具有抗菌功能的聚乳酸基纳米纤维膜的构建及生物学评价

材料表界面改性技术是实现材料性能可控制备,赋予其功能的关键。该研究采用喷纺技术制备了以聚乳酸(PLA)为基体的纳米纺丝可吸收高分子生物膜,并通过等离子体处理技术引入氨基,经过戊二醛将单宁酸接枝至纤维表面,有效提高了PLA膜的亲水性能。利用单宁酸的还原功能将纳米银原位沉积到纳米纤维膜表面,有效提高了纤维膜的抗菌性能。体外细胞学评估表明该材料具有良好的细胞相容性,有望作为抗菌功能可吸收生物膜用于抗感染皮肤创面修复。     

聚（L-丙交酯-co-乙交酯）的制备及性能研究

以辛酸亚锡为催化剂、1,4-丁二醇为引发剂,在高温、高真空条件下本体开环聚合制备了乙交酯与L-丙交酯质量比例为6∶4的聚（L-丙交酯-co-乙交酯）（PLGA）。通过IR、^1H NMR对聚合物的结构进行了表征,用DSC、TGA、XRD、流变仪等对聚合物的热性能、结晶性、流变性能进行了研究。研究结果表明PLGA具有较高的热稳定性,且是以非晶态存在的;其熔融流体为剪切变稀流体,储能模量较低,损耗模量较高。     

壳聚糖／魔芋葡甘聚糖共混膜细胞毒性和机械性能研究

目的利用天然高分子材料壳聚糖（CS）和魔芋葡甘聚糖（KGM）制备两者含量不同比例的生物膜,测定其细胞毒性和机械性能。方法流延法制备CS与KGM含量不同比例的混合膜。并将其与人脐带间充质干细胞联合培养,观察其细胞毒性：测定其断裂伸长率、拉伸强度及吸水率。结果CS/KGM含量比例分别为3：0、2：1、1：1和1：2制备的8种共混膜,具有良好的细胞毒性：膜平均厚度0．110mm,拉伸强度为35．84～48．17MPa,断裂伸长率为4．84％-6．25％,吸水率均随着CS含量增加而增加。结论CS／KGM含量比为3：0、2：1、1：1和1：2制备的共混膜,都具有良好的细胞毒性,初步具备了引导组织再生膜的基本性能。     

姜黄素/聚乳酸－乙醇酸共聚物复合薄膜的制备及抗凝血研究

血管支架内再狭窄是血管支架临床应用中最突出的问题,药物洗脱支架的问世成为冠心病介入治疗的一个重要里程碑.但是目前的药物洗脱支架还存在抗凝血不足的问题,药物洗脱支架植入晚期血栓形成的病例在临床上有所报道.姜黄素具有抗增生以及抗凝血等多种药理活性,有望成为药物洗脱支架的新颖药物.我们以可降解高分子材料聚乳酸-乙醇酸共聚物(PLGA)为载体分别制备了三种浓度(3wt%、5wt%、8wt%)的姜黄素复合薄膜.采用傅立叶变换红外光谱研究了复合薄膜的组成成分,结果显示:姜黄素与PLGA的特征峰在复合薄膜的红外图谱中均有出现;体外血小板黏附实验结果显示姜黄素复合薄膜表面的血小板黏附数量减少,较少团聚、变形和激活;复合薄膜的部分凝血活酶时间(APTT)长于纯PLGA薄膜的APTT,这都表明姜黄素/聚乳酸-乙醇酸共聚物复合薄膜的抗凝血性能得到改善,且复合薄膜的抗凝血性能在实验药物浓度范围内随着药物含量的增加,材料的抗凝血性能进一步提高.     

不同液晶类型的聚氨酯/液晶复合膜的血液相容性

本研究合成了三种亲水性胆甾醇液晶化合物 ,用元素分析法、红外光谱、差热分析以及偏显镜观察对其结构和性能进行了表征。利用聚氨酯与上述液晶化合物制备复合膜 ,研究了不同液晶类型对聚合物 /液晶复合膜的影响。研究表明 ,胆甾醇液晶化合物有利于改善聚合物材料的血液相容性     

离心作用测定细胞与材料间的粘附力及其初步应用

目的：介绍一种简单易行的检测细胞与材料间黏附力的方法。方法：本方法的建立基于离心力在转速一定时与半径成正比的原理。医用石膏制备培养皿固定装置，于培养皿底制备材料薄膜（包括有PLGA，PLGA COLI，PLGA COL I FN），待大鼠骨骼肌卫星细胞悬液与其作用一定时间后，一定转速开动离心机。测定未脱落细胞斑的半径R,取均值。结果：上述三种材料表面未脱落大鼠骨骼肌卫星细胞圆斑半径（R）分别为7.96、15.11、26.10mm，三组间有显著性差异。结论：（1）R的变化可反映细胞与材料间粘附力的改变。（2）利用离心作用检测细胞与材料间的粘附力是可行的，尤其适用于同一种细胞与不同材料间粘附力的比较。（3）COL I和FN的使用可以增加大鼠骨骼肌卫星细胞与PLGA间的粘附。     

姜黄素/聚乳酸—乙醇酸共聚物复合薄膜的制备及抗凝血研究

血管支架内再狭窄是血管支架临床应用中最突出的问题,药物洗脱支架的问世成为冠心病介入治疗的一个重要里程碑。但是目前的药物洗脱支架还存在抗凝血不足的问题,药物洗脱支架植入晚期血栓形成的病例在临床上有所报道。姜黄素具有抗增生以及抗凝血等多种药理活性,有望成为药物洗脱支架的新颖药物。我们以可降解高分子材料聚乳酸-乙醇酸共聚物(PLGA)为载体分别制备了三种浓度(3wt%、5wt%、8wt%)的姜黄素复合薄膜。采用傅立叶变换红外光谱研究了复合薄膜的组成成分,结果显示:姜黄素与PLGA的特征峰在复合薄膜的红外图谱中均有出现;体外血小板黏附实验结果显示姜黄素复合薄膜表面的血小板黏附数量减少,较少团聚、变形和激活;复合薄膜的部分凝血活酶时间(APTT)长于纯PLGA薄膜的APTT,这都表明姜黄素/聚乳酸-乙醇酸共聚物复合薄膜的抗凝血性能得到改善,且复合薄膜的抗凝血性能在实验药物浓度范围内随着药物含量的增加,材料的抗凝血性能进一步提高。     

pH敏感性羟乙基甲壳素/聚丙烯酸水凝胶的制备及其释药性能研究

用氯乙醇对甲壳素进行醚化改性，得到水溶性羟乙基甲壳素（Hydroxyethyl chitin，HECH），用化学交联法制备了由聚丙烯酸（PAA）和HECH复合的互穿网络（IPN）水凝胶。溶胀实验表明：该水凝胶在人工肠液（pH7．4，I=0．1）中的溶胀度远大于在人工胃液（pH）．4，I=0．1）中的溶胀度，凝胶的溶胀度随着温度的升高而增大；以该凝胶制备了双氯芬酸钾缓释体系，释放实验表明该凝胶具有较好的缓释性能。     

壳聚糖的接枝改性及其在生物医学领域中的应用前景

按接枝物的不同类型,分别综述了壳聚糖与小分子单体、大分子单体、高分子的接枝改性方法的进展。通过接枝共聚改性,可以赋予壳聚糖某些新性能,例如亲水性、功能性、智能性等,这些独特的性能使壳聚糖接枝改性产物在生物医学上有很好的应用前景。     

溶胶-凝胶法制备纳米羟基磷灰石超薄薄膜及其表征

分别使用有机溶胶-凝胶以及无机溶胶作为羟基磷灰石（HA）前驱体，利用浸渍涂层（Dip-coating）技术在钛表面制备纳米超薄薄膜。利用扫描电镜（SEM）和X射线衍射（XRD）表征薄膜形态、微晶尺寸分布（D）和微观应变（ε）。结果表明：在大于400℃热处理后，薄膜开始呈现磷灰石结构；在400℃～600℃范围内，热处理温度对两种磷灰石薄膜D和ε的影响显著；SEM结果证明HA前驱体种类严重影响两种纳米HA薄膜的颗粒团聚尺寸；有机溶胶-凝胶和无机凝胶在钛表面制备的HA薄膜颗粒团聚尺寸分别为25nm和100nm，薄膜厚度分别为2．5μm和5．0μm。浸渍涂层技术制备的HA薄膜表面／界面形态完整，薄膜表面无明显微裂纹。     

载紫杉醇PLGA/F68纳米粒逆转多药耐药用于乳腺癌的治疗

目的载紫杉醇聚乳酸聚羟基乙酸共聚物（PLGA）/F68纳米粒逆转耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞多药耐药的可行性研究。方法使用超声乳化溶剂挥发法分别制备载紫杉醇PLGA和载紫杉醇PLGA/F68纳米粒（10%）,并对载紫杉醇纳米粒进行表征。载紫杉醇纳米粒的体外释放研究使用高效液相色谱进行分析。最后研究载紫杉醇纳米粒在耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞的细胞摄取和细胞毒性（PLGA/F68组、PLGA组和泰素组）。结果纳米粒呈球形,表面粗糙多孔,平均粒径250 nm左右,粒径分布比较窄,体外药物释放呈双相释放模型。载紫杉醇PLGA/F68纳米粒能够被耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞摄取。载紫杉醇PLGA/F68纳米粒比载紫杉醇PLGA纳米粒（P〈0.05）和泰素（TaxolR）（P〈0.05）有更高的细胞毒性。结论载紫杉醇PLGA/F68纳米粒能够逆转耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞的多药耐药,药用辅料Pluronic F68在乳腺癌治疗中具有潜在的应用前景。     

星型M-PLGA纳米药物制剂用于宫颈癌治疗的研究

目的 本研究合成了一种星型的甘露醇引发的聚（乳酸-羟基乙酸）共聚物（M-PLGA）,旨在提供一种新型的纳米制剂用于宫颈癌的治疗.方法 这种新型的共聚物通过开环聚合合成,利用核磁共振仪进行表征.采用改进的纳米沉淀法制备载多烯紫杉醇M-PLGA纳米粒并在扫描电镜下观察纳米粒的形态.结果 M-PLGA纳米粒粒径分布较窄,在人宫颈癌Hela细胞中的摄取水平要高于PLGA纳米粒.载多烯紫杉醇的M-PLGA纳米粒对Hela细胞的毒性显著高于商用的泰素帝和载多烯紫杉醇的PLGA纳米粒,证明星型M-PLGA聚合物作为纳米药物载体优于线型PLGA聚合物;同时,星型M-PLGA的载药量也明显高于线型聚合物.结论 星型M-PLGA共聚物可作为一种极具潜力的用于宫颈癌治疗的纳米载体材料.     

Asymmetrically porous PLGA/Pluronic F127 membrane for effective guided bone regeneration

Porous guided bone regeneration (GBR) membranes with selective permeability, hydrophilicity and adhesiveness to bone were prepared with PLGA and Pluronic F127 using an immersion precipitation method. The porous PLGA/Pluronic F127 membranes were fabricated by immersing the PLGA/Pluronic F127 mixture solution (in tetraglycol) in a mold into water. The PLGA/Pluronic F127 mixture was precipitated in water by the diffusion of water into PLGA/Pluronic F127 mixture solution. It was observed that the membrane has an asymmetric column-shape porous structure. The top surface of the membrane (water contact side) had nano-size pores (approx. 50 nm) which can effectively prevent from fibrous connective tissue invasion but permeate nutrients, while the bottom surface (mold contact size) had micro-size pores (approx. 40 microm) which can improve adhesiveness with bone. From the investigations of mechanical property, water absorbability, model nutrient permeability and preliminary in vivo bone regeneration, the hydrophilized porous PLGA/F127 (5 wt%) membrane seems to be a good candidate as a GBR membrane for the effective permeation of nutrients and osteoconductivity, as well as good mechanical strength to maintain a secluded space for bone regeneration.     

Asymmetrically porous PLGA/Pluronic F127 membrane for effective guided bone regeneration

Porous guided bone regeneration (GBR) membranes with selective permeability, hydrophilicity and adhesiveness to bone were prepared with PLGA and Pluronic F127 using an immersion precipitation method. The porous PLGA/Pluronic F127 membranes were fabricated by immersing the PLGA/Pluronic F127 mixture solution (in tetraglycol) in a mold into water. The PLGA/Pluronic F127 mixture was precipitated in water by the diffusion of water into PLGA/Pluronic F127 mixture solution. It was observed that the membrane has an asymmetric column-shape porous structure. The top surface of the membrane (water contact side) had nano-size pores (approx. 50 nm) which can effectively prevent from fibrous connective tissue invasion but permeate nutrients, while the bottom surface (mold contact size) had micro-size pores (approx. 40 μm) which can improve adhesiveness with bone. From the investigations of mechanical property, water absorbability, model nutrient permeability and preliminary in vivo bone regeneration, the hydrophilized porous PLGA/F127 (5 wt%) membrane seems to be a good candidate as a GBR membrane for the effective permeation of nutrients and osteoconductivity, as well as good mechanical strength to maintain a secluded space for bone regeneration.     

聚吡咯/PLGA可导电复合纳米纤维支架对肝细胞生物相容性的研究

目的 评估聚吡咯/PLGA可导电复合纳米纤维支架对肝细胞的生物相容性.方法 采用静电纺丝及氧化结合法制备聚吡咯/PLGA可导电复合纳米纤维支架,并对其进行电镜表征及电化学检测.采用2步原位胶原酶法分离培养大鼠原代肝细胞.实验组将大鼠肝细胞培养于聚吡咯/PLGA可导电复合纳米纤维支架表面,而对照组设为PLGA培养组及空白对照组;采用MTT法检测各组细胞活性,BCA试剂盒评估各组细胞数量,ELISA法检测白蛋白分泌及尿素合成,同时还测定了各组肿瘤坏死因子-α（TNF-α）及乳酸脱氢酶（LDH）的浓度.结果 MTT实验及BCA检测提示聚吡咯/PLGA组与PLGA组间细胞数量及活性差异无统计学意义,但相比空白对照组其差异均具有统计学意义（P＜0.05）.白蛋白分泌及尿素合成方面也有类似表现,聚吡咯/PLGA组与PLGA组间差异无统计学意义,但较空白对照组要好.各组TNF-α及LDH的浓度差异无统计学意义（P＞0.05）.结论 聚吡咯/PLGA可导电复合纳米纤维支架具有良好的生物相容性,可以作为肝脏组织工程中肝细胞黏附介质的理想材料.     

盐酸多柔比星缓释植入剂体外释药与体外降解的研究

以聚（乳酸-羟基乙酸）共聚物（PLGA）为载体制备盐酸多柔比星缓释植入剂,测定植入剂的释放度和PLGA失重率,结果表明PLGA体外降解曲线呈＂S＂形,起初的迟缓期后降解速率加快,5周时失重率达80%。植入剂表现出趋于零级的药物释放模式（r=0.9880）,在0~25 d日均释放度达3.26%,35 d时累积释放度达90%以上。植入剂可持续释药1个月,释药速率主要取决于PLGA降解速率,通过调节PLGA降解速率可以很好地控制药物的释放度。     

Chitosan-coated alginate membranes for cultivation of limbal epithelial cells to use in the restoration of damaged corneal surfaces

Some chemicals or thermal burns may result in abnormal reepithelialization by conjunctival epithelial cells and it causes different types of damage on the cornea surface. When reepithelialization does not occur, chronic inflammation and neovascularization develop, often leading to stroma scarring and/or ulceration. The aim of this study is to restore the human corneal surface with autologous corneal epithelial sheets generated by serial cultivation of the limbal epithelial cells over the different compositions of composite membranes. The composite membranes were prepared by coating the alginate membrane with chitosan. In this method, alginate membrane was prepared by precipitation of the sodium alginate solution in calcium chloride solution. Alginate membranes were washed, dried and immersed into the chitosan solutions to prepare composite membranes. The composite membranes were characterized based on their morphology, hydrophilicity, swellability, and chemical structure. In the last part of the study, composite membranes were used as base matrices for limbal epithelial cell cultivation. The cell cultivation on polymeric membranes was investigated as the in vitro studies. In these studies cell attachment, spreading and growth on polymeric membranes were evaluated.     

Fabrication and characterization of hydrophilic poly(lactic-co-glycolic acid)/poly(vinyl alcohol) blend cell scaffolds by melt-molding particulate-leaching method

Porous PLGA/PVA scaffolds were fabricated by blending poly(lactic-co-glycolic acid) (PLGA) with polyvinyl alcohol (PVA) to improve the hydrophilicity and cell compatibility of the scaffolds for tissue engineering applications. PLGA/PVA blend scaffolds with different PVA compositions up to 20wt% were fabricated by a melt-molding particulate-leaching method (non-solvent method). The prepared scaffolds were investigated by scanning electron microscopy (SEM), mercury intrusion porosimetry, the measurements of water contact angles and bi-axial tensile strengths, etc. for their surface and bulk characterizations. The scaffolds exhibited highly porous and open-cellular pore structures with almost same surface and interior porosities (pore size, 200-300 microm; porosity, about 90%). The PLGA/PVA blend scaffolds with PVA compositions more than 5% were easily wetted in cell culture medium without any prewetting treatments, which is highly desirable for tissue engineering applications. In vitro cell compatibility of the control hydrophobic PLGA and hydrophilized PLGA/PVA (5wt%) blend scaffolds was compared by the culture of human chondrocytes in the scaffolds and the following analyses by MTT assay and SEM observation. It was observed that the PLGA/PVA blend scaffold had better cell adhesion and growth than the control PLGA scaffold. For in vivo evaluation of tissue compatibility, the scaffolds were implanted into the skull defects of rabbits. The results were evaluated by histology examinations. The PLGA/PVA (5wt%) blend scaffold showed better bone ingrowth into the scaffold and new bone formation inside the scaffold than the PLGA scaffold. It seems that 5% addition of PVA to PLGA to fabricate PLGA/PVA blend scaffolds is enough for improving the hydrophilicity and cell compatibility of the scaffolds.     

Preparation and characterization of ibuprofen-loaded poly(lactide-co-glycolide)/poly(ethylene glycol)-g-chitosan electrospun membranes

Ibuprofen-loaded composite membranes composed of poly(lactide-co-glycolide) (PLGA) and poly(ethylene glycol)-g-chitosan (PEG-g-CHN) were prepared by electrospinning. The electrospun membranes were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), mechanical evaluation and contact angle measurements. Shrinkage behavior of the membrane in buffer at 37 degrees C was also evaluated. It was found that PLGA glass transition temperature (Tg) decreased with increasing PEG-g-CHN content in the composite membranes, which results in a decrease in tensile stress at break but an increase in tensile strain of the membranes. The degree of shrinkage of these composite membranes decreased from 76 to only 3% when the PEG-g-CHN content in the membranes increased from 10 to 30%. The presence of PEG-g-CHN significantly moderated the burst release rate of ibuprofen from the electrospun PLGA membranes. Moreover, ibuprofen could be conjugated to the side chains of PEG-g-CHN to prolong its release for more than two weeks. The sustained release capacity of the PLGA/PEG-g-CHN composite membranes, together with their compliant and stable mechanical properties, renders them ideal matrices for atrial fibrillation.