温敏型壳聚糖/甘油磷酸钠缓释胰岛素凝胶系统的制备

目的:初步探讨制备温敏性壳聚糖/甘油磷酸钠载胰岛素凝胶系统.方法:应用壳聚糖与甘油磷酸钠制备具有温敏性的载有胰岛素的凝胶体系,从凝胶体系的pH值、粘度测定、胶凝时间研究不同配比、不同pH值对壳聚糖/甘油磷酸钠(CS/β-GP) 体系凝胶化性能的影响.结果:壳聚糖凝胶在室温(25℃)下呈液态,56% 甘油磷酸钠(β-GP)与3%壳聚糖(CS)在pH值6.8-7.2,37℃下凝胶化时间(GT) 从1h缩短到8-12min,凝胶形态良好,并且在负载胰岛素溶液后C/GP凝胶形态未受影响.结论:一定配比CS/GPS 体系在37℃具有快速凝胶化性能,在加入胰岛素后并未改变其温敏特性,为后续的温敏性壳聚糖/甘油磷酸钠载胰岛素凝胶系统的体外释药实验打下了基础.     

新型壳聚糖基引导骨再生膜的蛋白缓释性能研究

目的：制备负载牛血清白蛋白的壳聚糖/β-甘油磷酸钠(CS/β-GP)可吸收性膜,探讨其缓释蛋白的性能。方法：利用CS/β-GP体系的温敏相转变特性,同时向其中添加蛋白制成新型生物膜。进行膜厚度及拉伸强度等力学性能测试。利用BCA蛋白浓度试剂盒（加强型）检测不同时点的蛋白浓度,绘制膜的蛋白缓释曲线。结果：利用SPSS16.0统计分析软件进行分析,负载蛋白后复合膜的理化性能均未发生明显变化（P>0.05）。不同浓度的复合膜可缓慢释放蛋白12天以上,并且随着β-GP浓度的升高,蛋白缓释总量增大。结论：新型壳聚糖温敏凝胶膜可以作为蛋白缓释的载体,是在引导骨再生领域具有应用潜力的生物膜材料。     

两种消毒方式对壳聚糖水凝胶温敏性能及模型蛋白体外缓释性能的影响

目的探索两种消毒方式对壳聚糖水凝胶温敏性能及缓释性能的影响,为壳聚糖水凝胶临床应用前消毒方式的选择提供依据。 方法在制备壳聚糖温敏水凝胶前,采用两种方式进行消毒处理。（1）传统组：高压蒸汽消毒壳聚糖-醋酸溶液;（2）改良组：高压蒸汽消毒壳聚糖粉末。检测两组凝胶的成胶时间、旋转粘度;扫描电镜观察表面及截面形貌;傅立叶红外光谱检测特征性吸收峰;采用牛血清白蛋白（BSA）作为模型蛋白,观测体外缓释性能;SDS-PAGE检测缓释后的蛋白完整性。结果采用两独立样本的t检验进行统计。 结果37℃时,传统组成胶时间明显长于改良组（t= 61.677,P= 0.000）;改良组的旋转粘度在37℃时达15 000 mPa.s,传统组37℃时粘度为1560 mPa.s,40℃时上升至11 500 mPa.s;两组凝胶表面致密完整,截面均呈三维立体网状多孔结构,传统组孔隙大于改良组;两实验组与未消毒壳聚糖的吸收光谱基本一致;两组均有良好的缓释性能,改良组缓释性能更佳（t= 61.415,P= 0.000）,且释放出的模型蛋白分子结构完整。 结论采用改良消毒方式的壳聚糖水凝胶成胶时间更短,温敏性能更佳,缓释性能良好,且与传统组一样能保持缓释蛋白结构完整性。     

黄芩苷和重组人骨形成蛋白2双缓释制剂促进小型猪牙周组织再生的初步研究

目的:研究黄芩苷和重组人骨形成蛋白2双缓释制剂联合应用对小型猪牙周组织的再生作用。方法:建立小型猪牙周炎动物模型,随机分为4组。双缓组——壳聚糖温敏凝胶+重组人骨形成蛋白液(rhBMP-2)+黄芩苷-明胶微球(GMS),单黄组——壳聚糖温敏凝胶+黄芩苷-GMS,BMP组——壳聚糖温敏凝胶+rhBMP-2液,阴性对照组——空白凝胶。在建模前、后6周,治疗后4周和8周检查牙周病的相关临床指标,龈沟液IL-1β、TNF-α的变化。采用SPSS13.0软件包对数据进行统计学分析,并于治疗后8周进行组织学观察。结果:(1)各组在治疗4周、8周后,临床检查指标及龈沟液IL-1β、TNF-α检查水平与建模6周相比均有显著差异(P<0.05);双缓组治疗效果优于其他各组(P<0.05),且各项指标呈持续改善状态。X线片显示,治疗8周后,与对照组相比,其他3组骨密度及牙槽骨高度都有所增加,其中,双缓组骨密度及高度增加最为显著。(2)组织学改变:治疗8周后,阴性对照组牙周组织炎症反应明显,无明显修复反应;其他3组可见不同量的新生骨质。其中,双缓组牙周组织炎症程度较对照组明显减轻,修复反应最为明显。结论:黄芩苷和rhBMP-2联合应用能更好地促进牙周组织再生,为黄芩苷和rhBMP-2双缓释体系的临床应用奠定了基础。     

骨形成蛋白和氯己定双缓释的壳聚糖温敏凝胶用于牙周组织再生的实验研究

目的 观察双重缓释骨形成蛋白和氯己定的壳聚糖温敏载药凝胶修复牙周组织缺损的效果.方法 制备犬前磨牙Ⅱ度根分叉牙周组织缺损模型,分5组于牙周组织缺损处分别注入:①自制的双重缓释骨形态发生蛋白和氯己定的载药凝胶(T1组);②仅加载缓释骨形态发生蛋白的壳聚糖温敏凝胶(T2组);③仅加载缓释氯己定的壳聚糖温敏凝胶(T3组);④未加载任何药物的壳聚糖温敏凝胶(C1组);⑤不注射任何载体及药物(C0组).术后不使用抗生素,常规护理,8周后取材进行大体及组织学观察牙龈炎性反应及牙周组织再生情况.结果 应用壳聚糖温敏凝胶,可以方便地通过注射方式局部安放载体.T1组新生牙槽骨高度平均达到缺损高度的99.2%,T2组新生牙槽骨高度平均达到缺损高度的87.8%,T3组为63.6%,C1组为37.0%,CO组为34.3%;牙龈炎性反应细胞浸润情况显示T1及T3组炎细胞数量明显少于其他组.结论 自制双缓释壳聚糖温敏凝胶有效发挥了骨形态发生蛋白和氯己定各自的作用,并且在牙周组织再生治疗中具有简便性和有效性.     

壳聚糖温敏凝胶膜的制备及其生物活性初步研究

目的：制备壳聚糖/β-甘油磷酸钠（CS/β-GP）温敏凝胶新型可吸收性引导组织再生膜,通过体外细胞培养初步评价其生物相容性。方法：利用（CS/β-GP）体系的温敏相转变特性,合成温敏凝胶膜,并通过FTIR、SEM对膜的结构进行表征。MTT比色法对体外共培养的小鼠成纤维细胞（L929cell）的生长及增殖情况进行初步评价。结果：壳聚糖与β-甘油磷酸钠分子间存在静电作用和化学键结合,最终形成了新的复合生物膜,且具有多孔的表面结构和内部结构。MTT比色法显示与L929细胞体外共培养第3、4、5d,以生物膜为实验组的吸光度（A）值明显高于空白对照组,组间有统计学差异（P〈0.01）。结论：壳聚糖/β-甘油磷酸钠温敏凝胶膜具有多孔结构和良好的生物活性,能促进成纤维细胞的体外增殖,作为一种新型引导组织再膜具有良好的应用前景。     

缓释人富血小板血浆生长因子壳聚糖微球的制备

目的：制备载人富血小板血浆（hPRP）生长因子壳聚糖微球,观察其体外缓释效果。方法：选用离子凝胶法制备壳聚糖微球,利用微球吸附hPRP生长因子;以微球对hPRP中主要生长因子TGF-β1的吸附率作为评价指标,优化微球制备配方,并观察优化配方微球体外缓释TGF-β1效果;以hPRP中PDGF-AB为对象考察优化配方微球对其吸附率、载生长因子率,验证微球吸附效果。结果：当壳聚糖溶液浓度为2.5mg/ml、10mg/ml多聚磷酸钠溶液滴加量为2.5ml时可获得优化的壳聚糖微球制备配方。优化配方微球对hPRP中主要生长因子TGF-β1、PDGF-AB吸附率分别为78.02%、58.28%,载生长因子率分别为3.70ng/mg、1.31ng/mg;载hPRP生长因子的微球体外21天缓释TGF-β1累计35.80ng,占吸附总量的85.52%。结论：本实验制备的壳聚糖微球可初步实现吸附hPRP复合生长因子,并初步达到体外缓释效果。     

盐酸米诺环素微球凝胶的制备及对大鼠实验性牙龈炎的抑制作用

目的:制备含盐酸米诺环素微球的功能性壳聚糖温敏凝胶,并观察载药凝胶对大鼠牙龈炎模型的抑菌效果。方法:将小分子药物盐酸米诺环素先制备成微球,共混于温敏凝胶中,观察其理化性质及释药性能;建立大鼠的实验性牙龈炎模型,观察载药凝胶对实验性牙龈炎模型的消炎效果。结果:实验制得的缓释凝胶,T50%可延长至4.24d;动物实验初步结果显示,与对照组相比实验组的牙龈指数和探诊深度有明显的减少,炎症细胞浸润数量少,毛细血管扩张程度轻。结论:加载盐酸米诺环素的缓释凝胶对大鼠实验性牙龈炎有一定的消炎作用。     

高温高压对壳聚糖／甘油磷酸钠温敏凝胶释药性能的影响

目的：研究高温高压后的壳聚糖／甘油磷酸钠凝胶温敏、释药性能。方法：观察不同比例的壳聚糖和甘油磷酸钠混合液的凝胶时间、pH值变化。粘度测试比较不同比例壳聚糖／甘油磷酸钠混合液粘度变化。在37℃形成凝胶后,观察该体系作为奥硝唑药物模型载体的释药性能。结果：随着壳聚糖／甘油磷酸钠混合液中甘油磷酸钠的比例增加,溶液pH值增加,在37℃下,壳聚糖／甘油磷酸钠凝胶时间缩短,但当壳聚糖／甘油磷酸比例为2：1、1：1时,溶液不凝胶。粘度实验表明,4种比例（9：1、8：1、7：1、6：1）壳聚糖／甘油磷酸溶液随着时间增加,粘度明显增加,到10 min后粘度基本不变化,9：1比例组粘度最大为（53±0．9）Pa·s。药物释放实验表明,以奥硝唑为释药模型,该凝胶可持续释放200 min以上。结论：改进消毒方法后的壳聚糖／甘油磷酸钠,增加甘油磷酸钠比例可以提高溶液pH值,可在37℃下快速形成凝胶。该凝胶具有温敏性,具有缓慢释放药物能力。     

复合重组人骨形态发生蛋白-2缓释微球的引导组织再生膜的制备

目的设计制备包含活性生长因子的引导组织再生生物膜(以下称功能性复合膜)。方法利用天然材料右旋糖酐(dextran,dex)合成甲基丙烯酸缩水甘油酯右旋糖酐(dextran-glycidylmethacrylate,dex-GMA)作为重组人骨形态发生蛋白-2(recombinedhumanbonemorphogeneticprotein-2,rhBMP2)新型缓释载体,采用乳化交联技术制备dex-GMA凝胶微球,考察其形态、溶胀系数、载药、释药及降解性能;以壳聚糖为材料,复合载rhBMP2的dex-GMA凝胶微球制备生物膜并对其进行生物学评价。结果dex-GMA在一定条件下可以成球;该凝胶微球溶胀、载药和降解性能良好,体外释药可达20d以上,利用简单的工艺就可以制备复合rhBMP2缓释载体的功能性复合膜,其理化性能与没有复合该缓释载体的生物膜没有变化。结论利用生长因子缓释载体可以制备功能性复合膜,其生物学性能有待进一步研究。     

定量缓释基因重组碱性成纤维细胞生长因子／聚乳酸-聚羟基乙酸植入片的制备及体外释药研究

目的制备基因重组碱性成纤维细胞生长因子／聚乳酸-聚羟基乙酸（rbFGF／PLGA）定量缓释植入片，观察其一般性质、体外释药特性和rbFGF生物活性维持情况。方法溶剂挥发法制备rbFGF／PLGA植入片，用ELISA双抗体夹心法测定植入片中rbFGF含量，进行体外释药试验，检测rbFGF释放速度和含量，并将植入片植入兔下颌牵张成骨区局部缓慢释放观察rbFGF活性。结果rbFGF／PLGA植入片表面光滑平整，质地均匀，rbFGF含量为3.613μg／片。标准曲线方程为C=1280，54A-99.21（n=7，r^2=0.9952），线性范围15.6，1000pg／ml。植入片体外第1天释放rbFGF 10.70％，第9天累积释放51％，第20天释放达到80％以上。兔下颌牵张成骨实验结果显示植入组新骨形成速度和质量均优于对照组。结论rbFGF／PLGA植入片制备工艺良好，植入片中rbFGF生物活性保存良好，具有定量缓释作用并能促进牵张成骨中新骨形成的速度和质量。     

甲硝唑缓释牙胶尖的制备及体外释放实验

目的:研制一种用于根管消毒的甲硝唑缓释系统,测定其体外持续释放有效药物浓度的时间。方法:选择牙胶尖为载体,吸附甲硝唑等制备成药尖,聚乙二醇-1500与醋酸纤维素分别按不同比例混合作缓释膜,制成4组甲硝唑缓释牙胶尖(SRDGM),根据4组缓释剂的体外释放度及相应参数,选择释放甲硝唑有效药物浓度时间最长的一组作为实验用的缓释剂。选8颗单根管离体牙,SRDGM作根管消毒剂,紫外分光光度法测定体外释放度。结果:SRDGM含甲硝唑2013μg,24h释出全部药量的68.24%。SRDGM在离体牙根管内持续释放有效药物浓度达10d以上,第10天释出药物浓度33.13μg/ml,超过甲硝唑的最低抑菌浓度。结论:本研究研制的SRDGM可以载送药物,并控制释放;能在根管内维持一定时间的有效药物浓度达10d以上,防止根管再感染。     

Fluoride release and uptake by glass ionomers

Abstract – The aim was to study the fluoride release 1) from 7 and 15-month-old glass ionomer specimens after treating them with fluoride; 2) from fresh compared with matured material; and 3) from specimens stored for 29 months in running water. Glass ionomer test specimens which had been in running water for first 7 then 15 months were treated with a 50 ppm fluoride solution after which the specimens were again exposed to running water for first 24 h and then 1 wk. The fluoride release was measured after each of the two periods of time. The fluoride treated specimens released more fluoride than the nontreated ones. This effect was not observed with composite resin specimens which were studied for comparison. Fluoride release from fresh glass ionomer specimens was observed to be 3–10 fold compared to specimens that had matured for 3 days. The release of fluoride from specimens that had been in running water for 29 months was measured and the results were compared with those of earlier measurements. It was found that the release reached a constant level for all tested glass ionomers during the second year.     

Fluoride release and uptake by glass ionomers

The aim was to study the fluoride release 1) from 7 and 15-month-old glass ionomer specimens after treating them with fluoride; 2) from fresh compared with matured material; and 3) from specimens stored for 29 months in running water. Glass ionomer test specimens which had been in running water for first 7 then 15 months were treated with a 50 ppm fluoride solution after which the specimens were again exposed to running water for first 24 h and then 1 wk. The fluoride release was measured after each of the two periods of time. The fluoride treated specimens released more fluoride than the nontreated ones. This effect was not observed with composite resin specimens which were studied for comparison. Fluoride release from fresh glass ionomer specimens was observed to be 3-10 fold compared to specimens that had matured for 3 days. The release of fluoride from specimens that had been in running water for 29 months was measured and the results were compared with those of earlier measurements. It was found that the release reached a constant level for all tested glass ionomers during the second year.     

Solubility and fluoride release in ionomers and compomers.

OBJECTIVE: The degree of solubility and the fluoride release of glass-ionomer cements and "compomers" were determined as a function of time. METHOD AND MATERIALS: Three conventional glass-ionomer cements, three hybrid ionomers, and two compomers were included in the study. Disk-shaped specimens were prepared and immersed in a lactic acid solution. Solubility was evaluated from determinations of loss of mass as a function of time. To evaluate fluoride release, similar specimens were immersed in 50 mL of deionized water to which 50 mL of buffer solution was added. A fluoride ion detector was used to read the concentration of fluoride ion in the overall solution at different times after immersion. RESULTS: Material and time factors had a significant influence on results. The compomers showed less corrosion and fluoride release than the ionomers. Some correlation was found between solubility and fluoride leakage values. CONCLUSION: Components of both the ionomers and compomers that were studied can dissolve in water. The materials leak fluoride ions in amounts that differ according to the characteristics of the individual products.     

Fluoride release from CaF2 and enamel demineralization

The anticaries effect of professional fluoride (F) application has been attributed to calcium-fluoride-like deposits (CaF(2)) formed on enamel, but this has not been clearly demonstrated. We hypothesized that CaF(2) formed on plaque-free enamel by F application would reduce enamel demineralization due to the increase of F availability in fluid of subsequently formed plaque. We created distinct levels of CaF(2) on enamel to evaluate a dose-response effect. Enamel blocks were mounted in contact with a S. mutans test plaque and used in situ by 10 volunteers. F released to the fluid phase of this substrate ("plaque fluid") was measured before a cariogenic challenge. "Plaque fluid" F concentration was highly correlated to the enamel CaF(2) concentration (r = 0.96, p < 0.001) and to consequent enamel demineralization (r = -0.75, p < 0.001). The results suggest that F released to plaque fluid from CaF(2) formed on enamel may play a significant role in the anticaries effect of professionally applied F agents.     

Ion release and cytotoxicity of stainless steel wires

Heat treatment is generally applied to orthodontic stainless steel (SS) wires to relieve the stresses that result from their manipulation by orthodontists. The quality and thickness of the oxide films formed on the surface of heat-treated wires can vary, and it is believed that these oxide films can influence the properties of heat-treated wires. The aim of this study was to investigate the influence of heat treatment and cooling methods on the amount of metal ions released and to examine the cytotoxicity of heat-treated wires. In this study, four types of SS wires (Remanium, Permachrome, Colboloy and Orthos) with a cross-sectional area of 0.41 x 0.56 mm were investigated. These wires were heat-treated in a vacuum, air, or argon environment, and were cooled in either a furnace or a water bath. Four control groups and 24 experimental groups were classified according to the type of wires, heat treatment conditions and cooling methods. In each group, the amount of nickel released as well as its cytotoxicity was investigated. The concentration of dissolved nickel ions in artificial saliva was measured for a period of up to 12 weeks. In all groups, the concentration of dissolved nickel ions in artificial saliva was lowest for the vacuum heat treatment-furnace cooling group and a significant difference was shown compared with the other experimental groups. The concentration of dissolved nickel ions in artificial saliva was highest in the groups heat-treated in air (P < 0.05), while the amount of nickel released was highest in the Remanium and Colboloy (P < 0.05). The cytotoxicity was mild in all the experimental groups but the response index of the air groups was slightly higher than in the other groups. According to these results, SS wires retain their high corrosion resistance and low ion release rate when heat-treated in a vacuum and cooled in a furnace.