壳聚糖纳米纤维电纺膜体外对肝细胞作用的研究

生物人工肝作为肝功能衰竭的一种有效支持手段,近年来得到很大的进展,但如何长期维持其中肝细胞的活性及功能一直是困扰人们的难题。纳米生物材料的应用为这一问题的解决提供了可能的方案。用静电纺丝的方法将壳聚糖制备成纳米纤维电纺膜,同时采用经典的两步原位胶原酶灌注法分离大鼠肝细胞,观察肝细胞在纳米纤维电纺膜表面的形态,同时检测其活性和功能。肝细胞在壳聚糖纳米纤维电纺膜表面展示了良好的活性,并能与支架材料紧密结合。其尿素合成、蛋白分泌及细胞色素P450的活性均为对照组的1.5~2倍,糖原合成也较对照组有明显增强。壳聚糖纳米纤维电纺膜能促进肝细胞黏附,同时具有良好的生物相容性,从而促进肝细胞的功能,是生物反应器中肝细胞黏附介质的理想材料。     

软组织和硬组织再生过程中的电纺纳米纤维支架

背景：目前，静电纺丝纳米纤维是天然细胞外基质的仿生材料，其包含互连孔隙的三维网络，已成功用作各种组织再生的支架，但目前仍面临着如何将生物材料扩展成三维结构以再现组织微环境的生理、化学以及机械性能的挑战。目的：总结归纳静电纺丝的工艺、原理，探讨由此生产的静电纺丝纳米纤维在皮肤、血管、神经、骨骼、软骨和肌腱/韧带等组织再生中的应用。方法：以“静电纺丝、电纺纳米纤维、电纺纳米纤维支架、组织再生”为中文检索词，“Electrospinning,electrospun nanofibers,electrospun nanofiber scaffolds,tissue regeneration”为英文检索词，检索Google学术、PubMed和中国知网数据库，最终纳入88篇文献进行综述分析。结果与结论：(1)静电纺丝纳米纤维是天然纤维状细胞外基质的仿生材料，并包含互连孔隙的三维网络，在各种组织再生的支架领域中应用较多。(2)多篇文献阐述了电纺纳米支架应用于皮肤、血管、神经、骨骼、软骨和肌腱/韧带组织再生的巨大潜力，为其最终应用于临床疾病治疗，或转化为实际产品进入市场提供了坚实的理论基础。(3)但目...     

静电纺丝小直径人造血管机械力学性质

静电纺丝(电纺)技术是一种制备纤维直径在纳米到微米级人造血管的有效方法.文中综述了静电纺丝小直径人造血管机械力学性质的国内外研究,特别是小直径人造血管在孔隙率、孔径、拉伸性能、爆破强度与顺应性等机械力学性质上的特征,讨论了影响电纺人造血管机械力学性质的主要因素及存在的一些问题.     

静电纺丝纳米纤维组织工程支架的研究进展

背景：静电纺丝纳米纤维具有促进细胞生长的作用。 目的：描述静电纺纳米支架对细胞生长的促进作用以及静电纺纳米支架孔径大小、机械强度缺陷改进的研究进展。 方法：检索数据库为CNKI数字图书馆全文、PubMed数据库2001至2011年有关静电纺丝和组织工程支架的文献。检索关键词为“组织工程,静电纺丝,支架;electrospinning,tissue engineering scaffolds,nanofiber”。 结果与结论：静电纺丝纳米纤维直径、孔径大小及纤维表面对细胞生长行为有重要影响,小孔径静电纺丝纳米纤维支架不利于细胞浸润生长,且用单一电纺技术制备得到的纳米纤维支架机械性能较差,如何增加静电纺丝纳米纤维支架孔径大小以提高细胞的浸润以及提高其机械性能强度,是目前应用研究应解决的问题。     

静电纺丝技术应用于局部治疗领域的研究进展

静电纺丝纳米纤维由于比表面积大、孔隙率高、易添加多种成分等特性,是目前恶性肿瘤局部治疗领域的研究热点之一.因为电纺丝技术的多功能性,通过调整电纺纤维的结构和载药方式,可以满足不同的辅助治疗需求.本文从不同的电纺丝功能设计阐述了电纺丝纳米纤维膜在局部治疗领域的研究进展,并展望其发展前景.     

PCL基电纺纤维膜的抑菌、相容及降解性能研究﹡

目的探讨不同材料组成对PCL基电纺纤维膜的表面形貌、亲水性能、抑菌性能、生物相容性、屏蔽和降解性能的影响。方法电纺丝法制备了PCL、PCL/甲硝唑、PCL/明胶/甲硝唑以及PCL/明胶/甲硝唑/醋酸纳米纤维膜,对应P0,P30,PG30及PGH30。扫描电镜(SEM)观察不同膜的表面结构。通过测量载药膜周围抑菌圈的直径来表征膜的抗菌性能。四唑盐比色法(MTT)测试测试细胞毒性。通过兔皮下埋植,伊红苏木素(H&E)染色切片法观察不同膜的组织相容性,降解性能及细胞屏蔽性能。结果甲硝唑的引入赋予膜良好的抑菌性能。明胶引入显著提高了膜的组织相容性及降解速率。电纺液中微量醋酸(0.1%v/v聚合物溶液)能够有效提高电纺液的均一性,从而得到结构及性能稳定的纤维膜。高药物含量及微量醋酸的加入对于膜的细胞及组织相容性均无明显副作用。P0及P30在24周内均能够维持对成纤维细胞的屏蔽作用,PGH30能够维持8周,而PG30的细胞屏蔽期小于8周。结论不同组分对纳米纤维膜的结构和性能具有不同影响。本研究将为设计广泛应用于骨科疾病治疗的膜材料奠定基础。     

静电纺丝在组织工程学中的应用进展

组织工程学是一个综合性学科领域,它涵盖了医学、生物医学工程、恢复或再生损伤组织和器官功能等领域。支架、细胞和生物分子是组织工程的三大基本支柱。静电纺丝是通过静电高压技术对高分子材料进行电纺,获得的电纺纤维即为细胞支架。不同的高分子材料可以获得不同性质的细胞支架。该文对电纺纤维在组织工程中的应用进展,其中包含在皮肤、血管、神经、骨、软骨方向的应用加以综述。     

抗菌型纳米纤维膜的释药及生物相容性研究

目的探讨药物含量对抗菌型纳米纤维膜释药行为、抑菌性能及生物相容性及降解性能的影响。方法电纺制备聚己内酯(PCL)/甲硝唑(MNA)纳米纤维膜(MNA占PCL的质量比为0、1%、5%、10%、20%、30%及40 wt%),对应编号P0、P1、P5、P10、P20、P30及P40。通过高效液相色谱(HPLC)检测不同载药量样品不同时间段的药物释放量。通过测量载药膜周围抑菌圈的直径来表征膜的抗菌性能。四唑盐比色法(MTT)测试测试细胞毒性。细胞计数Kit-8法(CCK-8)评价小鼠成纤维细胞L929在不同膜表面粘附及增殖情况。通过兔皮下埋植,伊红苏木素(HE)染色切片及扫描电镜(SEM)观察不同膜的组织相容性及降解性能。结果药物释放具有1周内突释,后逐渐缓释的特点。药物含量5%以上样品1天后开始呈现抑菌圈,且持续抑菌时间达30天。随药物含量增加,抑菌圈直径增加。载药膜具有良好的细胞相容性,其中P30的细胞相容性最好。加载药物能够提高组织相容性及降解速率。结论 PCL/MNA纳米纤维膜具有良好的抑菌性能及生物相容性。P30的综合性能最佳。     

静电纺丝技术在创伤敷料方面的研究进展

静电纺丝技术制备的纳米纤维膜具有较高的比表面积、多孔性以及易于实现表面功能化等特点,已成为纳米技术研究领域的一个新热点,目前,静纺纤维膜作为一种高端的功能性敷料已受到广泛的重视。本文对静纺纤维膜作为医用敷料进行简述,旨在为静电纺丝技术在创伤敷料方面的应用提供依据。     

静电纺纳米纤维基组织工程大孔支架的研究进展

静电纺丝作为一种纳米纤维支架的仿生构建方法,已在组织工程和再生医学领域中得到越来越多的应用和关注。但是,静电纺支架的主要问题是密集排列的纳米纤维之间的空隙很小,阻碍细胞的长入和三维(3 D)组织的形成。为了解决这一问题,近年来已发展了许多用于扩大静电纺纳米纤维支架孔尺寸的制备方法。首先概述组织工程支架中大孔对细胞行为的影响,然后对静电纺纳米纤维3 D大孔支架的制备方法和技术研究进展进行综述,讨论这些3 D大孔支架促进细胞长入的效果,最后对静电纺3 D大孔支架在组织工程中应用的主要挑战和前景,提出了看法。     

Diverse release behaviors of water-soluble bioactive substances from fibrous membranes prepared by emulsion and suspension electrospinning

Time-programmed release behaviors of different bioactive substances, enough mechanical properties and good biocompatibility of the scaffold play an important role in vascular tissue regeneration. In this paper, ultrafine fibers with diverse release behaviors were prepared by emulsion or suspension electrospinning from poly(L-lactide-co-glycolide) (PLGA) or poly(ethylene glycol)-b-poly(L-lactide-co-caprolactone) (PELCL), designated as E-PLGA, EH-PLGA, and EH-PELCL, respectively. Chitosan hydrogel was in situ encapsulated in the fibers by suspension electrospinning to provide the carriers for water-soluble bio-additives. To determine the potential applications in vascular tissue engineering areas, morphology and structure of the obtained fibers, the hydrophilicity, mechanical properties, release behaviors, and cytobiocompatibility of the electrospun membranes were investigated. Scanning electron micrographs showed that the diameter of the fibers was in the range of 150–1380?nm. The hydrogel was encapsulated and distributed discretely into the fibers, which was demonstrated visually by transmission electron micrographs and confocal laser scanning microscopy images. All the membranes exhibited good hydrophilicity and excellent mechanical properties, comparable with human coronary artery. The encapsulation efficiency of a protein model, horseradish peroxidase was up to 70%. Diverse release behaviors were obtained and EH-PELCL showed faster release rate than EH-PLGA and E-PLGA fibers. The fibroblast could adhere, spread, and proliferate on the membranes in good condition showed good cytobiocompatibility of the membranes. This experiment proved that the obtained E-PLGA, EH-PLGA, and EH-PELCL electrospun fibrous scaffolds with enough mechanical properties, different release rates of protein drugs and good cytobiocompatibility could be used as vascular scaffolds for further study.     

Preparation and characterization of electrospun PLGA/gelatin nanofibers as a drug delivery system by emulsion electrospinning

Novel biocompatible poly(lactide-co-glycolide) (PLGA) nanofiber mats with favorable biocompatibility and good mechanical strength were prepared, which could serve as an innovative type of tissue engineering scaffold or an ideal controllable drug delivery system. Both hydrophobic and hydrophilic drugs, Cefradine and 5-fluorouracil were successfully loaded into PLGA nanofiber mats by emulsion electrospinning. The natural bioactive protein gelatin (GE) was incorporated into the nanofiber mats to improve the surface properties of the materials for cell adhesion. Nanofibrous scaffolds were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, contact angle and tensile measurements. Emulsion electrospun fibers with GE had perfect hydrophilic and good mechanical property. The in vitro release test showed thedrugs released from emulsion electrospun fibers, which achieved lower burst release. The cells cytotoxicity experiment indicated that emulsion electrospun fibers were less toxic and tended to promote fibroblasts cells attachment and proliferation, which implied that the electrospun fibers had promising potential application in tissue engineering or drug delivery.     

Coaxial electrospun zein nanofibrous membrane for sustained release

Zein nanofibrous membranes for sustained release have been prepared by coaxial electrospinning. Core-sheath structure has been successfully fabricated using zein as both the core and sheath component. Impact of solvent and solution concentration on the morphology of the resulting fibers was investigated. Allyltriphenylphosphonium bromide was used as a model drug to test the sustained release effect. The sustained release profile and the antimicrobial activity of the resulting membranes were investigated and compared with that of the single fluid electrospinning of zein/drug blended membrane. The ratio of the inner and outer feeding rates was found to influence the encapsulation of drugs, and in turn affect the sustained release effect of the resulting membranes. The coaxial electrospinning membrane can remarkably suppress the initial burst release of drugs by giving a releasing amount of 15% in the first 1?h when the inner/outer ratio was larger than 1:2. This drug-loaded zein membrane with preferable sustained release effect can be applied in many fields such as wound healing and packaging sector.     

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.     

Encapsulation and Controlled Release of Heparin from Electrospun Poly(L-Lactide-co-ε-Caprolactone) Nanofibers

Poly(L-lactide-co-ε-caprolactone) nanofibers with heparin incorporated were successfully fabricated by coaxial electrospinning. The morphologies of electrospun nanofibers were studied by scanning electron microscopy (SEM), and a significant decrease in fiber diameter was observed with increasing heparin concentration. The transmission electron microscopy (TEM) images indicated that coaxial electrospinning could generate core–shell structure nanofibers which have the potential to encapsulate drugs (heparin in this study) into the core part of nanofibers. Approximately 80% of the encapsulated heparin was sustainedly and stably released from the fibrous composite in 14 days by a diffusion/erosion coupled mechanism. The release behavior of heparin from blend electrospun nanofibers was also studied and showed an obvious burst release in the initial stage. An in vitro proliferation test was conducted to study the effect of heparin released from nanofibers, and the results suggest that the heparin maintains its bioactivity after encapsulating with and delivery through coaxially electrospun fibers.     

Enhanced osteogenesis and angiogenesis by PCL/chitosan/Sr-doped calcium phosphate electrospun nanocomposite membrane for guided bone regeneration

Abstract

Membranes play pivotal role in guided bone regeneration (GBR) technique for reconstruction alveolar bone. GBR membrane that is able to stimulate both osteogenic and angiogenic differentiation of cells may be more effective in clinic practice. Herein, we fabricated the Sr-doped calcium phosphate/polycaprolactone/chitosan (Sr-CaP/PCL/CS) nanohybrid fibrous membrane by incorporating 20?wt% bioactive Sr-CaP nanoparticles into PCL/CS matrix via one-step electrospinning method, in order to endow the membrane with stimulation of osteogenesis and angiogenesis. The physicochemical properties, mechanical properties, Sr²⁺ release behavior, and the membrane stimulate bone mesenchymal stem cell (BMSCs) differentiation were evaluated in comparison with PCL/CS and CaP/PCL/CS membranes. The SEM images revealed that the nanocomposite membrane mimicked the extracellular matrix structure. The release curve presented a 28-day long continuous release of Sr²⁺ and concentration which was certified in an optimal range for positive biological effects at each timepoint. The in vitro cell culture experiments certified that the Sr-CaP/PCL/CS membrane enjoyed excellent biocompatibility and remarkably promoted rat bone mesenchymal stem cell (BMSCs) adhesion and proliferation. In terms of osteogenic differentiation, BMSCs seeded on the Sr-CaP/PCL/CS membrane showed a higher ALP activity level and a better matrix mineralization. What’s more, the synergism of the Sr²⁺ and CaP from the Sr-CaP/PCL/CS membrane enhanced BMSCs angiogenic differentiation, herein resulting in the largest VEGF secretion amount. Consequently, the Sr-CaP/PCL/CS nanohybrid electrospun membrane has promising applications in GBR.     

Preparation and Drug-Delivery Potential of Metronidazole-Loaded PELA Tri-block Co-polymeric Electrospun Membranes

The aim of this study was to investigate the potential of poly(ethylene glycol-co-lactide) (PELA tri-block with a segmental sequence of PLA–PEG–PLA) electrospun membranes as drug-delivery vehicles using metronidazole as a model drug. PELA membranes with smooth surfaces and no bead defects were electrospun from polymer solutions containing 20% (w/v) PELA in 8:2 N,N-dimethyl formamide (DMF)/acetone. The morphology of the drug-loaded electrospun membranes was influenced by electrospinning parameters such as the flow rate and voltages during preparation. Metronidazole could be released from the electrospun membranes and was characterized by an initial burst effect. Higher voltages led to faster release rates, while an increase in the flow rate decreased the drug release. The incorporation of metronidazole into the electrospun membranes decreased their surface hydrophilicity. The amount of drug released from the electrospun membranes was effective in inhibiting microbial growth. Cell adhesion on the PELA membranes with or without drug was less than that on the homo-polymeric PDLLA membranes. Proliferation of L929 mouse fibroblasts on the PELA membranes was observed. This study confirms the potential of metronidazole-loaded PELA biodegradable electrospun membranes for optimizing the clinical therapy of post-surgical adhesions and infections.     

Functionalization of electrospun poly(caprolactone) fibers for pH-controlled delivery of doxorubicin hydrochloride

Functionalized electrospun polymer fibers are a promising candidate for controlled delivery of chemotherapeutic drugs to improve the therapeutic efficacy and to reduce the potential toxic effects by delivering the drug at a rate governed by the physiological need of the site of action. In this study, poly(caprolactone) (PCL) fibers were fabricated by electrospinning, followed by hydrolyzation to introduce functional groups on the fiber surface. Characterization studies were performed on these functionalized fibers using X-ray photoelectron spectroscopy, scanning electron microscopy, and Toluidine Blue O dye assay. The pH-sensitivity of the functional groups on the fiber surface and doxorubicin hydrochloride was utilized to bind the drug electrostatically to these functionalized PCL fibers. The effect of pH on drug loading and release kinetics was investigated. Results indicate successful electrostatic binding of the drug to functionalized electrospun fibers and a high drug payload. The drug delivery response can be modulated by introduction of suitable stimuli (pH).