新型三维连通多孔钛的制备及特性*

目的将具有良好生物相容性的钛制成类似松质骨结构,具有较高的强度和良好的生物性能的多孔材料。方法聚氨酯泡沫海棉做成孔径200～600μ,孔隙率50%～70%的三维连通多孔结构,作为钛粉载体。烧结,制成具有三维连通结构的多孔钛,测定生物力学性能。结果制成的多孔钛,具有三维、连通结构,与人股骨头松质骨结构相似。孔径300～600μ,孔隙率50%～60%。三维连通多孔钛的平均弹性模量为0．6～0．7GPa。结论①本实验三维连通多孔钛,达到了理想的孔径和孔隙率,弹性模量适中,可以广泛应用在骨科各个领域。②三维连通多孔钛还存在着连通孔的闭塞率较高,整体强度不均匀问题。     

多孔聚乙烯醇/明胶软骨组织工程支架复合材料的制备及其生物相容性

背景：以明胶为基体制备的组织工程支架材料具有良好的生物相容性和生物降解性能,但存在力学性能低,降解速率难以控制的缺陷。 目的：制备一种软骨组织工程支架材料多孔聚乙烯醇/明胶复合物,并检测其理化性能和生物相容性。 方法：采用乳化发泡法制备聚乙烯醇/明胶多孔支架,并通过电镜分析、力学测试、皮下植入实验,检测材料孔径和孔隙率、IR光谱、力学性能和生物相容性。 结果与结论：多孔材料内部呈三维网状多孔结构,孔径均匀,有相似的孔隙率61.8%,含水率44.6%,抗拉强度为(5.01±0.03) MPa,抗压强度为(1.47±0.36) MPa,有较好的力学性能,IR光谱分析表明材料内部结构均匀。皮下植入后,炎症反应逐渐减轻,囊壁逐渐变薄,并趋于稳定,提示多孔聚乙烯醇/明胶支架材料具有较好的生物相容性和力学性能。     

医用负压封闭引流聚氨酯泡沫材料的制备及性能研究

目的通过聚氨酯发泡制备出能应用于负压封闭引流技术的聚氨酯敷料。方法通过正交实验设计聚氨酯泡沫一步法发泡工艺,并对制备的聚氨酯泡沫进行物理机械性能测试和表面形态观察,从中选取出一组综合性能最佳的聚氨酯泡沫配方,并对其进行优化设计。对优化配方制备的聚氨酯泡沫进行细胞毒性和溶血实验生物学评价。结果制备的聚氨酯泡沫的表观密度为20~35 kg/m3,拉伸强度为16~21 N。细胞体外毒性测试所得细胞相对增殖率为90.1%,符合国家细胞毒性安全标准。聚氨酯泡沫溶血率为2.53%,低于5%的国家标准。一步法发泡所制备的聚氨酯泡沫具有良好的物理机械性能和生物相容性。结论聚氨酯泡沫作为医用负压引流材料具有良好的应用前景,但还需对负压引流效果及其他生物相容性进行进一步的测试。     

透明质酸改性的聚乳酸支架

背景：聚乳酸材料不具备细胞外基质材料的良好细胞亲和性能,采用化学方法将透明质酸交联制得的水凝胶具有良好的生物相容性。 目的：以透明质酸对新型多孔隙率聚乳酸支架的进行改性,观察改性后支架的细胞相容性的改变。 方法：采用盐析法制备出高孔隙率聚乳酸支架,采用低浓度NaOH进行表面轻度水解后,利用EDC和透明质酸进行支架的改性。 结果与结论：透明质酸改性聚乳酸支架在扫描电镜下显示为多微孔的三维立体结构,孔壁及界面平滑,孔隙之间可见更细小微孔相连。改性聚乳酸支架水滴渗入较快,改性后多孔支架的保水能力与吸水能力得到明显的改善;透明质酸改性聚乳酸支架上细胞黏附及增殖优于未改性聚乳酸支架。透明质酸改性聚乳酸组软骨细胞生长密度及基质分泌更加旺盛。表明透明质酸改性聚乳酸多孔支架仍保持多孔的三维结构,其水亲和力、吸水能力、保水能力和细胞相容性均得到明显改善。 关键词：透明质酸;聚乳酸;多孔支架;表面改性;水亲和力;吸水能力 doi:10.3969/j.issn.1673-8225.2012.03.023     

壳聚糖/介孔生物活性玻璃多孔膜的制备和表征

背景：壳聚糖和介孔生物玻璃都具有良好的生物相容性和止血性能,但壳聚糖止血作用有限,介孔生物玻璃粉体方式止血,给应用带来不便。 目的：制备壳聚糖/介孔生物玻璃复合多孔膜并检测材料的性能。 方法：采用冷冻干燥法制备壳聚糖/介孔生物玻璃复合多孔膜。 结果与结论：通过冷冻干燥法可以实现壳聚糖和介孔生物玻璃的均匀复合。制备的复合多孔膜的孔隙分布较均匀;多孔膜具有很好的吸水性,吸水率的大小与壳聚糖和介孔生物玻璃质量比相关;多孔膜的孔隙率高。     

两种交联剂制备软骨细胞移植支架的比较

目的：试用两种交联剂对小牛真皮基质来源的支架材料进行交联,比较支架的细胞毒性、结构、生物相容性和细胞贴附的差异,为在体动物试验提供实验依据。方法将脱细胞真皮基质分为两组,分别浸入0.05%戊二醛溶液和0.2%水溶性交联剂进行交联,MTT 法检测细胞毒性和溶血率。将交联后的支架分别植入大鼠皮下,评价生物相容性。以排液法粗测孔隙率,并在电镜下观察支架的结构和孔隙大小。培养间充质干细胞并贴附于两种方法处理的材料表面,电镜下观察贴附情况。结果以戊二醛溶液和水溶性交联剂两种方法处理的支架细胞毒性检测均合格,溶血率分别为4.61%与2.97%,均符合国家标准。经戊二醛交联的支架生物相容性差,炎症反应始终存在,水溶性交联剂处理的真皮基质组织相容性较好,仅有轻微的炎症反应。水溶性交联剂制备的支架材料孔隙率为84.3%±5.0%,戊二醛制备的支架材料孔隙率为79.7%±10.8%,差异不具有统计学意义（P >0.05）。戊二醛交联的支架细胞贴附差,而水溶性交联剂制备的支架细胞贴附良好。结论应用水溶性交联剂处理的支架细胞毒性和溶血率检测均合格,具有良好的生物相容性、孔隙率和细胞贴附性,该法可以作为后期制备软骨细胞移植支架的交联方法。     

利福平-异烟肼-控释型载药人工骨的实验研究

开发研究一种能承载多药并有控释特性的载药人工骨。利用三维打印技术,制备具有多层同心圆柱体结构的载药人工骨,并将利福平和异烟肼由内到外按特定顺序加载,观察微观结构、孔隙率、体外药物释放特性和体外细胞生物相容性。所制备的载药人工骨呈多孔结构,孔隙率(61.76±2.53)%、微孔孔径50~100μm,体外药物呈现序贯释放,双药释放峰值依次交替出现,持续释放时间超过50 d,MTT检测示细胞毒性0级,电镜观察细胞生长分化良好,并有大量细胞黏附于载药人工骨表面;三维打印技术可以精确地制备具有复杂结构的载药人工骨,制备的多药控释型载药人工骨具有药物缓释和序贯控释的特性,同时具有良好的孔隙率和细胞相容性,为骨结核治疗提供一种新型有效的手段。     

一种应用于应变场三维细胞培养的组织工程支架

我们从组织工程化组织构建的角度，提出了一种可用于应变场细胞三维培养的组织工程支架。采用表面化学和材料力学方法，探讨了支架的组成、结构、表面特性、力学性质及细胞相容性。利用生物医用聚乙烯醇（PVA）耐水泡沫，表面裱衬生物可降解聚乳酸羟基乙酸共聚物（PLGA）后，具有良好的表面特性和适宜的孔隙率，既能产生一定的弹性回缩，又具有良好的细胞相容性。结果表明，PVA耐水泡沫表面裱衬PLGA为组织工程研究应变对细胞三维培养的影响提供了一种良好的三维支架。     

多孔钽金属的生物学特性:近期临床应用安全但远期反应待证实

背景:多孔钽金属具有整体容积孔隙率高、弹性模量低及表面摩擦系数高等特点,以其稳定的生物学特性、良好的生物相容性和特有的结构性质,引起医学界特别是骨科领域的广泛关注。目的:综述钽金属的生物学特性,包括其机械性能、生物相容性及生物活性。方法:应用计算机检索1990至2014年PubMed数据库、中文科技期刊数据库、万方数据库、维普数据库中有关多孔钽金属的文献。英文检索词为"Porous tantalum,biological character,orthopedic applications",中文检索词为"多孔钽;生物学特性;骨科应用"。结果与结论:多孔钽金属具有较大的孔隙率与表面摩擦力,有与人体骨质接近的弹性模量,有较好的生物相容性,其作为良好的骨科植入材料越来越被大家所接受,目前多应用于一体化髋臼杯、全髋关节翻修臼杯与髋臼增强垫块、多孔钽金属棒及胫骨平台假体、髌骨假体等的制备中。骨外科中应用多种多孔钽金属植入体的短期随访已有报道,临床数据、放射学检查及取出物的组织学分析已证明该材料的实用性和安全性,但该材料的远期效果如何还有待证实。     

一种用于应变场三维细胞培养的组织工程支架

我们从组织工程化组织构建的角度 ,提出了一种可用于应变场细胞三维培养的组织工程支架。采用表面化学和材料力学方法 ,探讨了支架的组成、结构、表面特性、力学性质及细胞相容性。利用生物医用聚乙烯醇(PVA)耐水泡沫 ,表面裱衬生物可降解聚乳酸羟基乙酸共聚物 (PL GA)后 ,具有良好的表面特性和适宜的孔隙率 ,既能产生一定的弹性回缩 ,又具有良好的细胞相容性。结果表明 ,PVA耐水泡沫表面裱衬 PL GA为组织工程研究应变对细胞三维培养的影响提供了一种良好的三维支架。     

用于人体关节植入物的多孔纯钛/钛合金研究

目的研究Ti6Al4V合金基体上经钎焊制得的多孔纯钛／钛合金,并对其各项性能进行表征,探讨其是否适用于人体关节植入物。方法制备钎焊多孔纯钛／钛合金表面多孔层,采用SEM观察其形貌及孔径,采用重量法计算其孔隙率,采用Instron 4057材料试验机进行结合强度测试,并根据国家标准GB／T16886-3完成遗传毒性实验。结果纯钛／钛合金多孔层孔径为100μm以上,孔隙率6％以上;多孔层与基体的结合强度达到27MPa。遗传毒性试验结果为阴性。结论经钎焊可制得纯钛／钛合金球形粉末多孔层,其孔隙率和孔径允许骨细胞长入;多孔层与基体的结合强度能够满足植入要求,并具有较好生物相容性;经钎焊制得的纯钛／钛合金多孔层是一种可用于人体关节植入物的表面结构形式。     

多孔纳米羟基磷灰石/聚酰胺复合骨修复材料的制备

BACKGROUND: Compared with dense bone repair materials, porous materials has lower intensity, but its three-dimensional porous network structure can ensure a larger surface area that is more conducive to cell adhesion, growth and division as well as nutrient transmission. OBJECTIVE: To investigate the preparation and performance of porous nano-hydroxyapatite/polyamide composites. METHODS: Porous nano-hydroxyapatite/polyamide composites were prepared using chemical foaming method, and different composite bone repair materials were made by regulating foaming agent amount and nano-hydroxyapatite content. Mechanical properties, porosity and composition of the composite bone repair materials were detected. RESULTS AND CONCLUSION: Porous nano-hydroxyapatite/polyamide composites were substantially tubular  channels, and had relatively good connectivity and uniform distribution, with a pore size of 260-400 μm, porosity of 35%-57%. Foaming agent amount, nano-hydroxyapatite content and density of composite materials all are influential factors of the total porosity. Porous nano-hydroxyapatite/polyamide composites have better mechanical properties and compressive strength than the cancellous bone, and the foaming agent has no influence on its shape, composition and diffraction peaks.      

Novel porous gelatin scaffolds by overrun/particle leaching process for tissue engineering applications

Porous gelatin scaffolds were prepared using a modified overrun process, which is a novel method for preparing a porous matrix by injecting air and mixing polymer solution at low temperature. The pores in the scaffolds formed by the overrun process exhibited a dual-pore structure due to the injection of air bubbles and ice recrystallization. However, the morphology of the overrun-processed gelatin scaffolds had closed pore structures. The closed pore structure was reformed into a uniformly distributed and interconnected open structure by the combination of the overrun process and a particle-leaching technique (NaCl and sucrose). The mechanical strength and biodegradation rate of gelatin scaffolds were controlled by the matrix porosity and concentration of gelatin solution. Despite higher porosity, overrun processed gelatin scaffolds showed similar mechanical strength to freeze-dried scaffolds. After 1 week of in vitro culturing, the fibroblasts in overrun-processed scaffolds were widely distributed on the surface of the scaffold pores, whereas cells seeded in freeze-dried scaffolds were mainly placed on the top and bottom of the scaffolds. Therefore, the overrun process combined with a particle-leaching technique can be applied to fabricate porous scaffolds with a desirable cellular structure for tissue engineering applications.     

Fabrication of porous ultra-short single-walled carbon nanotube nanocomposite scaffolds for bone tissue engineering

We investigated the fabrication of highly porous scaffolds made of three different materials [poly(propylene fumarate) (PPF) polymer, an ultra-short single-walled carbon nanotube (US-tube) nanocomposite, and a dodecylated US-tube (F-US-tube) nanocomposite] in order to evaluate the effects of material composition and porosity on scaffold pore structure, mechanical properties, and marrow stromal cell culture. All scaffolds were produced by a thermal-crosslinking particulate-leaching technique at specific porogen contents of 75, 80, 85, and 90 vol%. Scanning electron microcopy, microcomputed tomography, and mercury intrusion porosimetry were used to analyze the pore structures of scaffolds. The porogen content was found to dictate the porosity of scaffolds. There was no significant difference in porosity, pore size, and interconnectivity among the different materials for the same porogen fraction. Nearly 100% of the pore volume was interconnected through 20microm or larger connections for all scaffolds. While interconnectivity through larger connections improved with higher porosity, compressive mechanical properties of scaffolds declined at the same time. However, the compressive modulus, offset yield strength, and compressive strength of F-US-tube nanocomposites were higher than or similar to the corresponding properties for the PPF polymer and US-tube nanocomposites for all the porosities examined. As for in vitro osteoconductivity, marrow stromal cells demonstrated equally good cell attachment and proliferation on all scaffolds made of different materials at each porosity. These results indicate that functionalized ultra-short single-walled carbon nanotube nanocomposite scaffolds with tunable porosity and mechanical properties hold great promise for bone tissue engineering applications.     

Processing and biocompatibility evaluation of laser processed porous titanium

The Laser Engineered Net Shaping (LENS™) method was used to fabricate porous Ti implants. Porous Ti structures with controlled porosity in the range of 17–58 vol.% and pore size up to 800 μm were produced by controlling LENS™ parameters, which showed a broad range of mechanical strength of 24–463 MPa and a low Young’s modulus of 2.6–44 GPa. The effects of porous structure on bone cell responses were evaluated in vitro with human osteoblast cells (OPC1). The results showed that cells spread well on the surface of porous Ti and formed strong local adhesion. MTT assay indicated LENS™ processed porous Ti provides a preferential surface for bone cell proliferation. Porous Ti samples also stimulated faster OPC1 cell differentiation compared with polished Ti sheet, which could be due to the change in cell morphology within the pores of Ti samples. More extracellular matrix and a higher level of alkaline phosphatase expression were found on the porous samples than on the Ti sheet. This can be beneficial for faster integration of porous implant with host bone tissue. The results obtained also indicated that a critical pore size of 200 μm or higher is needed for cell ingrowth into the pores, below which OPC1 cells bridged the pore surface without any growth in the pores.     

聚乳酸-羟基乙酸共聚物/硅酸钙三维多孔骨组织工程支架的构建与性能

BACKGROUND: Some disadvantages exsist in commonly used poly(lactic-co-glycolic acid) (PLGA) scaffolds, including acidic degradation products, suboptimal mechanical properties, low pore size, poor porosity and pore connectivity rate and uncontrollable shape. OBJECTIVE: To construct a scaffold with three-dimensional (3D) pores by adding calcium silicate to improve the properties of PLGA, and then detect its degradability, mechanical properties and biocompatibility. METHODS: PLGA/calcium silicate porous composite microspheres were prepared by the emulsion-solvent evaporation method, and PLGA 3D porous scaffold was established by 3D-Bioplotter, and then PLGA/calcium silicate composite porous scaffolds were constructed by combining the microspheres with the scaffold using low temperature fusion technology. The compositions, morphology and degradability of the PLGA/calcium silicate porous composite microspheres and PLGA microspheres, as well as the morphology, pore properties and compression strength of the PLGA 3D scaffolds and PLGA/calcium silicate composite porous scaffolds were measured, respectively. Mouse bone marrow mesenchymal stem cells were respectively cultivated in the extracts of PLGA/calcium silicate porous composite microspheres and PLGA microspheres, and then were respectively seeded onto the PLGA 3D scaffolds and PLGA/calcium silicate composite porous scaffolds. Thereafter, the cell proliferation activity was detected at 1, 3 and 5 days. RESULTS AND CONCLUSION: Regular pores on the PLGA microspheres and internal cavities were formed, and the PH values of the degradation products were improved after adding calcium silicate. The fiber diameter, pore, porosity and average pore size of the composite porous scaffolds were all smaller than those of the PLGA scaffolds. The compression strength and elasticity modulus of the composite porous scaffolds were both higher than those of the PLGA scaffolds (P < 0.05). Bone marrow mesenchymal stem cells grew well in above microsphere extracts and scaffolds. These results indicate that PLGA/calcium silicate composite porous scaffolds exhibit good degradability in vitro, mechanical properties and biocompatibility.     

基于丝素/胶原/羟基磷灰石仿生骨材料的多维结构及其性能

目的 体外构建丝素蛋白（silk fibroin,SF）、I型胶原(type I collagen,Col-I)和羟基磷灰石(hydroxyapatite, HA)共混体系制备二维复合膜和三维仿生支架,研究其理化性质和生物相容性,探讨其在组织工程支架材料中应用的可行性。方法 通过在细胞培养小室底部共混SF/Col-I/HA以及低温3D打印结合真空冷冻干燥法制备二维复合膜及三维支架。通过机械性能测试、电子显微镜和Micro-CT检测材料的理化性质,检测细胞的增殖评估其生物相容性。结果 通过共混和低温3D打印获得稳定的二维复合膜及三维多孔结构支架;力学性能具有较好的一致性,孔径、吸水率、孔隙率和弹性模量均符合构建组织工程骨的要求;支架为网格状的白色立方体,内部孔隙连通性较好; HA均匀分布在复合膜中,细胞黏附在复合膜上,呈扁平状;细胞分布在支架孔壁周围,呈梭形状,生长及增殖良好。结论 利用SF/Col-I/HA共混体系成功制备复合膜及三维支架,具有较好的孔连通性与孔结构,有利于细胞和组织的生长以及营养输送,其理化性能以及生物相容性符合骨组织工程生物材料的要求。     

The precision structural regulation of PLLA porous scaffold and its influence on the proliferation and differentiation of MC3T3-E1 cells

A thermal-induced phase separation combined sugar template method was used to fabricate the Poly (L-lactide) acid (PLLA) scaffolds with precisely regulated porous structure. The effect of tuned porous structure of scaffolds on osteoblasts proliferation and differentiation was investigated. The results showed that the pore diameters (200–300, 300–400, 400–500 μm), porosity and interconnectivity of PLLA scaffolds can be accurately controlled indicated by scanning electron microscope. The results of cell experiments showed that the porous structure including the pore size and interconnectivity of scaffolds dramatically influence the cell proliferation and differentiation. The scaffold with pore diameter of 400–500 μm exhibited the highest cell viability and alkaline phosphatase activity among all the scaffolds for the MC3T3-E1 cells. The higher cell proliferation and biocompatibility observed in the 400–500 μm scaffold indicated the high selectivity for MC3T3-E1cells on the pore size of scaffold in tissue engineering. The precise control of the porous structure of scaffold may better guide the cell–matrix interaction in the future research.     

杆状和片状三周期极小曲面模型孔隙特征与力学性能对比

目的分析对比杆状与片状三周期极小曲面(triply periodic minimal surface,TPMS)模型孔隙特征与力学性能,构建高比表面积、低刚度和高强度的多孔结构。方法构建相同孔隙率的D、G、P 3种单元杆状TPMS与片状TPMS模型,对比模型的孔径、杆径、比表面积等孔隙特征;利用有限元方法分析模型的力学性能;采用增材制造技术制作多孔钛样件,利用显微镜和扫描电镜观测多孔钛孔隙特征,通过压缩试验检测多孔钛力学性能。结果同种单元片状结构的比表面积均显著高于杆状结构,同种单元片状结构的力学性能明显优于杆状结构。其中,D单元片状TPMS模型的优势最显著,比表面积为13.00 mm~(-1),多孔钛样件的弹性模量、屈服强度和抗压强度分别为(5.65±0.08) GPa、(181.03±1.30) MPa和(239.83±0.45) MPa,比杆状多孔钛样件分别提高43.87%、55.08%和67.21%。结论相同单元的片状TPMS模型在保留有多孔结构低刚度的同时,有更大的比表面积,更有利于细胞的黏附生长,其低刚度、更高强度的力学特性能有效降低应力遮挡,提供足够的力学支撑,是一种理想的骨缺损修复替代物孔隙结构模型。