骨组织工程支架的不同孔隙率对成形性能的影响分析

生物三维打印成形的支架孔隙率对引导骨组织的再生极其重要。首先对不同孔径大小的骨组织工程支架模型进行有限元分析。再利用易降解、生物相容性良好的聚乙烯醇(PVA)与羟基磷灰石(HA)混合材料制备出不同孔隙率的骨组织工程支架,对其宏观特征、微观结构和力学性能等重要参数进行对比,得出孔隙率约为60%的骨组织工程支架实际平均抗压强度为14.90 MPa,力学性能与生物相容性最佳,为提高成骨效率奠定实验研究基础。     

组织工程骨支架微宏观模拟分析

应用沉积挤出快速成型技术制备组织工程骨支架过程中,复合生物材料之间相互作用的稳定性、喷头装置中复合凝胶的流动状态及制备工艺参数影响组织工程骨支架成型及成型后骨支架力学性能和孔隙结构。针对以上问题,应用分子动力学模拟软件Materials studio中经典力学工具Forcite对羟基磷灰石(HA)/聚乙烯醇(PVA)/丝素蛋白(SF)共混体系进行模拟,分析羟基磷灰石与生物复合凝胶聚乙烯醇/丝素蛋白相互作用后稳定性。结合三者混合材料特性,通过有限元模拟软件FLUENT分析复合生物材料的流动状态,依据流体分析结果,调整制备骨支架工艺参数。模拟结果表明,HA/PVA/SF三者混合材料具有良好粘结性及力学性能;有限元模拟计算出高粘度材料制备过程中流体状态分布。通过实验,结合流体分布状态,调整最佳制备参数,制备的骨支架具有良好的力学性能,混合生物材料成分基本未发生变化,表面微观孔隙能够达到生物因子驻留和营养物质交换的要求。     

不同浓度聚乙烯醇与羊椎骨粉结合的复合骨支架性能分析

人工骨支架材料的研究一直是组织工程的主要内容,将经过高温煅烧及研磨过的羊椎骨粉和无毒,易降解的聚乙烯醇(PVA)作为成型材料,应用三维打印技术,选择综合质量较好的十字网格填充路径,通过自行开发的三维打印成型设备打印出不同材料浓度下的人工骨支架,并将其低温冷冻干燥。对其孔径、孔密度,力学性能及生物相容性等重要参数进行测定,分析与对比,挑选出最佳的材料浓度,并将最佳浓度下打印的支架用于骨髓干细胞复合培养和兔子体内植入实验,验证该支架材料代替骨的可行性,为生物骨组织工程材料的研究提供一定的依据。     

壳聚糖纤维/磷酸钙骨水泥复合材料人工骨的降解性能

提出添加壳聚糖纤维改善自固化磷酸钙骨水泥的降解性能。根据单一材料均匀降解假设和狗股骨远端松质骨区缺损修复试验研究壳聚糖纤维/骨水泥复合材料人工骨的降解性能。理论分析发现添加的纤维使得人工骨降解量与时间呈现非线性的二次函数关系;纤维质量分数的增减是人工骨降解率的关键影响因素。骨缺损修复试验结果显示人工骨残留材料率与时间形成高阶函数关系,且其试验曲线与骨组织工程理想曲线相似。分析认为,壳聚糖纤维降解速度高于骨水泥造成人工骨在缺损修复的过程中出现多孔结构,进而在促进新生骨组织生长的同时改变了该人工骨的降解规律,结合纤维质量分数的控制,有可能使人工骨的降解速率与骨组织生长相匹配。     

骨组织工程用细胞支架生物材料的研究进展

概述了作为骨组织工程细胞支架修复和替换用的高分子生物材料、生物陶瓷材料、陶瓷/聚合物基复合材料和第三代生物活性复合材料的研究进展。指出模拟天然骨形成机制,可以制备出仿生径向梯度分布、生物活性、无机物增强相与可降解材料复合且多孔的细胞支架材料,将是未来骨组织工程用支架材料的发展趋势。     

挤出沉积成型工艺参数优化研究

通过挤出沉积成型试验,对骨组织工程支架的成型工艺参数进行研究,以提高同轴骨支架组织工程的成型质量和力学性能。方法:首先采用田口法和方差分析法对打印参数进行了优选,其次分析了工艺参数对成型质量和力学性能的显著性影响,最后通过优选的工艺参数对实验结果进行了预测和分析。结果:结果显示,挤出沉积成型最优参数组合为喷头内外芯直径0.6 mm/1.5 mm,层高1.5 mm,打印速度30 mm/h,内芯材料配比1∶1.5;对骨支架特性影响的显著性由强到弱依次为层高、打印速度、内芯喷头直径和内芯材料配比。结论:验证实验结果表明,成型质量和力学性能实验值的信噪比与预估信噪比非常接近,说明挤出沉积成型工艺参数的优化对骨组织工程支架的成型质量和力学性能的提高是十分有效的。     

用于人工骨制造的喷射成形技术

近年来,应用组织工程材料的人工骨因能适时降解并诱导成形人骨,而成为最理想的骨组织人工替代方法和治疗手段。介绍采用多喷射成形制造骨组织工程材料的人工骨,指出用此法得到的人工骨的材料种类及微观组织结构均与人骨高度相似,而采用骨水泥,或含有烧结等步骤,将不具有这种相似性;此人工骨具有与人骨的功能梯度上相一致的材料结构、几何结构和生理功能;人骨生长因子（ＢＭＰ）通过特殊处理,使这达到多维复合,并且具有缓释     

基于骨组织微结构模型的仿生支架逆向设计

模拟人体骨组织结构,满足其几何相容性与生物适应性功能约束要求的多孔骨支架微观结构构建为组织工程中的关键问题。提出一种模拟人体骨组织多孔微观结构来构建仿生支架的逆向设计方法。利用Micro-CT扫描人体胫骨的微观结构,发现其孔的形态与椭球接近。为寻找人体骨结构的分布规律,利用椭圆最小二乘法拟合人体骨的Micro-CT图像,结果表明人体胫骨的微孔短径和长径的值分别分布在0.24mm和0.48mm附近。为使设计的多孔骨支架具有良好的生物和力学性能,将所得胫骨孔径参数创建椭球体,并通过UG二次开发技术将大量的椭球体相交形成仿生支架。研究所得的仿生支架采用人体骨结构参数,在生物和力学性能上与骨结构更为接近,对骨组织工程中的骨支架设计有一定的参考价值。     

骨组织工程多孔生物支架设计研究进展

由人口老龄化、严重不愈合骨折等引起的骨缺损,使人们对人工骨替代物的需求急剧增加。支架作为骨缺损的人工骨替代物,在骨组织工程新骨再生中起到至关重要的作用。人体不同组织(硬骨和软骨),甚至是相同组织的不同部位(骨骼的中部和外部)对支架的力学性能、内部微观结构和孔隙率等参数的要求都不尽相同。如何在理想生物材料的基础上,模拟天然骨的性能和结构,设计出具有可控力学性能、结构和渗透率等性能的支架,一直困扰着组织工程研究者。综述了多孔骨支架在设计成型方面近年来国内外代表性的研究工作,重点探究了多孔支架设计方法,阐述了多孔支架在骨组织工程应用中面临的挑战,为深入开展可控多孔支架的研究和应用提供一定的参考。     

增材制造制备骨组织工程支架研究进展

增材制造是通过逐层叠加材料的方式构造实体的先进制造技术,它能够快速、精确地制备具有特定形态和结构的骨组织工程支架以满足不同患者的需求,在生命科学领域受到了极大的关注。然而,不同的增材制造技术具备各自的优缺点,在临床应用上存在局限性。主要介绍了近年来基于增材制造制备组织工程骨架的研究进展,就几种主要的增材制造技术,具体讨论了当前骨组织工程支架的制备水平,并对该领域的未来发展趋势和面临的挑战进行了展望。     

再生骨支架内部结构性能的综合评价

在分析影响再生骨支架内部微观结构性能因素的基础上,构建了支架内部结构性能的综合评价指标体系。根据各项评价指标对支架的生物活性、力学强度、降解速度等性能的影响程度,建立支架内部结构性能的层次分析模型;基于层次分析法(AHP)理论和计算方法,确定各项评价指标在内部结构性能综合评价中的权重值。基于灰色关联度分析的评价理论,构建支架内部结构性能的综合评价模型;计算各项评价指标的灰色关联度值,以此综合评判支架内部结构性能的优劣,保证再生骨支架具有良好的生物活性、较好的力学性能以及均衡的降解速度。     

Controlled degradation pattern of hydroxyapatite/calcium carbonate composite microspheres

Hydroxyapatite (HAP) is widely used in clinic due to its good biocompatibility and osteoconductivity except for its slow degradation speed. In the present study, spherical calcium carbonate (CaCO₃) is fabricated in the presence of silk protein sericin, which is transmuted into HAP microsphere in phosphate solution with the assistance of microwave irradiation. The effect of reaction conditions on the conversion of CaCO₃ is investigated including reaction time, chemical composition of phosphate solution, and microwave power to get a series of HAP/CaCO₃ composites. The degradation property of the composites is evaluated in vitro. Results show the degradation speed of the composite with higher HAP content is slower. The degradation rate of the composite could be changed effectively by modulating the proportion of HAP and CaCO₃. This work provides a feasible method for the preparation of spherical HAP/CaCO₃ composite with controllable degradability. The composite thus obtained may be an ideal material for bone tissue engineering application. Microsc. Res. Tech. 79:518–524, 2016. © 2016 Wiley Periodicals, Inc.     

有限元分析在骨支架设计中的应用

生物可降解骨支架设计一直是组织工程的重点,为满足骨支架植入后的性能要求,生物力学特性是其设计过程中首要考虑的问题之一。通过对不同孔隙率骨支架的分析,提出骨支架有效弹性模量与孔隙率和材料弹性模量之间的关系式,作为骨支架设计中的参考。分析中所用骨支架的孔隙率通过组合可控微单元体进行调整,对大量的骨支架的有限元分析表明:0.5%总体压应变下有效弹性模量与孔隙率和弹性模量之间关系是线性的以及对于不同属性材料,其弹性模量越高,随着孔隙率的增大,其有效弹性模量减小速度越快。     

Structural evaluation of scaffolds prototypes produced by three-dimensional printing

The fabrication of porous scaffolds with complex architectures represents a challenge in tissue engineering. Recent studies have shown that it is possible to construct tissue-engineered bone repair scaffolds with tight pore size distributions and controlled geometries using 3D printing techniques. In this context, this work aims to evaluate the 3D printing process in order to study its potential for scaffold fabrication. Despite the wide use of porous scaffolds, its design, geometry optimization and mechanical assessment, for successful integration in tissue engineering, require further developments and studies to help in its optimal design. In the present work, cubical scaffolds prototypes with different architectures were produced by 3D printing technology. Scaffolds dimensional accuracy, porosity and mechanical stiffness were comprehensive analysed by means of an experimental investigation. The microporosity, inherent to the fabrication process, and the mechanical characterization of the bulk material were also considered. This paper addresses methodologies to overcome some limitations of 3D printing technique to produce scaffolds for tissue engineering and proposes procedures for their suitable mechanical characterization. Results of this work indicate that 3D printing process has great potential for scaffold fabrication.     

Chitosan-based hyaluronan hybrid polymer fibre scaffold for ligament and tendon tissue engineering

To establish medical use of tissue engineering technology for ligament and tendon injuries, a scaffold was developed which has sufficient ability for cell growth, cell differentiation, and mechanical properties. The scaffold made from chitosan and 0.1 per cent hyaluronic acid has adequate biodegradability and biocompatibility. An animal experiment showed that the scaffold has less toxicity and less inflammation induction. Furthermore, in-vivo animal experiments showed that the mechanical properties of the engineered ligament or tendon had the possibility to stabilize the joint. It was shown that newly developed hybrid-polymer fibre scaffold has feasibility for joint tissue engineering.     

Bioactive composites for bone tissue engineering

One of the major challenges for bone tissue engineering is the production of a suitable scaffold material. In this review the currently available composite material options are considered and the methods of production and assessing the scaffolds are also discussed. The production routes range from the use of porogens to produce the porosity through to controlled deposition methods. The testing regimes include mechanical testing of the produced materials through to in vivo testing of the scaffolds. While the ideal scaffold material has not yet been produced, progress is being made.     

基于快速原型的组织工程支架成形技术

组织工程是生物制造的重要发展阶段,通过先成形生物材料的支架,然后在上面复合细胞的方式,来实现组织器官的人工制造。支架的性能在组织工程的应用中非常重要。相比传统的支架成形方法,基于离散—堆积原理的快速原型技术,所制造的支架个性化程度较高:支架的孔隙率、力学性能、生物相容性和降解特性等方面,可以通过参数设计和材料选择的方法进行人工设定;因此非常适于构建结构性的组织和器官。介绍了现有的基于快速原型的组织工程支架的成形技术,总结了其特点及应用现状,并分析讨论了其优缺点。     

Mechanical properties and in-vivo performance of calcium phosphate cement-chitosan fibre composite

Self-hardened calcium phosphate cement (CPC) sets to form hydroxyapatite and possesses excellent osteoconductivity. However, lack of macroporosity and low strength constrain its application in bone tissue engineering. Recent studies have incorporated various fibres into CPC to improve its mechanical strength. The present approach focused on the reinforcement of CPC with chitosan fibres and then the effects of the fibre structure on the mechanical properties and macrochannels formation characteristics of CPC-fibre composite were investigated. Chitosan fibres of diameter 200 microm were used to fabricate two types of three-dimensional structure, which were then coated with collagen and incorporated into CPC to fabricate CPC-fibre implants with a fibre volume content of 5 per cent. The compressive strength of the CPC-fibre implant was 33 MPa when the strain was 2.4 per cent, which is fourfold higher than that of the CPC control. Nine cylindrical implants including six CPC-fibre implants were implanted in the bone defects of nine dogs and were then post-operatively observed. After 20 weeks in vivo, new callus from the healthy tissue of the defect entirely integrated with the CPC-fibre implant and new bone was formed as the implant degraded. Scanning electronic microscopy images indicated that macrochannels were formed in the CPC-fibre implants with the degradation of fibres, but only micropores with a scale of less than 50 microm could be observed in the CPC control. Briefly, the incorporation of a suitable chitosan-fibre structure into a CPC implant not only could improve its mechanical properties but also facilitated the bone repair process in vivo.     

In-situ engineering of cartilage repair: a pre-clinical in-vivo exploration of a novel system

This investigation explores a new cartilage repair technique that uses a novel method to secure a non-woven multifilamentous scaffold in the defect site after microfracture. The hypothesis is that a scaffold provides a larger surface area for attachment and proliferation of the mesenchymal stem cells that migrate from the bone marrow. Two in-vivo studies were undertaken in an ovine model. The first study, which lasted for 8 weeks, aimed to compare the new technique with microfracture. Chondral defects, 7 mm in diameter, were created in both femoral medial condyles of five ewes. One defect was treated with the new technique while the contralateral knee was treated with microfracture alone. The results revealed that the quantity of repair tissue was significantly greater in the defects treated with the new system. The second study had two time points, 3 and 6 months, and used 13 ewes. In this study, both defects were treated with the new technique but one received additional subchondral drilling in order to stimulate extra tissue growth. The majority of the implants had good tissue induction, filling 50-100 per cent of the defect volume, while the compressive modulus of the repairs was in the range of 40-70 per cent of that for the surrounding cartilage. In addition, hyaline-like cartilage was seen in all the repairs which had the additional drilling of the subchondral bone.     

组织工程骨支架内部微孔结构流场特性分析

组织工程骨支架内部微孔结构对于营养液的渗入和细胞的长入有着至关重要的影响,也直接关系到支架是否能够代替缺损部位的骨骼,继续发挥其作用与功能。根据骨骼内部微孔结构的扫描电镜形貌设计三种微孔单胞模型,并利用ADINA有限元分析软件对组织工程骨支架微孔单胞模型内营养液的流动性能进行了数值模拟,得到不同类型微孔单胞模型内部流场的压力和速度分布,分析模型参数对营养液平均入口压力和流速的影响规律。结果表明：当营养液从微孔单胞模型的上端流入到下端流出时,最大压力均出现在入口部位且靠近单胞模型壁面处,营养液流速变化趋势是先增大后减少,且最大流速均出现在入口附近。随着连通孔径的增大,平均入口压力值减少,营养液流速值更大,且分布更均匀。对于带孔板-杆单胞和带孔板单胞而言,与连通孔径D相比,中心孔径D_s对平均入口压力和流速的影响很小。通过对比不同类型单胞模型,发现开口杆状单胞模型的平均入口压力更稳定,压力值更小,处于（0.300~0.412）Pa,且营养液流速更大,分布更均匀,且最大流速处于（0.011 8~0.013 1）m/s,更有利于营养液快速均匀渗入和细胞均匀的沉积。所取得的研究结果对组织工程骨支架内部微孔结构的优化设计、后续仿形建模的研究及快速成型制造奠定了基础。