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。     

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。     

可降解明胶支架与PLGA支架的性能比较

利用固液相分离与冷冻干燥技术分别制备明胶与PLGA组织工程支架。两种支架微观呈互相连通的多孔结构,孔隙率相似。PLGA支架的压缩模量达到3.22MPa,约为明胶支架的500倍。明胶支架在8周内完全降解,而PLGA支架在8周的降解时间内,质量损失在5%以下。     

丹参素-丝裂霉素C挛药的制备及体外释放研究

为了降低高毒性药物丝裂霉素C(MMC)在沺疗翼状胬肉时的副作用,多靶点联合抑制翼状胬肉成纤维细胞,将其与具备抗成纤维细胞活性及血管保护作用的无毒药物丹参素(DSS)化学偶联为挛药MMC-DSS。体外释放研究表明,MMC-DSS可以积聚在眼表后逐渐释放MMC与丹参素以产生活性。从而获得了一种在翼状胬肉沺疗中结膜血管副作用更低,且能够多靶点产生药效的全新挛药。     

氨苄西林磁性明胶药物微球的制备及控制释放

将药物封装入一个输送系统,以便在适当时间内持续控制药物释放.为此,利用明胶的生物相容性,选用难溶性氨苄西林(AMP)为药物模型,Fe3O4作为磁性内核,戊二醛作交联固化剂,液体石蜡为有机分散介质,采用反相悬液冷冻凝聚法(RPSCC)制备出了磁性AMP明胶核壳微球.用SEM、FT-IR和UV/Vis光谱等考察了药物微球的结构和外观形貌,以及药物在包封后的性质.结果表明磁性明胶药物微球的粒径小于20 μm.氨苄西林微球载药率(w/w)为7.1%,Fe3O4的含量为22.1%,微球包裹率为65.13%.7h内释放的药物占总含药量的72.3%.微球的缓释性能良好.     

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。     

冷冻干燥法制备羟基磷灰石多孔支架

采用冷冻干燥法制备出多孔羟基磷灰石(hydroxyapatite,HA)支架,观察了支架的微观形貌,研究了HA浆料固含量和孔隙率、冷冻速率和孔径尺寸的关系.结果表明:通过调整工艺参数可以使制备出的多孔支架的孔隙率和平均孔径尺寸分别在45%~85%、100~800μm之间变化,孔的连通性较好.支架孔隙率随着浆料固含量的降低而升高,孔隙率最高可达到85%.孔径尺寸随着冷冻速率的升高而减小,减小的速度不断降低.当冷冻速率在1.3~3℃/min之间变化时,孔径尺寸约为800~300μm;当冷冻速率分别为9℃/min和11℃/min时,得到支架的孔径尺寸却相差不大,在90～110μm之间.     

海藻酸钠荧光多孔支架的制备

采用乳化剂交联法,以海藻酸钠(SA)为原料,Ca Cl2为物理交联剂,制备了海藻酸钠多孔支架;然后分别以0.2 mol/L Zn(Ac)2、Zn Cl2和Zn(NO3)2为交联剂,在海藻酸钠溶液质量浓度为15 g/L,温度为8℃的条件下,制备了竖直贯通的多孔支架;冷冻干燥后,将支架浸泡在KOH/甲醇/无水乙醇混合溶液中(Zn O量子点原位合成法),制备了荧光竖直定向多孔支架。研究了海藻酸钠的质量浓度(5 g/L、10 g/L、15 g/L)及不同干燥方法(冷冻干燥和乙醇逐级脱水法)对制备海藻酸钠多孔支架的影响;将成纤维细胞与海藻酸钠多孔支架共培养,考察海藻酸钠多孔支架的生物相容性,采用Cy3(Cy–N–羟基琥珀酰亚胺酯)与DAPI(4,6–二脒基–2–苯基吲哚)双荧光染色法观察细胞生长情况及采用MTT(3–(4,5–二甲基噻唑–2)–2,5–二苯基四氢唑溴盐)法定量检测了海藻酸钠多孔支架的细胞毒性;对荧光多孔支架的形貌和荧光性能进行了表征。     

组织工程多孔支架制备技术进展

综述了天然或合成生物降解材料为原料的组织工程多孔支架的几种制备方法，包括无纺织物／纤维粘结法、溶液浇铸／粒子洗出法、相分离／冻干法、气体成孔法和三维“印刷”等方法。特别评述了近期组织工程多孔支架研究进展及其在骨、软骨和皮肤等组织修复中的应用。     

New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC–SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC–PLA particles prepared by classical method were used as comparison. The formulated MMC–SPC–PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA–MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA–MMC–SPC nanoparticles, and 74.1% for PLA–MMC particles. The IR analysis of MMC–SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method.     

碳包铁对丝裂霉素C的吸附与缓释性能研究

纳米碳包铁粒子是在金属外面包了一层碳的粒子,可直接用于药物包埋.用碳包铁对丝裂霉素溶液进行吸附,研究了其吸附动力学,并测定了药物微球不同温度下的缓释性能.结果表明:碳包铁的吸附性能受反应条件的影响较大,温度和载药量对释放率有一定的影响.     

Development of a Novel Polygalacturonic Acid-Gelatin Blend Scaffold Fabrication and Biocompatibility Studies for Tissue-Engineering Applications

In this study, we report the enhanced osteoblast differentiation of mouse embryonic stem cell (mESC) on a novel polygalacturonic acid (PGA)/gelatin scaffold. The matrices of various PGA/geletin ratios were fabricated, biophysically characterized, and optimized for cell culture applications. Blended 2% PGA/gelatin scaffolds were highly porous and were robust with enhanced mechanical strength. Swelling studies showed they had high swelling capacity (six-fold higher than only gelatin scaffold) along with complete degradation in the presence of phosphate-buffered saline. Cytocompatibility of the matrices was evaluated using mouse fibroblast 3T3-L1 cell line showing normal spreading and proliferation as assessed by scanning electron microscopy (SEM) and MTT assay. Among different blends of PGA/gelatin, 2% PGA/gelatin (2PG) scaffold showed the optimum physical and biological compatibility for use in cell culture and differentiation of mESC, especially for osteoblast differentiation. The scaffold, as reported in this study, presents a promising tool for tissue engineering applications.     

Enhancement of Solute Release From Chitosan Scaffold With Embedded Submillimeter Voids

Chitosan scaffold has potential use in the controlled release of drugs, and as 3-D structure for the formation of tissue matrix. This article describes the solute release behavior of chitosan scaffold that bears embedded voids of submillimeter dimensions. Formaldehyde and glyoxal were considered as crosslinkers, and alcohol ethoxylate was used as the surfactant. Nitrogen gas was bubbled in a fluidic arrangement to generate an ensemble of self-aligned bubbles in chitosan, prior to the crosslinking. The crosslinked gel was dried in a vacuum oven, and subsequently, the absorption capacity of the scaffold in PBS buffer was estimated. The type of crosslinker significantly affected the absorption capacity of the scaffold. The dimensions of the voids immediately after the cross-linking of gel, and also after complete drying were obtained using a digital microscope and a scanning electron microscope respectively. Two levels of porosity are evident from these images. The smaller pores were intrinsically provided by the gel matrix. The larger ones were induced by the fluidic arrangement. The porosity of the gel was measured gravimetrically. The uptake of Vitamin B-12 was found significantly higher when formaldehyde was used as crosslinker instead of glyoxal. The release of Vitamin B-12 in PBS buffer on a shaker was studied. For comparison, the experiment was repeated with a scaffold that did not have any embedded void. The enhancements in the release of Vitamin B-12 due to the presence of voids are estimated in this article. The bubbles, placed in more than one layer, enhanced the porosity and the ability to absorb Vitamin B-12 further.     

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.     

5-氟尿嘧啶明胶微球的制备、表征及释药性能

为了获得粒径为50～100μm的5-氟尿嘧啶／明胶微球（5-Fu／GMs）,采用乳化一化学交联法,讨论了5-Fu用量、乳化剂浓度和水／油比等因素对微球平均粒径、载药量及包封率等的影响。结果表明,5-Fu／明胶质量比为0．5,乳化剂浓度为0．5％和水／油相体积比为1／10时,可获得最大的载药量30．1％和包封率90．2％。体外释药性能表明5-氟尿嘧啶明胶微球具有明显的药物缓释作用。