兔胃,肝血管TH胶栓塞后周围组织的病理学改变

目的；了解ＴＨ胶栓塞血管后引起的周围组织的病理改变。方法：对兔胃，肝静脉栓塞后，分别于２４ｈ，４８ｈ，７２ｈ１周２周处死，对动物标本进行肉眼和光镜观察。结果：血管栓塞后局部血流停滞，淤血，缺氧，周围组织发生无菌性坏死及炎症，肝细胞变性坏死，肝内纤维组织及肝细胞的结节性增生，胃粘膜出血坏死，脱落形成溃疡，但这些损害较为局限，多可自行愈合，结论；提示在血管内栓塞治疗中，应严格掌握ＴＨ胶用量，控制栓塞范     

Synthesis,characterization and surface modification of low moduli poly(ether carbonate urethane)ureas for soft tissue engineering

Flexible scaffolds are of great interest in engineering functional and mechano-active soft tissues as such scaffolds might allow mechanical stimuli to transfer effectively from the scaffolds to cells during tissue development. Towards this end, we have developed a family of flexible poly(ether carbonate urethane)ureas (PECUUs) with a triblock copolymer poly(trimethylene carbonate)–poly(ethylene oxide)–poly(trimethylene carbonate) (PTMC–PEO–PTMC) or pentablock copolymers PTMC–PEO–PPO–PEO–PTMC (PPO, polypropylene oxide) as soft segments, linked by 1,4-diisocyanatobutane and putrescine. All of the PECUUs had low glass transition temperatures (<?46 °C). The PTMC–PEO–PTMC-containing PECUUs had low tensile strength and breaking strain. Replacing PEO with the similar length PEO–PPO–PEO resulted in highly flexible and soft PECUUs possessing breaking strains of 362–711%, tensile strengths of 8–18 MPa and moduli of 5.5–7.4 MPa at room temperature in air. Under aqueous conditions at 37 °C, these polymers remained flexible while their moduli were decreased to 3.4–4.0 MPa. PECUUs based on PTMC–PEO–PPO–PEO–PTMC were thermosensitive as the water content at 37 °C was lower than that at 4 °C. PECUU using PTMC–PEO–PTMC as a soft segment showed 30% weight loss over 6 weeks in PBS at 37 °C, while that using PTMC–PEO–PPO–PEO–PTMC as a soft segment had weight loss <6%. Degradation products were found to lack cytotoxicity. The mechanical stresses and moduli of PECUUs based on PTMC–PEO–PPO–PEO–PTMC were unchanged during the degradation. To enhance cell adhesion, PECUUs were surface modified with Arg-Gly-Asp-Ser (RGDS). Smooth muscle cell adhesion was 114% of tissue culture polystyrene for unmodified PECUU and >180% for RGDS-modified PECUUs, with cell viability on both surfaces increasing during culture. These low moduli polyurethanes may find applications in engineering cardiovascular or other soft tissues.     

Synthesis and characterization of fluorocarbon chain end-capped poly(carbonate urethane)s as biomaterials: a novel bilayered surface structure

Poly(carbonate urethane)s (PCUs) are usually considered as biostable elastomers for long-term implantation. However, their hydrolytic stability is still questionable. The biodegradation appears to be initiated by oxidative and hydrolytic substances released by inflammatory cells. Therefore, the biostability of polyurethane might be improved with control of surface structure to reduce inflammatory response. A new type of PCUs end-capped with perfluoro chains was synthesized to explore a new avenue. A fluorinated alcohol, 2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluoro-1-octanol (PDFOL), was end-capped to the backbones of PCUs by reaction of the --OH in PDFOL with the --NCO end groups in PCU backbones. Contact angle measurement, X-ray photoelectron spectroscopy, atomic force microscopy, and attenuated total reflectance-Fourier transform infrared spectroscopy were used to examine their surface structure and properties. Elemental analysis, gel permeation chromatography, differential scanning calorimetry, and tensile testing were used to assess bulk chemistry and properties. The fluorocarbon end-capped poly (carbonate urethane)s (FPCUs) maintained the high mechanical properties (about 40 MPa tensile strength) and typical microphase separation structure of polyurethane elastomers. Results from surface analyses revealed the presence of a double-layered structure at the surfaces of the FPCUs. The first one was composed of fluorocarbon tails rising up on the uppermost layer and the second one made up of hard-segments. This novel bilayered surface structure could protect the weak carbonate linkages in soft segments, and consequently, may potentially increase the biostability of this kind of polyurethanes.     

小口径医用聚氨酯人造血管径向顺应性研究

目的 比较小口径医用聚氨酯人造血管在干法制作与湿法制作方法下的微观形态和径向顺应 性,探讨管径大小、管壁厚度对血管顺应性的影响,分析接枝血管中不同部位的顺应性差别。 方法 通过在玻璃棒模具上复合均匀厚度的聚氨酯膜,制作出小口径聚氨酯人造血管。在自 行搭建的顺应性测试回路装置中测试得到压力与直径的关系,依据ISO7198国际标准计算 出人造血管的径向顺应性。结果 干法制作的聚氨酯人造血管表面与截面均很致密,湿法制 作的聚氨酯人造血管的截面呈微孔结构;随着人造血管管径的增大,顺应性逐渐增大;随着 管壁厚度的增加,顺应性逐渐减小;人造血管的接口处的径向顺应性波动较中间处大;湿法 制作的人造血管顺应性要优于干法制作的人造血管顺应性。结论：医用聚氨酯制作的小口径 人造血管具有良好的径向顺应性,是很有前景的小口径血管代用品材料;影响顺应性不匹配 的因素有很多,还需做进一步的研究。     

三丙烯微球栓塞子宫动脉对子宫内膜血管的影响

背景：子宫动脉栓塞已广泛应用于临床治疗多种妇产科疾病,但对于子宫动脉栓塞后子宫内膜微血管密度的有何变化及新生血管的形成至今少有文献报道。 目的：观察子宫动脉栓塞对子宫内膜微血管密度及新生血管形成的影响。 方法：60只雌性豚鼠随机分为对照组(n=15)及子宫动脉栓塞组(n=45),子宫动脉栓塞组动物应用三丙烯微球行双侧子宫动脉栓塞。子宫动脉栓塞组再随机分为E1,E2及E3三个亚组(n=15),分别于子宫动脉栓塞后7-15 d,16-30 d及31-45 d内获取子宫标本。 结果与结论：常规病理染色显示豚鼠子宫动脉一级分支、浆膜下动脉支及子宫肌层微小动脉血管内均可见大小不等栓塞微球分布。子宫动脉栓塞豚鼠子宫内膜基底层微血管密度CD34在子宫动脉栓塞后降低,而后随时间的延长而增加(P < 0.05);而子宫动脉栓塞豚鼠子宫内膜基底层微血管密度CD105在子宫动脉栓塞后增加,而后随时间的延长而降低(P < 0.05)。提示随着栓塞后时间推延,新生微血管数量显著增加,基底层微血管密度有逐渐恢复趋势。     

PEGylation of microspheres for therapeutic embolization: preparation, characterization and biological performance evaluation

In this study, microspheres designed for embolization, defined as GF2000-Trisacryl MS (GF-MS) and DEAE-Trisacryl MS (DEAE-MS), were originally PEGylated using (3-amino propyl) triethoxy silane as coupling agent. Indomethacin was loaded into both PEGylated and non-PEGylated DEAE-MS, displaying ion-exchange ability, through a batch process with a respective capacity of 1.2 and 0.25 g/g. The morphology of naked and PEGylated MS was evaluated by scanning electron microscopy (SEM). Both micosphere resins surface looked like orange skin, although DEAE-MS showed a slightly rougher surface due to the copolymerization process. PEGylated microspheres have a most likely swelling surface owing to the presence of PEG hydrophilic chains. The mean diameters were of about 66 and 60 microm for GF-MS and DEAE-MS, respectively. Data obtained for PEGylated MS by Fourier Transform Infrared spectroscopy (FTIR) confirmed that microspheres were successfully PEGylated. Finally, complement activation in vitro was performed to evaluate the activating capacity of different microspheres. Both PEGylated GF-MS and DEAE-MS activated the complement system of about 33% less than their corresponding naked microspheres, while loading PEGylated DEAE-MS with indomethacin almost suppressed complement activation. This inhibiting role implies that PEGylation as well as loading the microspheres with anti-inflammatory drug has a compact effect on the interaction of microspheres with blood proteins.     

Synthesis and characterization of poly(ethylene oxide) and poly(perfluorohexylethyl methacrylate) containing triblock copolymers

A new series of poly(perfluorohexylethyl methacrylate)‐block‐poly(ethylene oxide)‐block‐poly(perfluorohexylethyl methacrylate), PFMA‐b‐PEO‐b‐PFMA triblock copolymers has been synthesized by atom transfer radical polymerization using bifunctional PEO macroinitiators. The molecular structure of the block copolymers was confirmed by ¹H NMR spectroscopy and SEC. X‐ray scattering studies have been carried out to investigate their bulk properties. SAXS has shown cubic arrangement of spheres (bcc), hexagonally packed cylinders (hpc) and lamellar microdomain formation in the melt of triblock copolymers investigated, depending on composition. Crystallization was, however, found to destroy the ordered melt morphology and imposes a lamellar crystalline structure. WAXS, DSC and polarized light microscopy measurements confirmed the crystallization of PEO segments in block copolymers. Long PFMA blocks were found to have significant effect on PEO crystallization.

Synthesis of triblock copolymers of EO and FMA by ATRP.     

Increased proliferation activities of vascular endothelial cells and tumour cells in residual hepatocellular carcinoma following transcatheter arterial embolization

AIMS: Transcatheter arterial embolization induces extensive ischaemic necrosis or hypoxia via the obstruction of the hepatic artery in hepatocellular carcinoma (HCC). Ischaemia is strongly correlated with an increased expression of angiogenic factor and stimulates an increase in angiogenesis, including endothelial cell proliferation. The aim of this study was to evaluate whether ischaemic necrosis induced by transcatheter arterial embolization could increase the proliferative activities of intratumoral endothelial cells or tumour cells in the residual HCC. METHODS AND RESULTS: Using a double immunohistochemical technique (Ki67 antibody to determine the proliferative activity and CD34 antibody to highlight the intratumoral endothelial cells), we performed immunohistochemical staining for 24 HCCs treated by transcatheter arterial embolization. Seven HCCs without any preoperative transcatheter arterial embolization and nine cirrhosis cases were also studied as the control cases. The residual tumour was then divided into five areas at 0.5 mm intervals, according to the distance from the necrotic margin induced by embolization. The Ki67 labelling indices of the intratumoral endothelial cells and tumour cells were counted in each area. The correlation between the indices and the corresponding distance from the ischaemic necrosis was analysed. The Ki67 labelling index of intratumoral vascular endothelial cells in the area less than 0.5 mm from the necrotic margin (area 1) was 10.60 +/- 3.64% (mean +/- SD), which was twofold greater than those of the other areas more than 0.5 mm from the margin (areas 2--5) and those of the control HCCs without preoperative transcatheter arterial embolization. In addition, the proliferation labelling index of the tumour cells was 35.77 +/- 11.45% (mean +/- SD) in area 1. This was higher than those of areas 2--5 and control HCCs without preoperative transcatheter arterial embolization. There was a positive correlation between the proliferation of both endothelial and tumour cells and ischaemic necrosis (P < 0.05). CONCLUSIONS: Our study suggests that the proliferative activity of intratumoral endothelial cells and tumour cells is increased by ischaemic necrosis induced by transcatheter arterial embolization, and its effect is maximal in the area adjacent to the necrosis (less than 0.5 mm from the necrotic margin).     

Synthesis and characterization of polycaprolactone / poly(ethylene oxide) / polylactide tri-component copolymers

Polycaprolactonel/poly(ethylene oxide)/polylactide tri-component copolymers (PCEL) with different compositions were synthesized by copolymerization of ε-caprolactone and L-lactide in the presence of poly(ethylene glycol) using stannous octoate as a catalyst. The copolymers were purified and characterized by various analytical techniques such as GPC, FT-IR, H NMR, ¹³C NMR, DSC, and X-ray diffractometry. It was evidenced that these copolymers were pure tri-component compounds which exhibited partially random chain structures, and possessed good mechanical properties and variable biodegradability.     

Modification of poly(ether urethane)elastomers by incorporation of poly(isobutylene)glycol. Relation between polymer properties and thrombogenicity

Non-polar hydrophobic poly(isobutylene)glycol (PIBG) was substituted for poly(tetramethylene ether)glycol (PTMEG) in poly(ether urethanes) based on 4,4'-methylenebis-(phenylisocyanate) (MDI) and 1,4-butanediol (BD) as chain extender. Two series of polyurethanes differing in their soft segment length, polymer composition, and hard segment content were studied by dynamic mechanical analysis (DMA) and static, as well as dynamic, contact angle measurements. The thrombogenicity of these polymers was characterized by studying the adhesion and activation of platelets using ELISA for GMP 140 and fluorescence microscopy. It was found by DMA that in PIBG-containing polyurethanes (PUE) exist soft domains containing hard segments, strictly separated hard segment domains, and hard segments partially mixed with soft segments. Contact angle measurements revealed that 25% PIBG or even less, are sufficient for a remarkable enrichment of these non-polar soft segments on the polymer surface. The platelet adhesion/activation on these materials was demonstrated to increase with the rise in hard segment content, as well as with an enhancement of the PIBG content. However, comparison of PIBG-containing PUE with medical applied polypropylene and pellethane expressed that PUE with PIBG content equal or less 25% have excellent haemocompatibility.     

载羟基喜树碱聚乳酸-羟基乙酸微球的制备及相关性能研究

目的制备一种载羟基喜树碱的聚乳酸-羟基乙酸(PLGA)缓释微球,并考察其相关性能。方法采用乳化-溶剂挥发法制备羟基喜树碱PLGA微球,用扫描电子显微镜观察载药微球表面形态,测定平均粒径及跨距,高效液相色谱检测包封率、载药率及体外释放情况,改良寇氏法计算小鼠半数致死量。结果制备的载药PLGA微球呈圆球形,表面光滑,无粘连,平均粒径30.8μm,跨距0.9,包封率为85.5%、载药率4.28%,在体外28 d累积释放药物81.4%。羟基喜树碱小鼠静脉注射的半数致死量为18.4 mg/kg,肌内注射半数致死量为71.3 mg/kg,而羟基喜树碱PLGA微球肌内注射的半数致死量为138.5 mg/kg。结论乳化-溶剂挥发法制备的羟基喜树碱PLGA微球粒径适宜,包封率、载药率高,缓释效果好,毒性低,具有潜在的临床应用价值。     

Synthesis and characterization of putrescine-based poly(phosphoester-urethanes)

A novel set of putrescine-based segmented polyurethanes was synthesized using 1,4-butane-diisocyante and phosphoester diols, and was characterized for its potential as a degradable biomaterial. These poly(phosphoester-urethanes) (PPU) were flexible polymers with ultimate tensile strength (UTS) from 2 to 3 MPa, elongations up to 80% and tan δ near 0.15. The incorporation of phosphoester bonds in the backbone of the polymer by using bis(2-hydroxyethyl)phosphite (BGP) and bis(6-hydroxyhexyl)-phosphite (BHP) as chain extenders resulted in hydrolytic degradation which was evaluated in vitro. By varying the content of the phosphoester diol BGP, degradation rate, as followed by mass loss and GPC, could be modulated. Polymers based on the more hydrophobic monomer, BHP, showed slower degradation than corresponding BGP based polymers. Tensile properties of PPU-B2 after 22 days in vitro degradation show more than a 50% drop in UTS and ultimate elongation, likely caused by void spaces left behind in the polymer after mass loss and swelling. The attachment of a drug, PAS, pendant to the phosphoester group of the PPU was demonstrated. PAS was linked via the spacer 4-hydroxybenzaldehyde, and free, intact drug was released in about 5 h from a thin film.     

Preparation and characterization of Japanese encephalitis virus vaccine loaded poly(L-lactide-co-glycolide) microspheres for oral immunization.

Japanese encephalitis virus (JEV) vaccine loaded biodegradable poly(L-lactide-co-glycolide) (PLGA) microspheres (MSs) were prepared by W/O/W solvent evaporation method to study the possibility for oral vaccination. The influence of several preparation parameters as stirring rate, types and concentration of emulsifier, PLGA concentration, etc. has been observed on size, size distribution and biodegradation. The mean MSs size decreased when the agitation speed and the concentration of emulsifier were increased, and when the PLGA concentration was decreased. The surface morphology of porous and nonporous JEV vaccine loaded PLGA MSs was prepared from polyvinylalcohol and sodium dodecyl sulfate as used emulsifiers, respectively. From the assay of lactic acid and scanning electron microscope observation, it can be suggested that the rate of biodegradation of nonporous MSs was slower than that of porous surface morphology due to lower the surface area. Mechanisms of the formation of porous and nonporous surface by different types of emulsifier, and the biodegradation of MSs have been proposed. Also, the size and size distribution of JEV vaccine loaded PLGA MSs were discussed to apply oral vaccination through the Peyer's patches across the gastrointestinal tract.     

Novel diazosulfonate terpolymers for the preparation of structured functionalized surfaces: Synthesis and characterization

We report the synthesis and characterization of novel diazosulfonate copolymers and terpolymers by free‐radical polymerization for the preparation of ultrathin films. Such films were covalently linked to silicon and glass substrates after a spin‐coating and annealing process using 3‐(trimethoxysilyl)propyl methacrylate as the adhesive comonomer. The polymers were characterized by NMR and IR spectroscopy and ellipsometry, and contact‐angle measurements were used to analyze the film properties. The light‐sensitive but thermally stable polymer films can be structured successfully by UV light down to the micrometer scale. The patterns written into the diazosulfonate film were produced by a UV laser without a mask. The photolysis in solution and in film was examined by UV spectroscopy.

UV imaging: area selective representation of the UV transmission between 430 and 450 nm over a 60 × 60 μm² area of a spin coated film of copolymer 2 . Pre‐structuring with a He‐Cd laser (at 325 nm) resulted in a ring‐shaped structure of 30‐μm diameter showing a higher transmissivity (brighter area) resulting from the reduced absorption of the polymer film (decomposition of the diazosulfonate functions).     

Preparation and structure of drug-carrying biodegradable microspheres designed for transarterial chemoembolization therapy

Biodegradable poly(D,L-lactic acid) drug-eluting microspheres containing anti-tumor drugs, cisplatin, and sorafenib tosylate have been prepared by the emulsion solvent evaporation method with diameter between 200 and 400 μm. Scanning electron microscopy showed that cisplatin microspheres had smooth surfaces, while sorafenib tosylate microspheres and cisplatin + sorafenib tosylate microspheres were porous at the surface and the pits of the latter were larger than those of the former. Notably, cisplatin + sorafenib tosylate microspheres had a fast drug release rate compared with microspheres containing one drug alone. In vitro cytotoxicity experiments and classical matrigel endothelial tube assay certificated the maintaining bioactivity of cisplatin and sorafenib tosylate released from the microspheres, respectively. This work provides a useful approach for the fabrication of drug-eluting beads used in transarterial chemoembolization.     

Synthesis and characterization of uniform radiopaque polystyrene microspheres for X-ray imaging by a single-step swelling process

Uniform radiopaque polystyrene microspheres of approximately 2.3 +/- 0.2 microm were prepared by a single-step swelling of 2.3 +/- 0.2 microm polystyrene template microspheres, dispersed in an aqueous solution with methylene chloride emulsion droplets containing 2,3,5-triiodobenzoylethyl ester. After completing the swelling process, the methylene chloride was evaporated in order to lock the 2,3,5-triiodobenzoylethyl ester in the polystyrene microspheres. The influence of the weight ratio [2,3,5-triiodobenzoylethyl ester]/[polystyrene] on the % of entrapped 2,3,5-triiodobenzoylethyl ester was elucidated. Characterization of the radiopaque polystyrene microspheres was accomplished by light microscope, FTIR, TGA, SEM, XPS, and elemental analysis. The radiopacity of the microspheres was demonstrated by an imaging technique based on X-ray absorption usually used in hospitals. This novel method of encapsulation of 2,3,5-triiodobenzoylethyl ester within polystyrene microspheres by a single-step swelling process may be used as a model for encapsulation of various hydrophobic radiopaque drugs within uniform polystyrene template particles of various diameters for different X-ray imaging needs, e.g., blood pool, body organs, embolization, dental composition, implants, protheses, and nanocomposites.     

Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microspheres for the sustained release of 5-fluorouracil

Biodegradable microspheres were prepared with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV, 85:15 by mole ratio of hydroxybutyrate to hydroxyvalerate) by an water-in-oil-in-water (W/O/W), oil-in-water (O/W) and oil-in-oil (O/O) solvent evaporation method for the sustained release of anti-cancer drug, 5-fluorouracil (5-FU) with controlling the fabrication conditions. The shape of microspheres prepared was relatively rough due to highly crystalline property of PHBV and spherical. The efficiency of 5-FU loading into the PHBV microsphere with O/O method was over 80% compared to that 7% for microspheres by O/W method and below 1% for microspheres by a conventional W/O/W method. However, the most desirable release pattern can be achieved from the O/W method due to the cosolvent effect. The effects of preparation conditions such as the type and amount of surfactant, initial amount of loaded drug, the temperature of solvent evaporation, and etc. on the morphology for W/O/W method were investigated. Possible mechanisms of the desirable sustained release pattern for O/W system have been proposed.     

Mechanical property characterization of electrospun recombinant human tropoelastin for vascular graft biomaterials

The development of vascular grafts has focused on finding a biomaterial that is non-thrombogenic, minimizes intimal hyperplasia, matches the mechanical properties of native vessels and allows for regeneration of arterial tissue. In this study, the structural and mechanical properties and the vascular cell compatibility of electrospun recombinant human tropoelastin (rTE) were evaluated as a potential vascular graft support matrix. Disuccinimidyl suberate (DSS) was used to cross-link electrospun rTE fibers to produce a polymeric recombinant tropoelastin (prTE) matrix that is stable in aqueous environments. Tubular 1 cm diameter prTE samples were constructed for uniaxial tensile testing and 4 mm small-diameter prTE tubular scaffolds were produced for burst pressure and cell compatibility evaluations from 15 wt.% rTE solutions. Uniaxial tensile tests demonstrated an average ultimate tensile strength (UTS) of 0.36 ± 0.05 MPa and elastic moduli of 0.15 ± 0.04 and 0.91 ± 0.16 MPa, which were comparable to extracted native elastin. Burst pressures of 485 ± 25 mm Hg were obtained from 4 mm internal diameter scaffolds with 453 ± 74 μm average wall thickness. prTE supported endothelial cell growth with typical endothelial cell cobblestone morphology after 48 h in culture. Cross-linked electrospun rTE has promising properties for utilization as a vascular graft biomaterial with customizable dimensions, a compliant matrix and vascular cell compatibility.     

Synthesis, characterization, and in vitro 5-Fu release behavior of poly(2,2-dimethyltrimethylene carbonate)-poly(ethylene glycol)-poly(2,2-dimethyltrimethylene carbonate) nanoparticles

Novel ABA-type amphiphilic triblock copolymers composed of poly (ethylene glycol) (PEG) as hydrophilic segment and poly (2,2-dimethyltrimethylene carbonate) (PDTC) as hydrophobic segment were synthesized by ring-opening polymerization of 2,2-dimethyltrimethylene carbonate (DTC) initiated by dihydroxyl PEG. The influence of introducing PEG block on crystalline behavior of PDTC segment was investigated by DSC. Polymeric micelles in aqueous medium were characterized by fluorescence spectroscopy and dynamic light scattering. The critical micelle concentration of these copolymers was in the range of 5.1-50.5 mg/L. Particle size was 80-280 nm. Core-shell-type nanoparticles were prepared by the dialysis technique. Zeta potential was measured by laser Doppler anemometry, and all nanoparticles had negative zeta potential. Transmission electron microscopy images demonstrated that these nanoparticles were spherical in shape. Anticancer drug 5-fluorouracil (5-Fu) as a model drug was loaded in the polymeric nanoparticles. X-ray powder diffraction demonstrated that 5-Fu was encapsulated into polymeric nanoparticles as molecular dispersion. In vitro cytotoxicity of nanoparticles was evaluated by MTT assay. In vitro release behavior of 5-Fu was investigated, and sustained drug release was achieved.