纳米硅酸镁锂-壳聚糖-海藻酸钠复合支架材料的制备与性能

利用真空冷冻干燥技术, 将不同质量的纳米硅酸镁锂(nLMS)与壳聚糖(CA)和海藻酸钠(SA)混合, 制备了纳米硅酸镁锂-壳聚糖-海藻酸钠(nLMS-CS-SA)复合支架材料. 研究了不同质量分数(1%, 2%, 3%, 4%)的nLMS对nLMS-CS-SA复合支架材料的外形、 微观形貌、 溶胀率、 孔隙率、 体外降解性能和生物相容性的影响, 以确定nLMS-CS-SA复合支架材料中最佳nLMS含量. 研究结果显示, nLMS-CS-SA复合支架材料是具备形态可塑性的多孔状固体, 各组材料纵断面呈片层状, 其结构疏松且内部孔隙具有高度连通性; 随着nLMS含量的增加, nLMS-CS-SA复合支架材料的孔隙率呈现先降后升的趋势; 当nLMS的质量分数为3%时, 其溶胀比最小, 体外降解速率最慢; nLMS的添加降低了nLMS-CS-SA复合支架材料的毒性. 因此, nLMS在nLMS-CS-SA复合支架材料中的最佳含量为3%.     

聚酯多孔支架降解液对骨髓基质干细胞活力和成骨分化的影响

通过室温模压/粒子浸出方法制备得到聚乙交酯丙交酯(PLGA)多孔支架,每个质量50 mg、孔径200～300μm、孔隙率略大于90%的PLGA85/15多孔支架在10 mL磷酸盐缓冲液(PBS)中37℃体外降解24周.降解液每周换一次,不同时间点的降解液被收集、并加入骨髓基质干细胞(MSC)的培养液或者成骨诱导液中,利用胞外乳酸脱氢酶含量检测、细胞死活染色、四唑盐检测、碱性磷酸酶染色和定量检测的方法考察降解液对MSC的活力和成骨分化能力的影响.实验结果表明,PLGA多孔支架材料在PBS中逐渐降解,其质量、尺寸、孔径、孔与孔的连通性、分子量有不同程度的降低;其降解液在本研究的实验条件下未发现对MSC有明显的细胞毒性,对MSC的活力、增殖以及成骨分化均无显著的负面影响.     

聚dl-丙交酯/羟基磷灰石复合材料Ⅲ.体内外降解性能研究

研究了聚dl 丙交酯 /羟基磷灰石复合材料在体内外降解中力学强度、分子量、重量及微观形貌的变化。体内降解是将聚dl 丙交酯 /羟基磷灰石 (40mm× 3mm× 2mm)植入兔子皮下软组织内 ;体外降解是将试样 (40mm× 6mm× 2mm)浸入到pH为 7.4的磷酸盐缓冲溶液 (3 7± 0 .2℃ )中 ,试样定时取出并进行各项性能测试。研究发现聚dl 丙交酯 /羟基磷灰石复合材料在体内外降解中分子量、力学性能首先大幅度下降 ,重量损失滞后 ,体内降解速率稍快于体外 ,但均为简单本体水解 ;羟基磷灰石延缓了复合材料的降解速率。SEM显示聚dl 丙交酯 /羟基磷灰石块状材料内部降解与吸收速率快于表层 ,表现为“双态降解”特征。     

聚乳酸与聚乳酸-羟基乙酸多孔细胞支架的制备及孔隙的表征

应用溶液烧铸致孔剂浸出技术制备了不同致孔剂用量与不同致孔剂颗粒尺寸条件下的一系列聚乳酸及不同组成的聚乳酸－羟基乙酸多孔细胞支架;用一种改进的方法－重量法测定其孔隙率;在聚乳酸－羟基乙酸多孔支架上进行了软骨细胞培养。研究结果表明,随着制备过程中致孔剂用量的增加,多孔支架的孔隙逐渐增加,而与致孔剂的颗粒大小基本无关;致孔剂的颗粒大小只影响多孔支架的孔径;在致孔剂用量及致孔剂颗粒尺寸都相同的情况下,随着共聚物中乙交酯含量的增加,孔隙率逐渐下降;软骨细胞在支架上繁殖情况良好,三周后已开始分泌细胞外基质。     

超临界二氧化碳中聚(丁二酸-丁二醇/乙二醇)酯(PBES)多孔聚合物的制备与表征

在超临界二氧化碳(scCO2)条件下,制备了可生物降解性的聚(丁二酸-丁二醇/乙二醇)酯(PBES)多孔材料,研究了scCO2的压力、温度对多孔材料的结构形貌和结晶度的影响。 结果表明,材料的孔洞分布、结构形态和结晶度与处理样品的压力、温度关系密切;经过scCO2处理后材料的结晶度有所降低。 孔径均匀分布,为50~200 μm,131 ℃处理样品的孔隙率为55.63%。     

壳聚糖多孔支架电化学辅助沉积羟基磷灰石涂层研究

采用电化学辅助技术控制阴、阳两极溶液中的钙、磷离子定向迁移,进入壳聚糖多孔支架内部发生反应并在孔隙表面沉积,制备了有机-无机复合多孔支架.应用XRD、SEM、煅烧法、孔隙率测定和压缩实验对支架的组成、形貌、无机物沉积量、孔隙率以及压缩强度进行了表征.研究表明,处理后支架孔隙表面沉积了低结晶度的羟基磷灰石,低倍下沉积层均匀致密,在高的放大倍数下发现,沉积层中存在大量的微孔,沉积层表面存在着球状物,该球状物是由许多小片组成的.沉积6 h时沉积量为支架质量的2.81%,支架孔隙率由96.0%减少到89.8%.与纯壳聚糖支架相比,复合支架的压缩强度由0.0550 MPa提高到0.0998 MPa.     

聚对二氧杂环己酮─乙交酯无规共聚物缝合线热处理及体外降解性能研究

本文研究了热处理对聚对二氧杂环己酮-乙交酯无规共聚物合成缝合线力学性能和体外降解性能影响。结果表明：60～80℃温度范围内定长热定型对缝线原有力学性能影响较小；体外降解性能表明，随着热定型温度提高，缝线强度下降速率减缓。DSC测试结果表明，热定型后缝线样品结晶度提高，体外降解过程样品结晶度也逐渐提高，其中，无热定型样品提高幅度最大，说明热定型可使缝线样品聚集态结构紧密，水解速度减慢。     

与胶原特异性结合的BMP2模拟肽/PLGA 3D打印复合支架的制备及成骨诱导活性

将胶原绑定结构域(CBD)多肽序列与骨形态发生蛋白2模拟肽(BMP2-MP)序列连接制备具有胶原绑定能力的CBD-BMP2-MP, 再将CBD-BMP2-MP与聚丙交酯-乙交酯/胶原(PLGA/COL)3D打印支架相结合, 以支架表面的胶原成分为媒介, 将CBD-BMP2-MP更有效地固定于骨修复材料上, 达到对其进行改性的目的. 利用扫描电子显微镜(SEM)、 电子万能试验机和接触角测量仪对复合支架表面形貌、 力学强度和亲水性等材料学性能进行评价. 用荧光成像法评测 CBD-BMP2-MP及BMP2-MP与支架材料的结合能力. 在各组支架材料表面接种MC3T3-E1细胞进行体外培养, 采用CCK-8、 鬼笔环肽荧光染色、 茜素红染色及qPCR综合评价细胞在材料表面的黏附、 增殖和成骨分化等细胞行为, 研究CBD-BMP2-MP修饰的3D多孔PLGA/COL复合支架的生物学性能. 研究结果表明, 利用3D打印技术制备的多孔支架具有形貌可控的孔隙结构, 为细胞生长创造更有利的细胞微环境, 支架表面胶原成分的加入提高了支架材料的亲水性, 同时对支架材料本身的力学性能无任何影响, 提高了复合支架本身的生物相容性. 与普通BMP2-MP相比, CBD-BMP2-MP具有更好的胶原绑定能力, 与复合支架的结合更稳定, 提高了PLGA/COL复合支架对BMP2-MP的负载能力. 支架表面负载CBD-BMP2-MP后具有极强的促细胞成骨分化能力. MC3T3-E1细胞表现出更高的钙沉积能力, 并且成骨分化相关基因Runx2, ALP, COL-I及OPN等水平也有了明显提升. 表明CBD-BMP2-MP多孔复合支架具有良好的生物相容性和成骨诱导活性, 在骨组织修复领域具有良好的应用前景.     

乙酰化淀粉/DL-丙交酯接枝共聚物的合成及降解性能研究

用醋酸乙烯酯和玉米淀粉反应制备出了不同取代度乙酰化淀粉，再用乙酰化淀粉同DL－丙交酯接枝共聚合成乙酰化淀粉／DL－丙交酯接枝共聚物。研究了原料配比，淀粉取代度对接枝反应单体转化率（C％），接枝率（G％）接枝效率（GE％）和接枝支链数均分子量（Mn)的影响，结果表明在给定的试验条件下接枝共聚反应的C％，G％，GE％和Mn可分别达到40％，225％，80％和1．4万。接枝共聚物在磷酸缓冲溶液和户外土壤掩埋降解实验表明，在160天内样品失重率分别为71％和60％，表明合成的乙酰化淀粉／DL－丙交酯接枝共聚物具有很好的降解性能。     

氧化石墨烯-海藻酸钠-壳聚糖复合支架的制备及表征

通过冷冻干燥技术, 将不同量的氧化石墨烯与海藻酸钠和壳聚糖复合, 构建复合支架材料. 研究了不同的氧化石墨烯含量(质量分数0, 0.3%, 0.5%, 0.7%, 1%)对支架材料微观结构、 孔隙率、 溶胀比、 体外降解性能、 机械性能及生物相容性的影响, 以确定复合支架中最佳氧化石墨烯含量. 研究结果表明, 复合材料呈固态海绵状结构, 具有一定的形态可塑性; 扫描电子显微镜观察发现, 各组支架均为三维网状结构, 随着氧化石墨烯含量的增加, 孔隙尺寸逐渐降低, 孔壁厚度增加, 孔隙尺寸在140~240 μm之间; 随氧化石墨烯含量的增加, 复合支架溶胀比和体外降解速率逐渐降低, 而机械强度明显增强; 体外细胞毒性显示, 当氧化石墨烯质量分数为0.3%时, 细胞存活率最高, 而当氧化石墨烯含量增高时, 细胞活性会被明显抑制, 造成细胞死亡. 因此, 氧化石墨烯在复合支架中最佳含量为0.3%.     

Fabrication of poly(lactide‐co‐glycolide) scaffold embedded spatially with hydroxyapatite particles on pore walls for bone tissue engineering

Poly(lactide‐co‐glycolide) (PLGA) scaffolds embedded spatially with hydroxyapatite (HA) particles on the pore walls (PLGA/HA‐S) were fabricated by using HA‐coated paraffin spheres as porogens, which were prepared by Pickering emulsion. For comparisons, PLGA scaffolds loaded with same amount of HA particles (2%) in the matrix (PLGA/HA‐M) and pure PLGA scaffolds were prepared by using pure paraffin spheres as porogens. Although the three types of scaffolds had same pore size (450–600 µm) and similar porosity (90%–93%), the PLGA/HA‐S showed the highest compression modulus. The embedment of the HA particles on the pore walls endow the PLGA/HA‐S scaffold with a stronger ability of protein adsorption and mineralization as well as a larger mechanical strength against compression. In vitro culture of rat bone marrow stem cells revealed that cell morphology and proliferation ability were similar on all the scaffolds. However, the alkaline phosphatase activity was significantly improved for the cells cultured on the PLGA/HA‐S scaffolds. Therefore, the method for fabricating scaffolds with spatially embedded nanoparticles provides a new way to obtain the bioactive scaffolds for tissue engineering. Copyright © 2011 John Wiley & Sons, Ltd.     

Preparation and mechanical behavior of PLGA/nano-BCP composite scaffolds during in-vitro degradation for bone tissue engineering

In this paper, the yield strength and elastic modulus of Poly (lactide-co-glycolide) (PLGA) and PLGA/nano-biphasic calcium phosphate (nBCP) composite scaffolds, before and during in-vitro degradation, have been evaluated. Composite scaffolds were made by using PLGA matrix and 10-50 wt.% nBCP powder as the reinforcement material. All scaffolds, with more than 89% porosity, were fabricated by thermally-induced phase separation (TIPS). During in-vitro degradation (0-8 weeks), the PLGA/nBCP scaffolds showed both more weight loss and better mechanical properties as compared to neat PLGA scaffolds. The PLGA/nBCP scaffolds with 30 wt.% nBCP illustrated the highest value of yield strength among the composite scaffolds, before and after degradation, until 6 weeks. After 8 weeks, the yield strength values were very poor and close to each other. The values of elastic modulus for all samples were less than the half of their initial values after 6 weeks. However, after 8 weeks, the elastic moduli of all samples reduced to negligible values.     

Nano‐hydroxyapatite/polyamide66 composite tissue‐engineering scaffolds with anisotropy in morphology and mechanical behaviors

Based on a biomimetic conception, nano‐hydroxyapatite (n‐HA)/polyamide66 (PA66) composite scaffolds were prepared with anisotropic properties both in morphology and mechanical behavior. A novel improved thermally induced phase separation (TIPS) technique was developed to generate orientation‐structured scaffolds for tissue engineering. The physiochemical, morphological, and mechanical properties of the resultant scaffolds were evaluated. According to the results, the improved TIPS method exhibited good processability and reproducibility and enabled the composite scaffolds to have a high content of inorganic fillers. The morphological study proved that the n‐HA/PA66 scaffolds exhibited unidirectional microtubular architecture with high porosity (ca. 80–85%) and an optimal pore size ranging from 200 to 500 μm. Besides, the effect of n‐HA content on the morphology of the scaffolds was studied, and the results indicated that the obtained scaffolds presented an improvement in anisotropic morphology with increase of n‐HA content. The anisotropy was also evaluated in the mechanical properties of the scaffolds, that is, the longitudinal compressive strength and modulus were ～1.5 times of the transverse ones. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 658–669, 2009     

Solvent-assisted room-temperature compression molding approach to fabricate porous scaffolds for tissue engineering

This study investigated the room-temperature compression molding/particle leaching approach to fabricate three-dimensional porous scaffolds for tissue engineering. Scaffolds with anatomical shapes (ear, joint, tube, cylinder) were made from biodegradable poly(D,L-lactide) and poly[(D,L-lactide)-co-glycolide]. The utility of this room-temperature compression approach comes from the effect of solvent assistance, but the tendency for post-molding scaffold shrinkage is a problem unique to this method and is thus examined with emphasis in this paper. Scaffold shrinkage was found to be tolerable under normal fabrication conditions with high salt contents, which is just what the preparation of highly porous scaffolds requires. Furthermore, the resultant porosities after salt leaching were measured as well as the initial scaffold shrinkages after solvent evaporation, and the relation between them was revealed by theoretical analysis and confirmed by comparison with experimental measurements. The pores were interconnected, and porosity can exceed 90%. The effects of porosity on the mechanical properties of porous scaffolds were also investigated. This convenient fabrication approach is a prospective method for the tailoring of porous scaffolds for a variety of possible applications in tissue engineering and tissue reconstruction.     

A comparative study of the in vitro degradation of poly(l-lactic acid)/β-tricalcium phosphate scaffold in static and dynamic simulated body fluid

Porous poly(l-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) composite is a new promising scaffold for bone tissue engineering. Porous scaffolds fabricated by liquid anti-solvent precipitation principle were subjected to degradation in dynamic simulated body fluid (DSBF) and in static simulated body fluid (SSBF) at 37 °C for 24 weeks, respectively. Results indicated that a large number of apatite layer were formed on the scaffolds. The results further indicated that SBF flow decreased the degradation rate of molecular weight and compressive strength significantly. The porosity and mass changes were related to the apatite formation and SBF flow. All the results might be owed to the mutual effects of the flow of SBF and the addition of β-TCP. The degradation rate of scaffolds could be adjusted by the additional fraction of β-TCP to meet the requirements of application in vivo.     

Porous scaffolds based on cross-linking of poly(L-glutamic acid)

Porous scaffolds based on water-soluble PLGA and CS were prepared. The pores were verified to be alveolate, uniform and continuous. The effects of freezing temperature, freeze-drying time, solid content and molecular weight of reactants on the pore structure of the scaffolds were studied. The scaffold morphology could be adjusted by changing the freezing temperature and solid content of reacting polymer. Their degradation rate can be adjusted by changing the proportion of PLGA and CS. The porosity of scaffolds was higher than 90% and the high swelling ratio showed that these scaffolds had excellent hydrophilic performance. The in vitro culture of chondrocytes indicates that the obtained PLGA/CS porous scaffolds are very promising biomaterials for tissue engineering applications.     

The electrospun poly(ε‐caprolactone)/fluoridated hydroxyapatite nanocomposite for bone tissue engineering

Biodegradable cell‐incorporated scaffolds can guide the regeneration process of bone defects such as physiological resorption, tooth loss, and trauma which medically, socially, and economically hurt patients. Here, 0, 5, 10, and 15 wt% fluoridated hydroxyapatite (FHA) nanoparticles containing 25 wt% F^? and 75 wt% OH^? were incorporated into poly(ε‐caprolactone) (PCL) matrix to produce PCL/FHA nanocomposite scaffolds using electrospinning method. Then, scanning electron microscopy (SEM), X‐ray diffraction (XRD) pattern, and Fourier transform infrared spectroscopy (FTIR) were used to evaluate the morphology, phase structure, and functional groups of prepared electrospun scaffolds, respectively. Furthermore, the tensile strength and elastic modulus of electrospun scaffolds were investigated using the tensile test. Moreover, the biodegradation behavior of electrospun PCL/FHA scaffolds was studied by the evaluation of weight loss of mats and the alternation of pH in phosphate buffer saline (PBS) up to 30 days of incubation. Then, the biocompatibility of prepared mats was investigated by culturing MG‐63 osteoblast cell line and performing MTT assay. In addition, the adhesion of osteoblast cells on prepared electrospun scaffolds was studied using their SEM images. Results revealed that the fiber diameter of prepared electrospun PCL/FHA scaffolds alters between 700 and 900 nm. The mechanical assay illustrated the mat with 10 wt% FHA nanoparticles revealed the highest tensile strength and elastic modulus. The weight loss alternation of mats determined around 1% to 8% after 30 days of incubation. The biocompatibility and cell adhesion of mats improved by increasing the amounts of FHA nanoparticles.     

Fabrication and Properties of Porous Collagen/Hyaluronic Composite Scaffolds Containing Nano-Bioactive Glass for Tissue Engineering

In this work, nano-structured scaffolds were designed for tissue engineering using collagen, hyaluronic acid (HA) and nano-bioactive glass (NBAG) as their main components. The scaffold was prepared via freeze-drying method and the properties including morphology, porosity, compressive strength, swelling ratio and cytotoxicity in-vitro, were also evaluated. The composite scaffolds showed well interconnected macropores with the pore size of ranging from 100 to 500 μm. The porosity percent and swelling ability were decreased with the introduction of NBAG into the collagen/HA hydrogel; however, the compressive strength was enhanced. The cytotoxicity in-vitro study shows that the collagen-HA/NBAG scaffolds have good biocompatibility with improving effect on fibroblastic cells growth. It could be concluded that this scaffold fulfills the main requirements to be considered as a bone substitute.     

Monte Carlo Simulation of Degradation of Porous Poly(lactide) Scaffolds, 1

Summary: Monte Carlo method was used to simulate the degradation of porous PLA scaffolds. The simulated volume was assumed to be divided homogeneously between the pore and solid PLA with the ratio equal to the bulk porosity of the scaffold. The volume was divided into surface and bulk elements where the surface elements were in direct contact with the aqueous degradation medium, while the bulk elements were surrounded by the pore and solid PLA. The effect of degradation time on PLA ester groups and carboxylic acid end‐groups for surface and bulk elements, pH, PLA degradation rate and mass loss, and PLA molecular weight distribution was simulated. For surface elements, pH remained constant at 7.4 over the entire time of degradation, while for bulk elements its value decreased significantly to as low as 5.8. The highest drop in pH within the scaffold was observed for the highest porosity of 90%. There was a lag time of at least 7 weeks in the mass loss for surface as well as bulk elements for porosities ranging from 70 to 90%. The mass loss for bulk elements was considerably faster than the surface elements. This difference in the rate of mass loss between the surface and bulk elements could affect the 3D morphology and dimensional stability of the scaffold in vivo as degradation proceeds. The simulation predicts that, due to differences in the rate of bulk and surface degradation, hollow structures could form inside the scaffold after 19, 17, and 15 weeks for initial porosities of 70, 80, and 90%, respectively.

A schematic diagram illustrating the degradation of an element on the outer surface of the scaffold (surface element) versus an element within the volume of the scaffold (bulk element).     

Fabrication and characterization of chitosan-gelatin/single-walled carbon nanotubes electrospun composite scaffolds for cartilage tissue engineering applications

Cartilage is a connective tissue with a slow healing rate due to lack in blood circulation and slow metabolism. Designing tissue engineering scaffolds modified based on its specific features can assist its natural regeneration process. In this study, the chitosan-gelatin/single-walled carbon nanotubes functionalized by COOH (SWNTs-COOH) nanocomposite scaffolds were fabricated through electrospinning. The effect of each component and different duration of cross-linking were assessed in terms of morphology, porosity, chemical structure, thermal behavior, mechanical properties, wettability, biodegradability, and in vitro cell culture study. Adding SWNTs-COOH decreased fiber diameter, water contact angle and degradation rate while increased tensile strength, hydrophilicity, stability and cell viability, due to their high intrinsic electrical conductivity, and mechanical properties and the presence of COOH functional groups in its structure. All the sample presented a porosity percentage of more than 80%, which is essential for tissue engineering scaffolds. The presence SWNTs-COOH did not have any adverse effect on cytocompatibility. The optimal cross-linking time increased the stability of the scaffolds in PBS. It can be concluded that the chitosan-gelatin/1wt% SWNTs-COOH scaffold can be appropriate for cartilage tissue engineering applications.