高分子微球在三维细胞培养领域的应用进展

三维细胞培养能够模拟细胞在体内的形态和功能，因此成为新兴的细胞培养技术。在不同的三维细胞培养方法中，微球支架为模拟微环境下的三维空间细胞黏附、增殖和细胞相互作用提供了一种有价值的工具。其中，基于可降解高分子的微球支架因优异的生物相容性和生物降解性得到了广泛的研究。综述了基于可降解高分子微球支架的最新进展，包括天然高分子和合成高分子以及在三维细胞培养方面的应用，探讨了高分子微球支架的应用局限性和潜在的解决方法，并指明了其未来发展方向。     

生物玻璃/聚乳酸多孔微球的制备及其作为细胞载体的研究

具有大孔结构的多孔微球既可以在体外扩增细胞, 还可以作为细胞的传输工具, 通过注射的方式把细胞输送到需要修复的组织部位。生物玻璃虽然生物活性良好, 但难以直接制备成大孔结构的微载体。因此, 本研究将生物玻璃(BG)与聚乳酸(PLA)高分子复合, 通过复乳法制备了一种含生物玻璃的多孔微球细胞微载体。并通过扫描电镜(SEM)、热重分析(TGA)、电感耦合等离子体发射光谱仪(ICP-OES)等方法研究分析了微球的形貌、组成和离子释放。通过细胞实验, 证明细胞可以在微球的多孔结构中粘附和增殖, 并且生物玻璃可以促进细胞增殖, 在组织工程中具有潜在应用。     

微米级多孔聚苯乙烯-二乙烯苯微球的制备、改性及应用综述

微米级多孔聚合物微球作为一种新型功能材料,是目前高分子材料领域的一大研究热点。微球粒径通常在1μm至数百微米,干燥状态下内部有几埃甚至几千埃的孔隙,具有球形度好、比表面积大、骨架密度低、吸附性强、力学强度高、与不同极性的有机溶剂兼容性好等诸多优点,在生物医学、分析化学、环境保护、催化剂载体以及电子产品等领域中有十分广阔的应用前景。其中多孔聚苯乙烯-二乙烯苯微球除了具有高分子微球的一般特点外,还有物理及化学稳定性好、热稳定性好、生产成本低、工业应用前景广等优点,同时微球的苯环反应活性高,易于进行一系列的功能化反应,从而扩大其应用领域。基于上述优点,多孔聚苯乙烯-二乙烯苯微球是目前应用最多的多孔聚合物微球。广阔的应用前景和市场,使得多孔聚苯乙烯-二乙烯苯微球的制备和功能化成为国内外学者研究的热点,并取得了令人瞩目的发展。在过去的几十年中逐渐出现了多种微球制备方法。悬浮聚合法是制备多孔聚苯乙烯-二乙烯苯微球的传统方法,其操作简单,产物后处理方便,但是得到的微球粒径呈多分散性。种子溶胀法被普遍认为是制备单分散多孔聚苯乙烯-二乙烯苯微球较好的方法,该方法在制备表面功能化、单分散大粒径的聚苯乙烯-二乙烯苯微球方面具有明显优势。沉淀聚合法也可以用来制备单分散的微球,但是该方法制备的微球交联度低、产量低,而且不易制备具有多孔结构的功能性微球。近几年利用微工程乳化技术制备微球的报道越来越多,包括微孔膜/微通道乳化法和微流控技术。这类方法制备的聚苯乙烯-二乙烯苯微球单分散性良好,粒径、孔径等重现性好,为制备多孔聚合物微球开辟了新的方向。与此同时很多研究者致力于功能性多孔聚苯乙烯-二乙烯苯微球的开发,通过在微球上引入各种功能基团改善微球的疏水性、溶解性和生物亲和性等,制得的不同特性的微球可应用于高效色谱填料、催化剂载体、生物医学、吸附剂等领域。本文首次详尽地分析和综述了微米级多孔聚苯乙烯-二乙烯苯微球的制备方法和改性方法,讨论了影响微球孔径及孔分布的重要因素,并总结了该类微球近几年的应用研究状况,最后对多孔聚苯乙烯-二乙烯苯微球的发展前景进行了展望。     

磁性高分子微球的制备方法与发展趋势

磁性高分子微球作为一种新型功能材料,兼具高分子微球的众多特性和磁响应性,在靶向药物、细胞分离、细胞标记、固定化酶和生物传感器等领域有着广阔的应用前景.综述了各类磁性高分子微球的制备方法及各自的优缺点,概述了磁性高分子微球的重要参数及表征方法,预测了高分子微球研究工作的趋势.     

生物高分子磁性微球的研究进展

磁性高分子微球是近二十年来研究的一类新型功能材料。拟从生物高分子磁性微球的制备、结构、性能和应用等几个方面综述近年来国内外有关磁性高分子微球的研究状况。     

空心/多孔微球制备技术研究进展

综述了聚合物多孔微球和空心微球的制备方法及其相应的成孔机理。空心微球的制备以模板法为主,而多孔微球的制备则以种子溶胀法和致孔剂法为主。这些方法各有优缺点,根据材料的用途选择相应的制备方法,才能得到性能理想的中空或多孔微球。同时,讨论了多孔微球和空心微球制备中存在的问题及制备方法的选择。     

超临界CO2辅助制备PHAs载药微球研究概况

聚羟基烷酸酯(PHAs)是一种具有良好生物相容性的可降解生物材料。主要介绍了超临界二氧化碳抗溶剂法(SAS)辅助制备PHAs空白微球及载药微球的研究现状,探讨了该方法制备载药微球的原理及优势。最后对其研究发展方向进行了展望。     

悬浮聚合法制备稳定的多孔高分子微球

以二乙烯基苯为交联剂,正十八醇为致孔剂,在过氧化苯甲酰引发下悬浮聚合苯乙烯、丙烯腈,制备苯乙烯-二乙烯基苯-丙烯腈交联高分子微球.用SEM(扫描电子显微镜)分析微粒平均粒径及形貌,红外光谱分析高分子微球的结构,原位生成磁性四氧化三铁并用磁天平表征磁响应性的变化,结果表明聚合物为粒径在0.5～7 μm的稳定、多孔高分子微球.     

1聚合物微球的合成与应用

简要介绍了高分子微球的相关制备技术及优缺点，重点介绍了聚合物微球在医学、生物、电子、化工等相关领域的特殊功能应用研究进展。     

响应性壳聚糖微球的研究

随着绿色经济的发展, 生物可降解的天然高分子引起了人们的兴趣, 壳聚糖作为一种天然高分子材料, 具有良好的生物相容性、生物可降解性、抗菌性、保湿性、成膜性等.近年来, 利用壳聚糖微球作为载体并将其应用于药物的可控释放以及吸附等方面的研究受到了越来越多科学研究者的关注, 尤其是在赋予壳聚糖响应性、实现其功能化等方面.综述...     

单分散聚合物微球的合成技术

综述了单分散聚合物微球的制备方法和研究新进展,具体介绍了分散聚合法、种子聚合法,同时对一些特殊的单分散微球制备方法如SPG玻璃膜乳化法,微波、电离辐射诱导聚合法,气溶胶光聚合法进行了简要介绍,并对这些方法进行评述分析,可知前三种方法对环境污染小,为聚合物微球的工业化绿色生产提供可能.     

Simple fabrication of hollow poly-lactic acid microspheres using uniform microbubbles as templates

A simple method was developed that uses microbubbles as templates to fabricate hollow microspheres covered with a biodegradable polymer. By stably keeping microbubbles with the diameter of about 2 µm inside a solvent droplet dissolving a biodegradable polymer and then slowly drying the solvent, hollow microspheres that had an average inner diameter of about 2 µm and a shell thickness of about 500 nm were obtained. This simple method was successfully used to easily fabricate uniform hollow microspheres covered with poly-lactic acid (PLA) by using uniform 2-µm-diameter bubbles as templates.     

Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair

To repair complexly shaped tissue defects, an injectable cell carrier is desirable to achieve an accurate fit and to minimize surgical intervention. However, the injectable carriers available at present have limitations, and are not used clinically for cartilage regeneration. Here, we report nanofibrous hollow microspheres self-assembled from star-shaped biodegradable polymers as an injectable cell carrier. The nanofibrous hollow microspheres, integrating the extracellular-matrix-mimicking architecture with a highly porous injectable form, were shown to efficiently accommodate cells and enhance cartilage regeneration, compared with control microspheres. The nanofibrous hollow microspheres also supported a significantly larger amount of, and higher-quality, cartilage regeneration than the chondrocytes-alone group in an ectopic implantation model. In a critical-size rabbit osteochondral defect-repair model, the nanofibrous hollow microspheres/chondrocytes group achieved substantially better cartilage repair than the chondrocytes-alone group that simulates the clinically available autologous chondrocyte implantation procedure. These results indicate that the nanofibrous hollow microspheres are an excellent injectable cell carrier for cartilage regeneration.     

可生物降解性聚合物-层状硅酸盐纳米复合材料的研究进展

可生物降解性聚合物一层状硅酸盐纳米复合材料比聚合物基体有更好的力学强度、热稳定性、热变形温度、气体阻隔特性和更快的降解速率，表现出剪切变稀、模量升高、似固体行为等流变特性。文中综述了可生物降解性聚合物纳米复合材料的制备方法、表征手段、性能测试及其应用等方面的研究进展。     

Encapsulation and characterization of controlled release flurbiprofen loaded microspheres using beeswax as an encapsulating agent

The aim of the present study was to extend the use of flurbiprofen in clinical settings by avoiding its harmful gastric effects. For this purpose, we designed the controlled release solid lipid flurbiprofen microspheres (SLFM) by emulsion congealing technique. Drug was entrapped into gastro resistant biodegradable beeswax microspheres which were prepared at different drug/beeswax ratios 1:1, 1:2 and 1:3 using gelatin and tween 20 as emulsifying agents. The effect of emulsifiers and the effect drug/beeswax ratios were studied on hydration rate, encapsulating efficiency, micromeritic properties, scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (X-RD) analysis and in vitro drug release at pH 1.2 for 2 h and at pH 6.8 for 10 h. SEM revealed that microspheres made with tween 20 were smooth while microspheres made with gelatin showed porous morphology, however, they were all spherical in nature. The practical yield (recovery) showed a dependence on drug-beeswax ratio and it was variable from 53 to 84%. High loading encapsulating efficiency of flurbiprofen from 8 to 94% was achieved. FTIR and DSC analysis confirmed the absence of any drug polymer interaction indicating drug stability during microencapsulation. X-RD of pure flurbiprofen shows sharp peaks, which decreases on encapsulation, indicating decrease in the crystallinity of drug in microspheres. The micromeritic studies confirmed the presence of excellent and good flow properties of microspheres. Entrapment efficiency, morphology, practical yield, hydration rate, flow properties demonstrated their dependence on the HLB value of emulsifiers and emulsifiers with higher HLB were found more appropriate for effective microencapsulation of flurbiprofen. The release kinetics followed zero order mechanism of drug release at pH 6.8. Release pattern depends on the morphology of flurbiprofen microspheres and amount of beeswax used in the microspheres preparation. The microspheres prepared with high HLB values i.e., tween 20 showed effective control of drug release from microspheres. The absence of drug release at pH 1.2 proved the suitability of beeswax for its use as a gastro resistant material.     

Preparation and characterisation of calcium-phosphate porous microspheres with a uniform size for biomedical applications

In the present work, a novel route for the preparation of porous ceramic microspheres is described. Two ceramic powders, calcium-titanium-phosphate (CTP) and hydroxyapatite (HAp), were mixed with a sodium alginate solution that enabled the preparation of spherical particles, using the droplet extrusion method combined with ionotropic gelation in the presence of Ca²⁺. The spherical particles were subsequently sintered, to burn-off the polymer and obtain calcium-phosphate microspheres with a uniform size and an interconnected porous network. CTP microspheres with diameters ranging from 513 ± 24 μm to 792 ± 35 μm and with pores of approximately 40 μm were obtained. HAp microspheres presented diameters of 429 ± 46 μm and 632 ± 40 μm and pores of ca. 2 μm. Depending on the formulations tested, the structure of both calcium phosphates may become altered during the sintering process, suggesting that the ratio between the ceramic phase and the polymer solution is a critical parameter. Porous microspheres prepared using the described methodology are promising candidates as bone defect fillers and scaffolds for bone tissue regeneration.     

Controlled release of BSA by microsphere-incorporated PLGA scaffolds under cyclic loading

Localized delivery of bioactive molecules from porous biodegradable scaffolds is very important in advanced tissue engineering strategies, and it is necessary to study the delivery under dynamic loading which mimics the in vivo biomechanical environments. In this study, bovine serum albumin (BSA), a model of bioactive proteins, was incorporated into porous poly(l-lactide-co-glycolide) (PLGA) scaffolds by seeding BSA-loaded microspheres onto the scaffold pore wall, where the microspheres of poly(ethylene glycol)-b-poly(l-lactide) (PELA) were prepared by double emulsion technique. The in vitro release behavior of BSA from the scaffold under dynamic cyclic loading was studied in comparison with that under a static condition as well as from PELA microspheres. It was observed that the microsphere-incorporated scaffold prolonged BSA release with respect to the microspheres. The cyclic loading accelerated the release of BSA from the scaffold and the cumulative release on day 10 reached 85% of the totally encapsulated BSA. The delivery under a dynamic condition would be an initial study of in vivo localized delivery of growth factors.     

Synthesis of aligned porous poly(ε-caprolactone) (PCL)/hydroxyapatite (HA) composite microspheres

We synthesized poly(ε-caprolactone) (PCL)/hydroxyapatite (HA) composite microspheres with an aligned porous structure and evaluated their potential applications in bone tissue engineering. A range of HA particles (0, 5, 10 and 20 wt.% in relation to the PCL polymer) were added to a PCL solution in order to improve the biocompatibility of the porous PCL/HA composite microspheres. All the synthesized microspheres showed that the HA particles were distributed well in the PCL matrix, while preserving their aligned porous structure. The average size of the PCL/HA composite microspheres increased from 62 ± 7 to 179 ± 95 μm with increasing HA content from 0 to 20 wt.%. The incorporation of the HA particles to the PCL polymer led to a considerable improvement in in vitro bioactivity, which was assessed by immersing the PCL/HA composite microspheres in simulated body fluid (SBF). A number of apatite crystals could be precipitated on the surface of the aligned porous PCL/HA composite microspheres after soaking in the SBF for 7 days.     

聚烯丙基氯化铵调控下多孔羟基磷灰石微球的合成及作为药物载体的应用研究

选用聚烯丙基氯化铵(PAH)作为晶体生长调节剂, 在水热条件下成功制备了多孔羟基磷灰石(Hydroxyapatite, HAP)中空微球。详细研究了反应时间和添加剂浓度等因素的影响: 150℃水热反应12 h, 控制PAH 浓度0.3~0.5 g/L, 可合成尺寸均匀、孔径密集的HAP中空微球。微球生长经历早期前驱体微结构、异相成核、相转化等不同阶段, 聚合物在各阶段都起到重要的调节作用。以典型的布洛芬(ibuprofen, IBU)作为模型药物, 研究微球的药物负载和脱附能力。结果显示: 多孔微球具有良好的药物负载和释放能力, 吸附量较好, 可达到413.65 mg/g。且药物具有较好的pH响应释放行为, 可作为pH敏感靶向药物载体应用到生物医学等领域。     

淀粉多孔微球研究进展

作为一种天然的、环境友好的功能材料,淀粉多孔微球在生物医药方面的运用变得越来越广泛。本文在阅读一定量文献的基础上,对近年来淀粉多孔微球的研究进行综述,首先讨论了淀粉多孔微球的制备方法,其次论述了淀粉多孔微球的功能性运用,最后对淀粉多孔微球的未来研究进行了展望。