unmodified polyethylene. The tests indicated optima in composition; the best biological response was achieved with the blends containing about 14% poly(HEMA) or 16% poly(DHPMA).     

Overexposure analysis of pulsed distributed feedback laser source

The goal of this study is to assess the risk of overexposure, when DFB dye laser is used for medical treatment in pulsed mode operation. Results of experimental study showing an unexpected rise of energy in pulses of distributed feedback dye laser (DFDL) output due to temperature phase gratings in dye cell during passively Q switched and mode-locked operation is reported. This unintended increase in the number of pulses, pulse duration, per pulse energy may cause side effects, when used for selective photothermolysis. To probe this phenomenon the most commonly used Rh6G dye was excited with 10-20 pulses of second harmonic of a passively Q switched and mode-locked Nd:yttrium-aluminum-garnet(YAG) laser. The outputs of DFDL and Nd:YAG laser were recorded by an Imacon-675 streak camera. The peak of DFDL output pulses was found delayed proportionally from the peak of the Nd:YAG pulses by more than an interpulse period of excitation laser. A computer program was used to simulate the experimentally measured results to estimate the thermal decay constants and energy retained by medium. The delay between peaks of Nd:YAG (input) and DFDL (output) pulses was found to vary from 10 to 14 ns for various cavity lengths. It was interesting to note that for smaller inter-pulse periods the effect of gradual gain buildup satisfied the threshold conditions for some of the pulses that otherwise cannot lase. This may lead to unintended increase in energy fluence causing overexposure-induced bio effects.     

Three-dimensional topographic scanning electron microscope and Raman spectroscopic analyses of the irradiation effect on teeth by Nd:YAG, Er: YAG, and CO(2) lasers

A three-dimensional analyzer installed in a scanning electron microscope was used to evaluate the morphology and surface roughness using noncontact profilometry. Observations were carried out on the enamel and dentin surface irradiated by three different lasers: Nd:YAG (wavelength 1.06 microm), Er:YAG (2.94 microm), and CO(2) (10.6 microm). Spectroscopic analysis was done by Raman spectroscopy for nonirradiated and laser-irradiated surfaces. The lasers were applied perpendicularly to vertically sectioned and polished human extracted caries-free molars. The tooth was sectioned at each cavity for cross-section analysis after laser irradiation. Irradiation by Nd:YAG and CO(2) lasers of the enamel surface showed an opaque white color, different from dentin where the surface turned black. The Er:YAG laser induced no changes in color of the dentin. Numerous cracks associated with thermal stress were observed in the CO(2) laser-irradiated dentin. Noncontact surface profile analysis of Er:YAG laser-irradiated enamel and dentin showed the deepest cavities, and direct cross-sectional observations of them showed similar cavity outlines. The CO(2) laser-irradiated dentin had the least surface roughness. Raman spectroscopic analysis showed that fluorescence from the laser-irradiated tooth was generally greater than from nonirradiated teeth. Bands in dentin attributed to organic collagen matrix were lost after Nd:YAG and CO(2) laser irradiation, and a broad peak due to amorphous carbon appeared. The Er:YAG laser-irradiated dentin showed no sign of a carbon band and had more suitable results for dental ablation. Noncontact surface profile analysis was effective to evaluate the structural change in the tooth in the microarea of study after laser irradiation.