PLGA多孔支架的制备及性能

多孔支架在组织工程领域发挥着重要作用。本研究基于固液相分离原理,结合冷冻干燥的方法制备PLGA多孔支架,并研究其性能。结果表明,不同起始浓度（5%、7%、9%）制备得到的PLGA支架微观形貌相似,呈现相互连通的多孔结构。随着起始浓度的增加,多孔支架的孔隙率降低,力学性能增强。     

明胶多孔支架固定化过氧化氢酶

以明胶多孔支架为载体,戊二醛为交联剂成功地制备了固定化过氧化氢酶,并对其固定化酶的性质进行了研究。固定化过氧化氢酶活力回收率可高达51.1%。与游离酶相比较,虽然催化效率有所降低,但是其固定化酶在65℃保存的稳定性有明显提高。固定化酶可重复使用10次后,活力仍保持在初始活力的60%以上,其具有良好的操作稳定性。     

热致相分离法制备明胶多孔支架及其性能研究

本文对热致相分离法制备明胶多孔支架及其性能进行了系统的研究。采用冷冻致孔真空干燥法制备了明胶基组织工程多孔支架,并对影响其结构与性能的因素(如明胶溶液浓度、交联剂用量、体系pH值等)进行了考察。实验结果表明:真空冷冻干燥法制备的明胶基多孔组织工程支架都具有三维孔洞结构;所制备的支架平均孔径可达100μm。     

京尼平交联明胶多孔支架的制备及降解

采用天然交联剂京尼平,结合相分离技术与冷冻干燥方法,制备不同交联度的明胶多孔支架。结果表明,支架的交联度随着京尼平浓度的增加而升高,最高可以达到65．3％;不同交联度的明胶支架微观呈相互连通的多孔结构,且孔径随交联度的升高而降低;通过调控明胶支架的交联度,可以调控支架的降解时间。     

负载丝裂霉素C的明胶多孔支架制备及释放

采用单乳化溶剂挥发法制备负载MMC的PLGA微球,通过相分离与冷冻干燥,制备含有载药微球的明胶多孔支架。支架的孔隙率达到90.2%,溶胀率为22.7%,压缩模量为52.1kPa。体外释放实验表明,载药微球中,MMC在5周的累计释放量为77.3%;支架中MMC的释放相对较缓,5周累积释放量为65.2%。这种含有载药微球的明胶复合多孔支架具有潜在的抗瘢痕应用前景。     

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.     

明胶基组织工程支架研究进展

近年来发展出的组织工程技术很好地解决了缺损组织器官再生的难题。而组织工程支架材料的选择与支架的制备是组织工程中的关键。明胶因为同时具有很好的生物相容性与溶胶一凝胶转变等性质而广受组织工程技术的青睐。本文主要讨论了明胶基组织工程支架制备过程中应注意的方法,并针对这些方法展开简要介绍了一些明胶基支架制备的研究工作。     

静电纺PLGA管状支架的构建及其生物力学性能

以具有良好生物相容性、生物可降解性的聚丙交乙交酯(PLGA)为原料,以高速旋转的滚轴为收集装置,通过静电纺丝法,制备PLGA管状支架(d=6mm)。研究不同工艺及乙醇处理对PLGA管状支架形貌结构、微细结构和生物力学性能的影响。结果表明:当纺丝液质量分数为7%,滚轴转速为1500r/min时,可制得纤维形貌规整、分布均匀,直径为(1660±218)nm,孔隙率为80.6%的PLGA管状支架;经乙醇处理后,其孔隙率减小,玻璃化温度和热分解温度提高,热稳定性增强;断裂强度、爆破强度及缝合强力均显著提高。     

明胶在组织工程支架材料中的应用

本文对明胶在组织工程支架材料中的应用进行了评述,表明明胶作为种子细胞的载体具有广阔的应用前景。     

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。     

Biodegradable Laminates Based on Gelatin, 2

Compression moulded laminates based on a gelatin or a blended gelatin/starch matrix reinforced by fabrics (linen or silk) were prepared. Three linen or five silk sheets with a powdered matrix between them were compression moulded at 180 °C for several minutes. In addition, cross‐linked laminates were obtained by using methylenedi(p‐phenyl) diisocyanate as a cross‐linking agent expected to obtain an improved integrity between the matrix and the reinforcing elements. In this way a total of ten uncross‐linked and cross‐linked samples differing in the type of the matrix (gelatin or gelatin/starch) and the type of the reinforcing element (linen or silk), both uncross‐linked and cross‐linked, were obtained. All samples were characterized by means of mechanical testing (Young's modulus, tensile strength, elongation at break and impact strength), as reported in Part 1 of this study. In the present Part 2, the same ten samples were artificially weathered, and changes in both the mechanical properties and the specific wear rate with aging time were followed. It was found that the majority of the mechanical parameters generally became worse with aging time; only the Young's modulus and the tensile strength remained on the same order of magnitude for all laminates. The linen reinforced laminates showed much higher values of the deformation at break, the impact strength and the wear resistance in comparison to the silk reinforced laminates. A similar tendency was found for the sliding wear tests against smooth steel counterparts. A reinforcement of gelatin or gelatin/starch with linen was much more effective in improving the laminate wear resistance than a reinforcement with silk. In addition, the abrasion resistance of neat gelatin was found to be much higher than that of the gelatin/starch blend, as evaluated by the Taber index.

Dependence of Young's modulus on aging time for the neat matrix samples (gelatin and gelatin/starch) and the compression moulded laminates reinforced with fabrics.     

水解明胶对明胶流变性能的影响

明胶是一种大分子,因其优越的理化性质而应用于生活的方方面面。但在实际生产应用中,明胶的高粘度和易结冻的性质可能是需要克服的一大困难。本文考察了在明胶中掺入水解明胶后明胶的流变性能的变化情况,期望能通过此种方法解决明胶粘性强易结冻的问题。     

Biodegradable Laminates Based on Gelatin, 1

Compression‐molded gelatin/starch (1:1 w/w) blend shows improved mechanical properties as compared to neat gelatin. Compression molded laminates reinforced by fabrics were prepared from this blend as well as from neat gelatin. The fabric is either linen or silk. Some of the laminates were additionally crosslinked with methylenedi‐p‐phenyl diisocyanate. Thus a total of ten different samples were obtained. They were characterized by means of mechanical testing, namely measuring of Young's modulus, tensile strength, elongation at break, and impact strength. Substantial increases of Young's modulus and tensile strength in comparison to neat gelatin by a factor of 2–3 and 4–5, respectively, were found for both linen‐ and silk‐reinforced, uncrosslinked and crosslinked laminates. The deformation at break increases much more for the linen‐based than for the silk‐based laminates (about 12 vs. 8 times in average) in comparison to both neat gelatin and gelatin/starch matrix. The improvement in the mechanical properties of the laminates is visible most drastically in the impact behavior. The impact strength is low and almost equal for the neat gelatin and the gelatin/starch samples, but increases by a factor of 10 to 30 when the silk‐ and linen‐reinforcement is involved. This improvement can be partly explained by the good matrix‐fabric adhesion due to their similar chemical composition (in the uncrosslinked samples) and also to the chemical links between them (after crosslinking). In addition, all materials prepared are biodegradable, i.e., environmentally friendly since they do not pollute the nature.

Dependence of the impact strength on the nature of the neat matrix and compression molded laminates reinforced with fabrics.     

组织工程多孔支架材料和制备方法

制备组织工程多孔支架的材料有3大类天然材料、生物陶瓷、合成高分子材料。介绍了其中的一些常用物质,并以聚合物材料的应用为主介绍了含聚合物材料的多孔支架的制备方法纤维粘接法、静电纺丝法、相分离法、气体发泡法、溶液浇注-沥滤法、固体自由成型法、颗粒烧结法。     

Cellular Response of Limbal Stem Cells on PHBV/Gelatin Nanofibrous Scaffold for Ocular Epithelial Regeneration

The aim of this study was to develop a blend of nanofibrous poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/gelatin substrate for limbal stem cell (LSC) expansion that can serve as a potential alternative substrate to replace human amniotic membrane. The human Limbus stem cell was used to evaluate the biocompatibility of substrates (nanofibrous scaffold, and human amniotic membrane) based on their phenotypic profile, viability, proliferation, and attachment ability. Biocompatibility results indicated that the all substrates were highly biocompatible, as LSCs could favorably attach and proliferate on the nanofibrous surface. Microscopic figures showed that the human LSCs were firmly anchored to the substrates and were able to retain a normal corneal stem cell phenotype. Microscopic analyses illustrated that cells infiltrated the nanofibers and successfully formed a three-dimensional corneal epithelium, which was viable for two weeks. Immunocytochemistry (ICC) and real time–PCR results revealed no change in the expression profile of LSCs grown on nanofibrous substrate when compared to those grown on human amniotic membrane. In addition, electrospun nanofibrous PHBV substrate provides not only a milieu supporting LSCs expansion, but also serves as a useful alternative carrier for ocular surface tissue engineering and could be used as an alternative substrate to amniotic membrane.     

Suture Fiber Reinforcement of a 3D Printed Gelatin Scaffold for Its Potential Application in Soft Tissue Engineering

Gelatin has excellent biological properties, but its poor physical properties are a major obstacle to its use as a biomaterial ink. These disadvantages not only worsen the printability of gelatin biomaterial ink, but also reduce the dimensional stability of its 3D scaffolds and limit its application in the tissue engineering field. Herein, biodegradable suture fibers were added into a gelatin biomaterial ink to improve the printability, mechanical strength, and dimensional stability of the 3D printed scaffolds. The suture fiber reinforced gelatin 3D scaffolds were fabricated using the thermo-responsive properties of gelatin under optimized 3D printing conditions (−10 °C cryogenic plate, 40–80 kPa pneumatic pressure, and 9 mm/s printing speed), and were crosslinked using EDC/NHS to maintain their 3D structures. Scanning electron microscopy images revealed that the morphologies of the 3D printed scaffolds maintained their 3D structure after crosslinking. The addition of 0.5% (w/v) of suture fibers increased the printing accuracy of the 3D printed scaffolds to 97%. The suture fibers also increased the mechanical strength of the 3D printed scaffolds by up to 6-fold, and the degradation rate could be controlled by the suture fiber content. In in vitro cell studies, DNA assay results showed that human dermal fibroblasts’ proliferation rate of a 3D printed scaffold containing 0.5% suture fiber was 10% higher than that of a 3D printed scaffold without suture fibers after 14 days of culture. Interestingly, the supplement of suture fibers into gelatin biomaterial ink was able to minimize the cell-mediated contraction of the cell cultured 3D scaffolds over the cell culture period. These results show that advanced biomaterial inks can be developed by supplementing biodegradable fibers to improve the poor physical properties of natural polymer-based biomaterial inks.     

可生物降解聚丙交酯乙交酯微粒制备技术的研究进展

总结了聚丙交酯乙交酯(PLGA)的物理化学和生物性能以及各种制备技术及应用,并综述了近年来国内外科学家们对PLGA微粒的制备和应用所作的研究,对PLGA未来发展的进一步研究提出了看法。