基于静电纺丝技术的PLGA载药纳米纤维膜的制备工艺

同轴静电纺丝法制备的聚乳酸-乙醇酸(PLGA)纳米纤维具有良好的生物相容性和生物可降解性, 加之其高孔隙率和高透氧率, 使其能成为优良的药物载体。本文初步摸索了PLGA的同轴静电纺丝的工艺条件, 并通过同轴静电纺丝法制备了PLGA载氟比洛芬酯(FA)的纳米纤维膜, 应用扫描电子显微镜、红外光谱分析观察纤维的表观形貌并确定其微观结构。重点探究了不同溶剂配比的混合溶剂对载药纤维膜药物释放性能影响。研究结果表明在U⁺为+15.00kV, U^-为-2.50kV, 接受距离为15cm, 壳层推进速度为0.4mm/min, 芯层推进速度为0.1mm/min进行静电纺丝时, 所制备的PLGA(壳)/PVP+FA(核)复合载药纤维膜壳核结构良好, 且成功载了约0.5%的FA。当改变壳层混合溶剂(DCM和DMF)和芯层混合溶剂(无水乙醇和DMF)体积比时, 纤维直径会随着DMF的减少而增大。     

同轴静电纺丝素蛋白纤维支架的制备及结构性能表征

以再生丝素蛋白水溶液为皮层纺丝液,去离子水为芯层纺丝液,探讨了同轴静电纺制备丝素蛋白组织工程支架材料的最佳工艺参数。结果表明,随着皮层纺丝液质量分数的提高,支架材料的表观形貌逐渐变好;当皮层纺丝液的质量分数为39%(w)、流速为1.2 m L/h,芯层纺丝液流速为0.3 m L/h时,可制备出表观形貌好、纤维粗细均匀且具有稳定皮芯结构的支架材料。文章探索得到的同轴静电纺丝工艺可用于载药组织工程支架材料的制备,并在组织工程修复领域具有良好的应用前景。     

冷冻干燥工艺对聚乳酸多孔支架孔结构的影响

以聚乳酸为原料,冰粒子为致孔剂,采用正压渗流-冷冻干燥法制备聚乳酸多孔支架,研究不同冷冻干燥工艺对多孔支架孔结构的影响,对多孔支架进行宏观和微观形貌分析、孔隙率和收缩率测试,确定最佳制孔条件。研究结果表明,冷冻干燥温度在-40℃以上,聚乳酸多孔支架外形良好,但孔的均匀性、连通性明显下降;冷冻干燥温度在-50℃时,能够有效提高冷冻干燥效率,孔的均匀性、孔隙率略有下降;冷冻干燥温度在聚乳酸-氯仿-冰体系共熔点以下,制备出多孔支架孔结构均匀、连通度良好、孔隙率高。     

聚乳酸⁃羟基乙酸共聚物涂层对聚乳酸3D打印支架的性能影响

通过熔融沉积（FDM）三维（3D）打印技术制备了61.7 %孔隙率和良好连通性的3D多孔聚乳酸（PLA）支架,使用浸涂法对PLA支架表面涂覆浓度分别为2 %、4 %、6 %、8 %的聚乳酸⁃羟基乙酸共聚物（PLGA）涂层,获得了不同浓度涂层的PLA/PLGA复合支架。通过扫描电子显微镜（SEM）、接触角测量仪、万能试验机和细胞计数试剂盒⁃8方法等测试手段,探究了不同浓度PLGA涂层对PLA支架的断面微观形貌、支架表面亲水性、力学强度以及细胞在支架上增殖活性等性能的影响规律。结果表明,与未经包裹的PLA支架相比,包裹PLGA的PLA支架表面接触角显著减小,PLGA的质量分数为6 %时接触角最小为（64.7±1.1） °;接种后经24 h培养PLA/PLGA支架表面细胞活性较纯PLA支架显著增强。     

乙醇后处理对静电纺聚乳酸非织造网的影响

以六氟异丙醇(HFIP)为溶剂,通过静电纺丝制得聚乳酸(PLA)纳米纤维非织造网,纤维平均直径246nm,经75%乙醇处理后,纤维之间出现了粘连现象。乙醇后处理对PLA纳米纤维非织造网红外光谱影响不大;而通过热分析计算得到的PLA纤维在处理前、纯乙醇处理后和75%乙醇处理后的结晶度分别是28.3%、33.1%和34.1%,这说明乙醇后处理改变了PLA纤维的分子聚集态结构;另外玻璃化温度、结晶温度和熔融温度都有所增大,而热分解温度从处理前的375.4℃下降到处理后的360.3℃。这些变化说明,纯乙醇和75%乙醇后处理都对PLA纤维有明显的影响,特别是对形态、结晶度和热性能参数的影响较大。     

静电纺再生丝素纳米纤维的结构与性能

静电纺丝获得的丝素纳米级纤维可作为细胞培养支架,用于纺丝工艺及后处理能改变丝素微细结构,影响其水溶性和力学性能。本文采用XRD、FTIR、固态13CNMR和DSC研究了不同工艺下丝素纳米纤维及经甲醇处理后的微细结构,比较了不同微细结构下的水溶性和力学性能。结果表明,电纺丝的微细结构受纺丝工艺影响,高电压、纺丝液中丝素质量分数大时纺得的电纺丝结晶度高,经甲醇处理后,β化程度提高;w(丝素)=11%、15%时制备的电纺丝断裂强度分别为8.5、11.9 cN/mm;w(丝素)=11%、19%,水溶性由51.2%下降到43.3%;w(丝素)=19%、电压32 kV制得的电纺丝甲醇处理前后水溶性从43.3%下降到6.6%,说明丝素纳米纤维结晶度提高,强度增加、水溶性下降,满足了细胞支架的要求。     

碳纤维增强聚合物组织工程支架的制备及表征

以碳纤维（CF）作为增强材料,将CF有序排列于聚乳酸羟基乙酸（PLGA）多孔结构中,制备性能优良的CF/PLGA复合支架,并对其力学性能及细胞生物学性能进行表征.对增强体CF进行有序排列以提高支架的力学性能,扫描电子显微镜（SEM）观察CF/PLGA复合支架的微观形貌,可以看出CF在聚合物基体内部是呈有序结构并且二者结合情况良好.为了提高CF的生物相容性,利用对氨基苯甲酸对CF进行表面修饰,细胞生长在支架上的SEM照片反映了成纤维细胞对PLGA及CF/PLGA复合支架的黏附性能良好;通过细胞毒性测试,发现表面修饰的CF对细胞的生长没有负面作用,且在一定程度上促进了细胞的生长.研究结果表明,制备的CF/PLGA支架具有良好的力学性能和生物相容性,在骨组织工程支架的应用中具有一定的潜力.     

二氧化硅膜的电纺合成工艺研究

以正硅酸四乙酯(TEOS)为硅源,聚乙烯吡咯烷酮(PVP)为模板剂,将上述两物质溶解于乙醇中制备电纺前驱体溶液,通过静电纺丝技术及后续煅烧处理,制备二氧化硅纤维膜。研究电压、纺丝距离、喷射速度、针头大小及针头平移速度对二氧化硅纤维形貌结构的影响。通过综合热分析法(TG-DSC)、X射线粉末衍射(XRD)、扫描电镜(SEM)对产物进行表征。当纺丝参数为:电压12KV、纺丝距离20cm、喷射速度0.3mm/s、针头内径0.3mm、针头平移速度200mm/min时,获得的纳米纤维具有良好的形貌。     

熔体静电纺丝直写技术在组织工程中的应用进展

熔体静电纺丝直写技术以其纤维直径、沉积形貌可控性高及无溶剂残留等优势,为高强度复杂形貌可控仿生组织工程（TE）支架的制备提供了巨大的空间,成为近年来的研究热点。本文首先简述了熔体静电纺丝直写技术相对于各类其他TE支架制备方法的优势;其次从工艺调控方面综述了熔体静电纺丝直写技术的工艺研究进展,并总结了实现复杂可控形貌TE支架的调控方法;随后从支架材料、形貌表征和细胞培养效果等方面综述了熔体静电纺丝直写技术的TE应用进展,并概括了该技术制备的TE拓扑结构支架的种类及特点;最后指出熔体静电纺丝直写技术具有广阔的研究前景,且该技术应以制备仿生、材料多样化以及复合支架为研究重点。     

包埋PLGA微球的可控释壳聚糖支架材料的研究

为解决组织工程支架材料内部营养供应不足的问题,将营养物质包埋在聚合物微球内再植入支架,通过微球内营养物质的控制释放保持支架内部营养物质浓度的持续均匀性。以牛血清白蛋白(BSA)为模型蛋白,乳酸-羟基乙酸共聚物(PLGA)为外包被材料,采用复乳法(w/o/w)制备聚合物微球,然后将该微球与壳聚糖溶液混合,冻干形成支架。以BCA法检测载药微球自身的释放情况以及其植入到支架后的释放情况,通过扫描电镜观察载药微球的结构以及其植入支架材料后结构变化。结果表明,微球形态圆整,粒径范围在27～55μm之间。壳聚糖支架呈多孔状结构,1%壳聚糖支架孔隙率、吸水率和降解率分别为(92.99±2.51)%、(89.66±0.66)%和(73.77±3.21)%。体外释放显示:微球可以持续释放所包埋的蛋白,突释较小,168h后PLGA微球的累积释放量为(20.24±0.83)%。电镜照片显示,微球植入支架后,与支架结合紧密,微球结构没有发生明显改变。168h后支架内部蛋白浓度为(11.44±1.81)×10-2mg·mL-1。相比传统靠外部培养基自由扩散到支架内部为支架内细胞供养的方法,营养物质或细胞因子包埋在控释微球中并与支架材料复合成可控释支架,可以长时间维持支架中这些因子的浓度均匀,从而为组织工程提供理想的支架材料。     

Hemocompatible polyurethane/gelatin-heparin nanofibrous scaffolds formed by a bi-layer electrospinning technique as potential artificial blood vessels

In this paper, a scaffold, which mimics the morphology and mechanical properties of a native blood vessel is reported. The scaffold was prepared by sequential bi-layer electrospinning on a rotating mandrel-type collector. The tubular scaffolds (inner diameter 4 mm, length 3 cm) are composed of a polyurethane (PU) fibrous outer-layer and a gelatin-heparin fibrous inner-layer. They were fabricated by electrospinning technology, which enables control of the composition, structure, and mechanical properties of the scaffolds. The microstructure, fiber morphology and mechanical properties of the scaffolds were examined by means of scanning electron microscopy (SEM) and tensile tests. The PU/gelatin-heparin tubular scaffolds have a porous structure. The scaffolds achieved a breaking strength (3.7±0.13 MPa) and an elongation at break (110±8%) that are appropriate for artificial blood vessels. When the scaffolds were immersed in water for 1 h, the breaking strength decreased slightly to 2.2±0.3 MPa, but the elongation at break increased to 145±21%. In platelet adhesion tests the gelatin-heparin fibrous scaffolds showed a significant suppression of platelet adhesion. Heparin was released from the scaffolds at a fairly uniform rate during the period of 2^nd day to 9^th day. The scaffolds are expected to mimic the complex matrix structure of native arteries, and to have good biocompatibility as an artificial blood vessel owing to the heparin release.     

A biomimetic mesoporous silica–polymer composite scaffold for bone tissue engineering

A biomimetic organic–inorganic composite system comprising of microspheres fabricated from combination of a biodegradable polymer poly(lactide-co-glycolide) (PLGA) and bioactive mesoporous silica (SBA-15) has been developed through sintering technique for bone regeneration applications. The morphological and structural properties of the SBA-15/PLGA composite scaffold were evaluated using electron microscopy and fourier transform infrared spectroscopy and the results showed spherical morphology and composite nature. The presence of mesopores in the silica was confirmed through nitrogen adsorption–desorption isotherms. The surface area and pore size of mesoporous silica were found to be 792 m² g^?1 and 3.7 nm, respectively. The thermal characteristics of the SBA-15/PLGA composites studied using thermogravimetry analysis shows a weight loss of around 80% with the degradation occurring at 324?°C. The prepared scaffold is also found to support the adhesion and proliferation of osteoblast cells. The expression of specific bone markers is significantly enhanced in the SBA-15/PLGA composite scaffold when compared with the pristine polymeric scaffold indicating the positive effect of mesoporous silica. Hence, these SBA-15/PLGA composite scaffolds can be explored further for bone regeneration applications.     

Hydrolytic degradation and cytotoxicity of poly(lactic-co-glycolic acid)/multiwalled carbon nanotubes for bone regeneration

Biodegradable poly(l -lactide-co-glycolide) (PLGA)/multiwalled carbon nanotubes (MWCNTs) scaffolds produced by thermally induced phase separation (TIPS) are studied for bone regeneration. Their magnetic properties, cytotoxicity, and in vitro degradation are investigated. Certain properties are analyzed at 37 °C over 16 weeks in phosphate buffer saline (PBS) solution, as a function of degradation time: morphology, mass loss, pH value of PBS, and thermal behavior. The presence of small quantities of nanotubes in the scaffolds, ≤0.5 wt %, leads to a weak magnetic response although the PLGA was diamagnetic. The incorporation of MWCNTs in the scaffolds generated a morphology and a very different process of in vitro degradation than might be expected in a PLGA scaffold. The in vitro degradation process started on week 13 and rapidly advanced, although the structural integrity of the scaffolds was maintained and no collapse of the structure occurred. Cytotoxicity tests on the samples showed cytotoxicity behavior at concentrations of over 0.3 wt % MWCNTs. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48439.     

A facile preparation of highly interconnected macroporous poly(d,l-lactic acid-co-glycolic acid) (PLGA) scaffolds by liquid-liquid phase separation of a PLGA-dioxane-water ternary system

Regular and highly interconnected macroporous scaffolds ranging in size from 50 to 150 μm were fabricated from poly(d,l-lactic acid-co-glycolic acid) (PLGA)-dioxane-water ternary systems via thermally induced phase separation (TIPS) without any surfactant or other additives. The effect on scaffold morphology of processing parameters including quenching temperature, polymer concentration, solvent composition and molecular weight, was investigated as a function of quenching time. The cloud-point temperature of the polymer solution was found to depend on polymer concentration, solvent composition, and polymer molecular weight. The water content in the solvent mixture had the greatest effect on the cloud-point temperature. The optimal quenching temperature for preparing macroporous inter-connected scaffolds from a 9 wt% PLGA solution (dioxane-water=87/13, by wt) was less than −7 °C. In low viscosity PLGA solutions, sedimentation of the polymer rich phase occurred due to the segregation of the separated phases under gravity. This led to the formation of scaffolds with irregular and closed pores.     

Formation of porous PLGA scaffolds by a combining method of thermally induced phase separation and porogen leaching

A novel method for the fabrication of porous poly(L -lactide-co-glycolide) (PLGA) scaffolds by combining thermally induced phase separation and porogen leaching is presented in this article. Big pores with about 75–400 μm diameters in the obtained scaffolds were generated by the porogen, sucrose particles, while small pores with diameters less than 20 μm induced via phase separation. Extraction of the solvent, chloroform by ethanol at cool temperatures could reduce the scaffold toxicity. Effects of PLGA concentration, freezing temperature, volume fraction of porogen, and introduction of β-tricalcium phosphate (β-TCP) on morphology, porosity, and compressive properties of the scaffolds were systematically discussed. Results showed that the size of small pores decreased by decreasing the polymer concentration and reducing the freezing temperature, whereas the interconnectivity of the scaffolds was improved by increasing the porogen fraction. The compressive modulus and strength were significantly lowered by increasing the scaffold porosity, that is, by increasing porogen fraction, or decreasing the polymer concentration, or reducing the freezing temperature. Addition of β-TCP into the scaffolds did not influence the compressive modulus significantly but tended to decrease the compressive strength. The obtained scaffolds with diverse pore sizes would be potentially used in bone tissue engineering. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

骨组织工程用PLGA多孔支架的制备及细胞毒性研究

制备能在骨组织工程研究中应用,并具有良好孔隙结构的块状聚（D,L-乳酸-CO-乙醇酸）（PLGA）多孔支架,探索出以冰粒子作为致孔剂,采用粒子滤出方法结合冷冻干燥工艺制备多孔支架的方法.首先将冰颗粒加入预冻的PLGA氯仿溶液中混合均匀,然后把混合物置于液氮中深度冷冻后冷冻干燥,制得多孔支架.对支架孔隙结构分析表明,该工艺制备的多孔支架无致孔剂残留、三维结构良好、孔径与孔隙可通过改变冰粒子的粒径和质量分数来控制;细胞毒性实验表明该多孔支架毒性在0～1级,可作为骨组织工程研究用多孔支架.     

PLGA/nHA hybrid nanofiber scaffold as a nanocargo carrier of insulin for accelerating bone tissue regeneration

The development of tissue engineering in the field of orthopedic surgery is booming. Two fields of research in particular have emerged: approaches for tailoring the surface properties of implantable materials with osteoinductive factors as well as evaluation of the response of osteogenic cells to these fabricated implanted materials (hybrid material). In the present study, we chemically grafted insulin onto the surface of hydroxyapatite nanorods (nHA). The insulin-grafted nHAs (nHA-I) were dispersed into poly(lactide-co-glycolide) (PLGA) polymer solution, which was electrospun to prepare PLGA/nHA-I composite nanofiber scaffolds. The morphology of the electrospun nanofiber scaffolds was assessed by field emission scanning electron microscopy (FESEM). After extensive characterization of the PLGA/nHA-I and PLGA/nHA composite nanofiber scaffolds by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectrometry (EDS), and transmission electron microscopy (TEM), the PLGA/nHA-I and PLGA/nHA (used as control) composite nanofiber scaffolds were subjected to cell studies. The results obtained from cell adhesion, alizarin red staining, and Von Kossa assay suggested that the PLGA/nHA-I composite nanofiber scaffold has enhanced osteoblastic cell growth, as more cells were proliferated and differentiated. The fact that insulin enhanced osteoblastic cell proliferation will open new possibilities for the development of artificial scaffolds for bone tissue regeneration.     

PLGA/SF blend scaffolds modified with plasmid complexes for enhancing proliferation of endothelial cells

Biomimetic scaffolds have been investigated for vascular tissue engineering for many years. However, the design of an ideal biodegradable vascular scaffold is still in progress. The optimization of poly(lactide-co-glycolide)/silk fibroin (PLGA/SF) blend composition was performed to provide the designed scaffolds with adequate mechanical properties and favorable biocompatibility for the intended application. By systematically varying the weight ratio of PLGA and SF, we could control fiber diameter and hydrophilicity as well as mechanical properties of the fibrous scaffolds. These scaffolds with a weight ratio of PLGA/SF at 70/30 exhibited excellent performance, such as tensile strength of 1.5 ± 0.1 MPa, and elongation at break of 77.4 ± 6.4%. Therefore, PLGA/SF scaffold with a weight ratio of 70/30 was chose as the matrix because it matches at best the mechanical demands for application in vascular tissue engineering. In order to promote the endothelialization of electrospun scaffolds, we used pEGFP-ZNF580 plasmid (pZNF580) complexes to modify the electrospun scaffolds by electrospraying technique. pZNF580 complexes were prepared from pZNF580 and microparticles (MPs) of amphiphilic copolymer methoxy-poly(ethylene glycol)-block-poly(3(S)-methyl-2,5-morpholinedione-co-glycolide)-graft-polyethyleneimine. Negatively charged PLGA/SF fibers adsorbed the positively charged MPs via physical deposition and electrostatic force. Scanning electron microscope image indicated the forming of composite scaffold and MPs did not change fiber’s shape and 3-D structure. Cell culture experiments demonstrated that the scaffolds modified with MPs/pZNF580 complexes could promote human umbilical vein endothelial cell growth and inhibit human umbilical artery smooth muscle cell proliferation. Our results indicated that the composite scaffolds with MPs/pZNF580 complexes could be used as a potential scaffold for vascular tissue engineering.