基于Diels-Alder反应的可注射缓释水凝胶的制备及其理化性质

本研究旨在通过药物-聚合物偶联物模型和Diels-Alder点击反应制备一种可注射缓释水凝胶。将葛根素与透明质酸通过酰胺键连接得到葛根素-透明质酸偶联物(PUE-HA),将PUE-HA和四臂马来酰亚胺聚乙二醇(4-arm-PEG-MAL)通过Diels-Alder点击反应交联制备了可注射缓释水凝胶(PUE-HA-PEG),并考察了三种不同呋喃(Furan)与马来酰亚胺基(MI)比例对所得水凝胶的胶凝时间、形貌、溶胀度、降解度、葛根素体外释放、水凝胶力学性能以及水凝胶生物相容性等理化性质的影响。与1Furan/1MI和1Furan/2MI水凝胶相比，1Furan/4MI的水凝胶胶凝时间可缩短至1 min。随着MI比例的增加，水凝胶具有更低的降解速率(21 d降解率低于60%),更好的力学性能，缓释释药作用更加明显。实验结果表明，Furan/MI的比例对可注射缓释水凝胶的理化性质具有重大影响。     

超声衰减法检测凝胶成胶过程微结构变化

以戊二醛(Glu)胶联丙烯酰胺(AM)形成的软物质凝胶材料的成胶过程为模型,用超声衰减法检测不同浓度交联剂、温度及不同质量丙烯酰胺形成凝胶的成胶过程的微结构变化.同时用流变仪检测凝胶形成过程中粘弹性等参数的变化.实验表明:丙烯酰胺浓度、交联剂的用量和温度不同,丙烯酰胺形成凝胶的超声衰减系数及所需的时间也不相同,丙烯酰胺浓度越大,超声衰减系数越大,凝胶形成越快;温度越高,交联剂的量越多,丙烯酰胺凝胶形成所需的时间越短.     

pH敏感性可注射型醛基瓜尔豆胶-托普霉素自愈抗菌水凝胶及其性质

微生物感染是当今严重危害人类健康、威胁人类安全的公共卫生问题之一,有效抑制微生物感染特别是抑制其耐药性是当今研究热点,抗生素水凝胶作为一种新型生物响应医学材料,能实现缓释靶位给药,达到清除微生物的目的.本研究以氧化瓜尔豆胶作为生物兼容性好的可降解天然多糖为骨架,通过席夫碱反应(可逆亚胺键)接枝托普霉素制备了一种可自愈、原位注射成型的酸敏性抗菌水凝胶,并研究了它们的流变学、自愈能力、可注射性、pH响应性、生物相容性和体外抗菌性能.结果表明,凝胶能负载相当量的托普霉素,凝胶具有优异的自愈性能、良好的切稀和可注射性,呈现酸敏给药模式.扫描电镜显示所得水凝胶成多孔网络结构,适合药物、细胞或生物大分子的运载,适于微创抗感染治疗手术的实施,具有潜在的应用价值.     

壳聚糖-胶原基可注射水凝胶制备及生物相容性检测

制备了可注射的新型温敏性壳聚糖-甘油磷酸钠-胶原（chitosan-glycerophosphate-collagen,C-GP-Co）水凝胶并检测了其与脂肪间充质干细胞（adipose tissue-derived stem cells,ADSCs）的生物相容性．首先将体积分数2．2％的壳聚糖溶液与质量分数50％的B．甘油磷酸钠溶液按一定比例混合后,将2mg／mL胶原溶液加入上述溶液中混合得到壳聚糖-甘油磷酸钠-胶原水凝胶;随后用扫描电镜观察其微观结构,测定了37℃时的成胶时间并测量水凝胶中提取培养基的渗透压;最后将分离、培养和免疫表型鉴定后的ADSCs接种在C-GP—Co水凝胶中培养,倒置显微镜下观察细胞的生长形态,并用Live／Dead Viability-Cytotoxieity试剂盒染色观察细胞凋亡状况,CCK-8试剂盒测定细胞增殖情况．结果表明C—GP—Co水凝胶37℃的成胶时间为12min,水凝胶内部呈海绵状多孔结构,水凝胶中提取培养基的渗透压为310-330mmol／kg．培养7d后,C-GP-Co水凝胶表面的ADSCs贴壁生长,并显示出良好的细胞活性．上述结果表明制备的C-GP-Co水凝胶具有良好的细胞相容性,可作为ADSCs生长增殖的良好支架．     

生物炭水凝胶固定微生物处理含酚废水

筛选和分离出一种高效的苯酚降解菌Bacillussp.26,以西瓜生物炭水凝胶作为载体,用海藻酸钠作为交联剂包埋该菌株.通过实验研究对比灭活的固定化Bacillus sp.26细胞对苯酚的吸附;固定化Bacillus sp.26细胞对苯酚的吸附和降解;游离Bacillus sp.26细胞对苯酚的降解能力.结果表明:Ba...     

硝基苯高效降解菌群对硝基苯好氧降解

硝基苯为环境有毒有害物质,好氧条件下硝基苯的生物降解主要通过部分还原途径.吡啶甲酸作为副产物出现在硝基苯的部分还原途径中.生物毒性大,阻碍了硝基苯的降解.本实验分离出3株在好氧条件下以硝基苯为惟一碳、氮、能源的菌株,分别鉴定为Streptomyces albidoflavus(微白黄链霉菌)、Rhodotorula mucilaginosa(胶红酵母)和Micrococcus luteus(藤黄微球菌),并借助其完整细胞考查了由上述3株菌混合而成的菌群对硝基苯的好氧降解.结果表明:硝基苯经部分还原生成2-氨基酚,2-氨基酚再进一步开环降解.在2-氨基酚开环过程中,有吡啶甲酸生成,毗啶甲酸被矿化成二氧化碳和水.     

壳聚糖/β-甘油磷酸钠水凝胶 与显影剂的体外实验研究

目的通过体外实验探讨显影剂对于壳聚糖/β-甘油磷酸钠水凝胶性能的影响.方法在壳聚糖/β-甘油磷酸钠水凝胶中加入不同的显影剂:泛影葡胺(康瑞),碘帕醇(碘必乐),碘克沙醇(威视派克),研究显影剂对凝胶化的动力学、机械性能、析出时间的影响,以寻找与壳聚糖/β-甘油磷酸钠水凝胶栓塞脑动静脉畸形相匹配的最佳显影剂.结果壳聚糖/β-甘油磷酸钠水凝胶具有良好的生物相容性、温度敏感性、高黏度的优点,加入一定浓度的显影剂没有妨碍温敏性壳聚糖水凝胶的形成,适合栓塞注射.结论 20%威视派克与壳聚糖/β-甘油磷酸钠混合后成胶时间适中,适合脑动静脉畸形栓塞注射.     

天然高分子多糖基载药水凝胶研究进展

生物材料是推动生物医学日新月异发展的基石,医用载药水凝胶作为重要成员,近年来呈现蓬勃发展的态势.通过文献检索,介绍了以透明质酸、壳聚糖、海藻酸盐、结冷胶、果胶、瓜尔胶、Salecan、葡聚糖、纤维素、黄原胶为基底材料的10种天然高分子多糖基水凝胶,并结合课题组在该领域的系列研究进展,综述了天然高分子多糖基水凝胶作为不同...     

光交联羧甲基壳聚糖衍生物水凝胶的制备及性能研究

以叠氮基团的光耦合反应为交联反应制备了叠氮化羧甲基壳聚糖(AZ-CMCS)水凝胶。利用FT-IR红外光谱、1H-NMR核磁共振谱表征了AZ-CMCS的结构,使用紫外可见分光光度计和流变仪跟踪了AZ-CMCS凝胶的光交联过程,并验证了凝胶的可注射性.使用水接触角测试仪表征了凝胶的亲疏水性.以牛血清白蛋白(BSA)为模型药物研究了水凝胶在不同pH值下的药物释放性能,并研究了人胚胎肺成纤维细胞(MRC-5)在水凝胶上的生长情况.结果表明:通过紫外光照射可快速得到AZ-CMCS水凝胶,反应条件温和,易于控制;AZ-CMCS水凝胶具有较好的可注射性,且具有一定的pH响应性,其能够实现包载药物和药物控释的功能;此外AZ-CMCS水凝胶对细胞无毒,可作为细胞支架,具有较好的应用前景.     

清水配置冻胶在盐水中稳定性的变化研究

本文以水溶性酚醛树脂为交联剂,以纳米颗粒为稳定剂,以HPAM以及不同AMPS含量的聚合物为成胶剂,在低盐含量的模拟注入水中制备了稳定的冻胶。研究发现,相同交联剂和聚合物用量下,AM-AMPS共聚物成胶时间比HPAM长,但成胶后强度高。评价了制备的冻胶在不同盐含量模拟水中的脱水情况,结果表明,当模拟水盐含量为10000mg/L、30000mg/L时,冻胶会吸水膨胀、强度降低;但当模拟水盐含量高于50000mg/L时,冻胶则脱水,冻胶强度提高。模拟水盐含量越高,脱水幅度越大。提高冻胶中纳米颗粒的含量或用AMPS含量高的共聚物做成胶剂,可明显降低冻胶在高盐含量中的脱水幅度。研究结果对红河油田裂缝封堵剂的开发有指导意义。     

Multi-membrane hydrogels

Polysaccharide-based hydrogels are useful for numerous applications, from food and cosmetic processing to drug delivery and tissue engineering. The formation of hydrogels from polyelectrolyte solutions is complex, involving a variety of molecular interactions. The physical gelation of polysaccharides can be achieved by balancing solvophobic and solvophilic interactions. Polymer chain reorganization can be obtained by solvent exchange, one of the processing routes forming a simple hydrogel assembly. Nevertheless, many studies on hydrogel formation are empirical with a limited understanding of the mechanisms involved, delaying the processing of more complex structures. Here we use a multi-step interrupted gelation process in controlled physico-chemical conditions to generate complex hydrogels with multi-membrane 'onion-like' architectures. Our approach greatly simplifies the processing of gels with complex shapes and a multi-membrane organization. In contrast with existing assemblies described in the literature, our method allows the formation of free 'inter-membrane' spaces well suited for cell or drug introduction. These architectures, potentially useful in biomedical applications, open interesting perspectives by taking advantage of tailor-made three-dimensional multi-membrane tubular or spherical structures.     

Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles

Protein-based hydrogels are used for many applications, ranging from food and cosmetic thickeners to support matrices for drug delivery and tissue replacement. These materials are usually prepared using proteins extracted from natural sources, which can give rise to inconsistent properties unsuitable for medical applications. Recent developments have utilized recombinant DNA methods to prepare artificial protein hydrogels with specific association mechanisms and responsiveness to various stimuli. Here we synthesize diblock copolypeptide amphiphiles containing charged and hydrophobic segments. Dilute solutions of these copolypeptides would be expected to form micelles; instead, they form hydrogels that retain their mechanical strength up to temperatures of about 90 degrees C and recover rapidly after stress. The use of synthetic materials permits adjustment of copolymer chain length and composition, which we varied to study their effect on hydrogel formation and properties. We find that gelation depends not only on the amphiphilic nature of the polypeptides, but also on chain conformations--alpha-helix, beta-strand or random coil. Indeed, shape-specific supramolecular assembly is integral to the gelation process, and provides a new class of peptide-based hydrogels with potential for applications in biotechnology.     

甲基纤维素温敏水凝胶的凝固及体外释药特性

为研究新型反向温敏凝胶在植入型药物释放系统中的应用,通过粘度跟踪法考察了“甲基纤维素聚乙二醇柠檬酸钠”三组分体系在体温下的凝固特性,分析了凝胶配方对于凝固过程的影响;以5-氟尿嘧啶为模型药物,研究了凝胶配方对体外释放特性的影响。结果表明,甲基纤维素使体系具有反向温敏性,高分子量聚乙二醇具有加速胶凝的作用,柠檬酸钠的盐析作用能降低成胶温度。通过调整凝胶配方,能使体系在体温下在10m in内迅速凝固,并使5-氟尿嘧啶的释放时间达到24 h以上。     

Novel enzymatically crosslinked chitosan hydrogels with free-radical-scavenging property and promoted cellular behaviors under hyperglycemia

The impairment of regenerative processes induced by high blood-glucose level (hyperglycemia) and excessive reactive oxygen species (ROS) contributes to the diabetic complication progression and development. In this study, an injectable, in situ crosslinkable chitosan hydrogel with ROS-scavenging capability was developed by conjugating gallic acid onto the chitosan backbone (CGA). We hypothesized that gallic acid serves as both antioxidant and crosslinking moieties to form hydrogel in situ by means of enzymatic crosslinking with horseradish peroxidase (HRP). The rapid gelation (from 30 s) was observed by vial tilting. The mechanical properties and microstructures of CGA hydrogels can be well controlled by varying the concentrations of H₂O₂. The ROS-scavenging ability of these CGA hydrogels was demonstrated against DPPH radical, hydroxyl radical, and total reducing power. Notably, in an in vitro hyperglycemia environment, CGA hydrogels significantly improved the proliferation and migration of human dermal fibroblast cells, which are closely related to diabetic wound healing. These results suggest that CGA hydrogels have potential as advanced materials for the treatment of diabetes-related diseases via attenuating the excessive ROS production and improving cellular behaviors.     

Aldehyde-Sodium Alginate and Amino-Gelatin Preparation as Soft Tissue Adhesive

Sodium alginate and gelatin are both remarkable natural biomaterials; they all have been extensively applied in tissue engineering and other relative fields,due to their low price and good biocompatibility. In this paper,we oxidized sodium alginate with sodium periodate to convert 1,2-hydroxyl groups into aldehyde groups to get aldehyde-sodium alginate（ A-SA）. Gelatin was modified with ethylenediamine（ ED） in the presence of water-soluble1-ethyl-3（ 3-dimethylaminopropyl） carbodiimide（ EDC） to introduce additional amino groups to get amino-gelatin. Upon mixing the A-SA and amino-gelatin aqueous solutions together,a gel rapidly formed based on the Schiff＇s base reaction between the aldehyde groups in A-SA and the amino groups in amino-gelatin.Fourier transform infrared spectroscopy（ FTIR） analysis confirmed the characteristic peak of Schiff＇s base group in the hydrogel. The gelation time measure has confirmed the gelation time is dependent on the aldehyde group content in A-SA and amino group content in amino-gelatin. The fasted hydrogel formation takes place within 30 s. The entire test suggested that this gel could be a promising candidate as soft tissue adhesive.     

无氨复合凝胶的制备及其胶凝特性

 为了提高凝胶的防灭火性能及热稳定性,用光电分析法研究了新型无氨复合凝胶的胶凝特性。采用光电法测出无氨复合凝胶的成胶时间,分析温度对复合凝胶成胶时间影响,并在同环境下对比了普通凝胶和复合凝胶的热稳定性。结果表明,复合凝胶的成胶时间随环境温度的升高而缩短,且环境温度对成胶时间的影响程度与复合胶凝剂的质量分数有关,影响程度为：6%的胶凝剂＞8%的胶凝剂＞10%的胶凝剂。Na₂SiO₃·nH₂O溶液中添加含有多种Lewis酸的复合胶凝剂后,中和了硅酸胶团的电荷,破坏硅酸胶团的融合膜,促使胶粒发生沉聚而转变为有弹性的凝胶,并且复合胶凝剂的粒度为破碎多面体,进而增加了比表面积,增加了吸水量,提高了热稳定性。     

AM/DMDAAC共聚水凝胶的电场敏感性能

 为研究阳离子性DMDAAC共聚物水凝胶的电场敏感性能,以丙烯酰胺(AM)和二甲基二烯丙基氯化铵(DMDAAC)为单体,N,N'-亚甲基双丙烯酰胺为交联剂,过硫酸铵和亚硫酸氢钠为氧化还原引发剂,采用水溶液聚合法制备了AM/DMDAAC共聚物水凝胶,考查样品水凝胶在外加直流电场刺激下的消溶胀动力学和弯曲行为。研究表明,DMDAAC单体含量、施加电压的时间和施加电压大小以及所在溶液的离子强度对水凝胶的电敏感性能有着显著影响,有望使其在化学阀、仿生驱动器方面得到应用。在低浓度NaCl溶液中向正极弯曲,随着NaCl质量分数的增加,向正极弯曲角度逐渐减小,并进一步向负极弯曲。影响凝胶弯曲角度转变的临界NaCl质量分数为0.3%—0.4%,不同的单体配比,其临界NaCl质量分数也不一样。     

长成冻时间的深部调驱剂研究

长成冻时间的深部调驱剂是以 HPAM为主的复配聚合物 ,由树脂交联剂 1 0 3交联形成的 .由冻胶强度级别的划分定性地测定成冻时间和突破真空度的方法定量测定冻胶强度 .评价了不同聚合物、交联剂及矿化度在不同温度下的成冻时间及强度 ,并作出了成冻时间及强度等值图 .结果表明 :成冻时间在 1～ 3 0 d范围内可调 ,强度 (即 p BV值 )在 - 0 .0 6 0～ - 0 .0 3 0 MPa范围内可调 .由成冻时间和强度等值图可找出具体地层条件下的不同成冻时间及不同强度调驱剂配方     

室温下水凝胶合成的新型方法及测试研究

旨在报道一种新型的水凝胶因子,可在室温下形成凝胶。通过向安替比林-环己烷羰基酯(物质1)的乙醇溶液中加入定量的水可原位、即刻形成凝胶,利用有机合成方法得到了含有吡唑啉酮和环己胺基团的凝胶因子,通过IR,XRD,SEM,TEM等手段对凝胶进行了表征。研究发现,在水含量较低时,凝胶因子分子聚集成为囊泡形状;随着含水量的增大,它的聚集体能实现由0D囊泡向不规整的2D片状结构的转变,并胶凝溶剂。