【作者】 张媛；

【导师】 丁辛；

【作者基本信息】 东华大学 ， 纺织工程， 2015， 硕士

【摘要】 静电纺是目前连续制备纳米纤维最有效的方法，纳米纤维网因具有高的比表面积和孔隙率，被广泛地应用在组织工程领域。组织工程的核心是制备生物材料支架来模拟天然细胞外基质的结构和功能，然而在组织工程中，纤维支架上担载的往往是一些具有生物活性的药物，为避免其失活，制备载药纤维时，一般会预先对药物处理，使其形成外有保护层的微球药物，但是处理后形成的微球药物直径较大，纳米纤维支架不能有效地担载此类颗粒药物，更达不到控制其释放的功能。针对上述问题，少数学者目前已经初步实现了利用静电纺串珠结构纤维来担载组织工程中的颗粒型药物，缓解了药物突释现象。串珠结构纤维，即在连续的纳米尺度的纤维上生成了直径相对较大的珠粒,当纺丝液自身在纺丝过程中能形成串珠结构纤维时，可将微球药物担载于珠粒中。但问题是，串珠纤维的结构受到多重因素的影响，其制备过程极不稳定，而实现担载颗粒药物的前提就是必须要存在稳定的串珠结构，目前还没有系统的研究工作针对如何控制串珠纤维形态、尺寸以及串珠的数量而展开，针对上述问题，本文以串珠结构纤维为研究对象，主要工作包含以下几部分：(1)稳定地制备串珠纤维。课题通过分析串珠纤维产生的机理和影响因素，以浓度为切入点，选用可纺性较好的聚氧化乙烯(PEO)为纺丝材料，通过单一控制浓度稳定地纺出串珠纤维，采用光学显微镜和SEM观察静电纺纤维形态。(2)调节和表征串珠纤维尺寸和珠粒数量。课题在稳定制备串珠纤维的前提下，进一步研究浓度、电压、纺丝距离和流速这4个重要因素对珠粒直径、珠粒之间的纤维直径和珠粒数量的影响。在串珠纤维形成的浓度范围内，选择4种不同浓度来研究浓度的影响；选择浓度为6.0wt%的PEO水溶液来研究电压、纺丝距离和流速的影响。采用ImageJ和SPSS统计和分析数据。(3)制备载药串珠纤维。课题以不溶于水的紫杉醇作为颗粒模型药物，选择合适的纺丝参数制备串珠纤维和光滑纤维。通过串珠纤维载药前后对比试验，观察加药前后串珠纤维尺寸和珠粒数量有无变化，来研究颗粒药物对静电纺串珠纤维的影响；通过串珠纤维和光滑纤维载药对比实验，观察两种纤维担载药物的表面形态，来判定是否光滑纤维不具备担载颗粒药物的能力。结果显示：将PEO的浓度控制在2.5wt%~7.0wt%内，可以稳定地制备串珠纤维。适当提高浓度和流速、降低电压可以提高纤维和珠粒直径；适当降低浓度和电压、增加流速和纺丝距离可以增加珠粒数量，且所有纺丝条件下得到的珠粒之间纤维平均直径可以有效地控制在50~500nm之内，珠粒的直径能达到1~2μm，有的甚至达到3~4μm。加入颗粒药物后纺丝，串珠纤维表面没有发现裸露的颗粒，然而在光滑纤维表面上分布着裸露的不规则颗粒或者纤维表面有一些锯齿形颗粒突出，这说明只有纤维本身具有串珠结构才能有效担载颗粒药物，此外药物颗粒的加入不会影响串珠纤维上珠粒本身的尺寸和数量。更多还原

【Abstract】 Electrospinning has been regarded as a prevailing method to fabricate nanofibers.The benefits of high surface to volume ratio and high porosity contribute to apromising application in the field of tissue engineering. The core of tissue engineeringis to prepare biomaterial scaffolds to mimic natural extracelluar matrix(ECM). Greatefforts have been made to encapsulate model drugs into electrospun nanofiberscaffolds. However, many drugs such as protein are easily inactivated when exposedto chemical environment.So it should be covered before electrospinning. However, fordrugs in such particulate form, it remains a challenge to well encapsulate them intothe ultrafine fibers completely, not to mention a sustainable drug release.To ensure a proper encapsulation of particle drugs by electrospun nanofibers,proposals have been put forward to use beaded nanofibers as drug carriers.The beadsin fibers own diameters up to several microns and therefore have sufficient capacityfor particle drugs. However, the process of preparing beaded nanofibers is unsteadyand the beads-on-string stucture is the premise of drug encapsulation. However, fewattentions have been paid to this stucture to discover the conditions for formingbeaded nanofibers and controlling the size of beaded nanofibers. Based on this goal,contents of the study and the corresponding conclusions are as follow:(1) Fabrication of electrospun beaded nanofibers. The concentration was selectedas the key factor to control the formation of beaded nanofibers. PEO was selected toprepare the spinning solutions in consideration of good spinnability. The morphologyof nanofibers was observed under an optical microscope and a scanning electronmicroscope.(2) Adjustment and charaterization of the size for beaded nanofibers. On thepremise of the stable preparation for beaded nanofibers, further studies about theeffects of concentration,voltage, spinning distance and velocity on the variationtendency of fiber diameter, bead diameter and bead number were conducted.4 different PEO concentrations were selected to study the influence of concentration onthe size. The6.0wt%PEO aqueous solution was used to study the influence ofspinning parameters on the size. SPSS and MATLAB softwares were used to analyzethe effects of main factors above on the size of beaded nanofibers.(3) The encapsulation of drug particles by beaded nanofibers. The paclitaxel wasselected as the model drug particles. Suitable spinning parameters were selected tofabricate beaded fibers and smooth fibers respectively.The first contrast experimentwas conducted to observe the variation of beaded nanofibers with and without drugs.Through analyzing whether drugs can cause a change in the size to acess the impactof drug particles on beaded nanofibers. The second contrast expriment was to observewhether particles on the surface of fibers to assess the encapsulation efficiency ofbeaded nanofibers and smooth fibers.The results showed that beaded nanofibers were stably prepared when PEOconcentration was kept in the range of2.5wt%to7.0wt%. when increasing theconcentration and the velocity, lowering the voltage appropriately, fiber diameter andbead diameter both increased. Meantime, when reducing the concentration andvoltage, increasing the flow velocity and the spinning distance appropriately, thenumber of beads increased. At all spinning conditions, the average fiber diameterbetween beads was controlled within50~500nm effectively, and the bead diameterwas up to1~2μm, a small part of beads diameter even could be up to3~4μm. Addingdrug particles during electrospinning, the surface of beaded nanofiber was found nobare particles, while fibers between the beads became thinner. However, a lot of largeparticles distributed on the surface of smooth fibers. As a result, only the fiber itselfhas a beads-on-string structure can effectively embed drug particles. In addition, thebeads size and number are not affected by particle drugs.更多还原