Estudo da reação de modificação química da poliacrilonitrila com grupos 2-oxazolina

Neste trabalho a reação de modificação química da poliacrilonitrila pela incorporação de grupos 2-oxazolina foi estudada através da interação dos grupos nitrila do polímero com 2-amino-etanol catalisada por acetato de cádmio. Os copolímeros foram obtidos em diferentes condições reacionais para alcançar a reação de incorporação do heterocíclico preferencialmente à reação de ciclização dos grupos nitrila que ocorre na presença de catalisador. O grau de modificação química obtido foi relacionado às alterações nas propriedades dos polímeros modificados, que foram caracterizados por espectroscopias na região do infravermelho com transformada de Fourier, do ultravioleta-visível e de ressonância magnética nuclear de hidrogênio, e por calorimetria diferencial de varredura e termogravimetria. As condições ótimas de reação foram alcançadas a 70C após 35h. E o polímero obtido a partir destas condições foi avaliado como inibidor de corrosão para aço-carbono em solução de ácido clorídrico. Sob estas condições experimentais, uma eficiência de inibição de 63 % foi obtida

Failure mechanisms in fibrous scaffolds.

Polymeric fibrous scaffolds have been considered as replacements for load-bearing soft tissues, because of their ability to mimic the microstructure of natural tissues. Poor toughness of fibrous materials results in failure, which is an issue of importance to both engineering and medical practice. The toughness of fibrous materials depends on the ability of the microstructure to develop toughening mechanisms. However, such toughening mechanisms are still not well understood, because the detailed evolution at the microscopic level is difficult to visualize. A novel and simple method was developed, namely, a sample-taping technique, to examine the detailed failure mechanisms of fibrous microstructures. This technique was compared with in situ fracture testing by scanning electron microscopy. Examination of three types of fibrous networks showed that two different failure modes occurred in fibrous scaffolds. For brittle cracking in gelatin electrospun scaffolds, the random network morphology around the crack tip remained during crack propagation. For ductile failure in polycaprolactone electrospun scaffolds and nonwoven fabrics, the random network deformed via fiber rearrangement, and a large number of fiber bundles formed across the region in front of the notch tip. These fiber bundles not only accommodated mechanical strain, but also resisted crack propagation and thus toughened the fibrous scaffolds. Such understanding provides insight for the production of fibrous materials with enhanced toughness.

Failure mechanisms in fibrous scaffolds

Polymeric fibrous scaffolds have been considered as replacements for load-bearing soft tissues, because of their ability to mimic the microstructure of natural tissues. Poor toughness of fibrous materials results in failure, which is an issue of importance to both engineering and medical practice. The toughness of fibrous materials depends on the ability of the microstructure to develop toughening mechanisms. However, such toughening mechanisms are still not well understood, because the detailed evolution at the microscopic level is difficult to visualize. A novel and simple method was developed, namely, a sample-taping technique, to examine the detailed failure mechanisms of fibrous microstructures. This technique was compared with in situ fracture testing by scanning electron microscopy. Examination of three types of fibrous networks showed that two different failure modes occurred in fibrous scaffolds. For brittle cracking in gelatin electrospun scaffolds, the random network morphology around the crack tip remained during crack propagation. For ductile failure in polycaprolactone electrospun scaffolds and nonwoven fabrics, the random network deformed via fiber rearrangement, and a large number of fiber bundles formed across the region in front of the notch tip. These fiber bundles not only accommodated mechanical strain, but also resisted crack propagation and thus toughened the fibrous scaffolds. Such understanding provides insight for the production of fibrous materials with enhanced toughness. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Gelatin nanofiber-reinforced alginate gel scaffolds for corneal tissue engineering.

A severe shortage of donor cornea is now an international crisis in public health. Substitutes for donor tissue need to be developed to meet the increasing demand for corneal transplantation. Current attempts in designing scaffolds for corneal tissue regeneration involve utilization of expensive materials. Yet, these corneal scaffolds still lack the highly-organized fibrous structure that functions as a load-bearing component in the native tissue. This work shows that transparent nanofiber-reinforced hydrogels could be developed from cheap, non-immunogenic and readily available natural polymers to mimic the cornea's microstructure. Electrospinning was employed to produce gelatin nanofibers, which were then infiltrated with alginate hydrogels. Introducing electrospun nanofibers into hydrogels improved their mechanical properties by nearly one order of magnitude, yielding mechanically robust composites. Such nanofiber-reinforced hydrogels could serve as alternatives to donor tissue for corneal transplantation.

Rapid patterning of 1-D collagenous topography as an ECM protein fibril platform for image cytometry.

Cellular behavior is strongly influenced by the architecture and pattern of its interfacing extracellular matrix (ECM). For an artificial culture system which could eventually benefit the translation of scientific findings into therapeutic development, the system should capture the key characteristics of a physiological microenvironment. At the same time, it should also enable standardized, high throughput data acquisition. Since an ECM is composed of different fibrous proteins, studying cellular interaction with individual fibrils will be of physiological relevance. In this study, we employ near-field electrospinning to create ordered patterns of collagenous fibrils of gelatin, based on an acetic acid and ethyl acetate aqueous co-solvent system. Tunable conformations of micro-fibrils were directly deposited onto soft polymeric substrates in a single step. We observe that global topographical features of straight lines, beads-on-strings, and curls are dictated by solution conductivity; whereas the finer details such as the fiber cross-sectional profile are tuned by solution viscosity. Using these fibril constructs as cellular assays, we study EA.hy926 endothelial cells' response to ROCK inhibition, because of ROCK's key role in the regulation of cell shape. The fibril array was shown to modulate the cellular morphology towards a pre-capillary cord-like phenotype, which was otherwise not observed on a flat 2-D substrate. Further facilitated by quantitative analysis of morphological parameters, the fibril platform also provides better dissection in the cells' response to a H1152 ROCK inhibitor. In conclusion, the near-field electrospun fibril constructs provide a more physiologically-relevant platform compared to a featureless 2-D surface, and simultaneously permit statistical single-cell image cytometry using conventional microscopy systems. The patterning approach described here is also expected to form the basics for depositing other protein fibrils, seen among potential applications as culture platforms for drug screening.

可生物降解电纺丝超细纤维

电纺丝技术是一种用来制备超细纤维的方法，成本低廉、简单易行。近十年来，电纺丝技术在理论研究和实验参数研究等方面都取得了不小的进展。由电纺丝技术制备的超细纤维直径至少比传统的纺丝工艺低1-3个数量级，因此，在增强复合材料、过滤系统、防护衣、光学和电学器件及生物医药等方面都显示出巨大的应用潜力。尤其是在生物医药领域，电纺丝超细纤维可广泛用作组织工程支架、药物传输与控制释放的载体及创伤敷料等，这也是国际上的一个研究热点。但由于电纺丝过程的复杂性和实验参数的多样性，制备直径分布范围窄的纤维一直是电纺丝的难点之一，另外，以电纺丝超细纤维作为药物传输与释放的载体也是近两年才刚刚发展起来的，还不十分成熟，经常会存在药物的突释现象。针对以上问题，本论文以可生物降解高分子材料PLA、PLGA（80／20）和PCL进行电纺丝，系统地研究了溶剂体系、表面活性剂、鲜溶液流速、喷丝口直径及环境温度与空气流动速度等因素对电纺丝过程及纤维形貌和直径分布的影响，同时对电纺丝纤维的性质进行了分析。在此基础上，我们研究了PLLA和PCL电纺丝超细纤綷的酶降解行为，并实现了PLLA纤维对抗癌药紫杉醇和1. 以氯仿、氯仿/丙酮、1、2-二氯乙烷及氯仿/1,2-氯乙烷为溶剂体系，制备了PLA、PCL和PLGA（80／20）的电纺丝超细纤维。当氯仿与丙酮的体积比为1：1时为最佳溶剂体系，电纺丝过程和纤维形貌都得到较大的改善。阳离子表面活性剂节基三乙基氯化按（TBBAC）和阴离子表面活性剂十二烷基硫酸钠（SDS）的加入也可以显著改善电纺丝过程和纤维的直径分布，而非离子表面活性剂脂肪醇聚氧乙烯醚（AEO10）的改善程度较小。压力较大或喷丝口直径较粗时，则会由于溶液流量的增大而造成纤维的粘连。空气流速较大时，则纤维会由于空气的对流速度加快而发生缠绕和卷曲。2．PLLA、PCL和PLGA（80／20）超细纤维毡的孔隙率都较大，分别达到89％、68％和80％，因此，PLLA和PCL纤维的力学性能都远远低于膜。3．电纺丝过程会使纤维中的高分子链产生一定的排列和高度的取向，但由于纤维的固化速度很快，高分子链来不及进行规整排列而形成结晶，因此，DSC和WXAD的结果都显示，PCL纤维毡的结晶度要比相应的膜低。对于PLLA纤维毡来说，由于Tg在室温以上，在进行DSC测试的升温过程中，会由于分子链的运动而使结晶度升高。4．蛋白酶K在Tris-HCL缓冲液中略显正电性，因而阴离子表面活性剂对蛋白酶K会有一定的吸附作用，而阳离子表面活性剂对蛋白酶K在纤维表面的吸附则有一定的阻碍作用，因此，含有5wt％SDS的PLLA纤维的酶降解速率比含有swt％TEBAC的PLLA纤维稍快。虽然纤维中PLLA的分子链可能高度取向，但在整个降解过程中，PLLA纤维样品都处在非晶状态，没有明显的结晶行为。5．与PLLA纤维的降解情况恰好相反，由于脂肪酶PS在磷酸盐缓冲液（PBS）缓冲液中显示较强的负电性，因而阳离子表面活性剂TEBAC会对脂肪酶PS有吸附作用，从而含有5wt％TEBAC的PCL纤维降解速度较快，而阴离子表面活性剂SDS会对脂肪酶PS在纤维表面的吸附有阻碍作用，因此，降解反应在含有5wt％SDS的PCL纤维中几乎不能发生。DSC和WAXD的结果均显示，在降解过程中，含有5wt％TEBAC的PCL纤维的结晶度明显升高。这有两个可能原因：一是脂肪酶PS对PCL纤维的降解是优先发生在无定形区：二是因为降解实验是在37℃的条件下进行的，该温度在PCL的Tg之上和TC温度附近，因而，具有高度排列和取向的PCL纤维就会由于分子链的运动而产生结晶，造成结晶度的提局。6，在电纺丝溶液中加入利福平、紫杉醇和阿霉素等药物，同样会改善电纺丝过程，使纤维直径降低，分布变窄。7．SEM照片和药物控制释放实验均显示，药物模型利福平或抗癌药紫杉醇完全被包埋在PLLA纤维内部，同时，利福平一PLLA纤维和紫杉醇－PLLA纤维在含蛋白酶K的Tris-HCl缓冲液中的释放遵循零级动力学，完全没有突释现象。PLLA纤维的降解速度是药物释放的主导因素。这是在国际范围内首次取得这样的结果，从而使电纺丝超细纤维药物剂型的发展取得了本质上的进步。8．药物在溶剂体系中的溶解性及与高分子材料的相容性是影响药物能否被纤维成功包埋的直接因素，一般脂溶性药物易于被脂溶性的高分子纤维包埋。因此，水溶性的盐酸阿霉素难于被包埋在脂溶性的PLLA纤维内部，在纤维外面和表面存在大量盐酸阿霉素的颗粒。相应地，其药物释放行为存在明显的突释现象，这主要是由纤维外面和表面的盐酸阿霉素的溶解、扩散造成的。而经去盐酸化的阿霉素的脂溶性较好，因此，在PLLA纤维中的包埋及释放行为均得到明显的改善，可实现阿霉素的恒速释放，无突释行为。9．SEM照片显示，药物模型利福平被完全包埋在PLGA（80／20）纤维内部，利福平-PLGA（80／20）纤维在PBS中的释放速率是随着纤维中利福平含量的增加而增加的，利福平的含量越大，其释放速率越快。在释放前期，利福平的扩散起主导作用，而在释放后期，其释放行为则是利福平扩散和PLGA（80／20）降解的双重作用结果。适当增加利福平在纤维中的含量（30wt％），则可以获得恒速的释放行为。10．PBS中TEBAC或SDS浓度的增加会在一定程度上使利福平-PLGA（80／20）纤维的释放速率加快，这主要是由于表面活性剂会降低PBS的表面张力，增加水对PLGA（80／20）纤维的浸润能力，从而加快了利福平的扩散速度。

Ultrafine PEG-PLA fibers loaded with both paclitaxel and doxorubicin hydrochloride and their in vitro cytotoxicity

By means of "emulsion-electrospinning", both hydrophobic and hydrophilic drugs, paclitaxel (PTX) and doxorubicin hydrochloride (DOX), were successfully loaded into PEG-PLA nanofiber mats to realize multi-drug delivery. The release behaviors of both the drugs from the same fiber mats were ascribed to their solubility properties and distribution status in the fibers. Due to its high hydrophilicity, DOX was easy to diffuse out from the fibers, and its release rate was always faster than that of hydrophobic PTX. Moreover, the release rate of PTX was accelerated by DOX's release from the same drug-loaded fibers. In vitro cytotoxicity against rat Glioma C6 cells indicated that the dual drug combination showed a higher inhibition and apoptosis against C6 cells than a single drug-loaded system, which suggests the promise for multi-drug delivery on combination therapy.

Syndiotactic 1,2-polybutadiene fibers produced by electrospinning

Syndiotactic 1,2-polybutadiene (s-PB) is a typical thermoplastic elastomer with various applications because of its high reactivity. In the past, it is difficult to form s-PB fibers with a diameter below 10 mu m because of the limitation of the conventional method such as melt spinning. Here, we report for the first time on the production of s-PB nanofibers by using a simple electrospinning method. Ultrafine s-PB fibers without beads were electrospun from s-PB solutions in dichloromethane and characterized by environmental scanning electron microscope (ESEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). At 4 wt.% concentration of s-PB, the average diameter of s-PB was about 130 nm. We found that dichloromethane was a unique suitable solvent for the electrospinning of s-PB fibers, and the structure of syndiotactic was changed through the electrospinning process.