组织工程化三维仿骨支架重建股骨头坏死区研究

首先研制出具有取向性类骨结构的β-TCP三维仿骨支架,经过仿生类骨处理和组织工程化后,植入犬的股骨头坏死区,30周后取出股骨头进行分析研究.与此同时开展了几种支架材料重建股骨头坏死区的力学性能分析和模拟.结果显示,具有取向性类骨结构的β-TCP三维仿骨支架具有很好的生物相容性和力学相容性.动物实验研究表明:组织工程化三维仿骨支架诱导生长出新的骨小梁,并伴有β-TCP降解,这为修复或重建股骨头局部坏死区提供了一种有希望的新途径.     

Fabrication of porous scaffolds for bone tissue engineering via low-temperature deposition

A new process of low-temperature deposition manufacturing (LDM) based on the layer-by-layer manufacturing method of solid freeform fabrication is proposed to fabricate poly(l-lactic acid)/(tricalcium phosphate) composite scaffolds for bone tissue engineering. The LDM system and the manufacturing process are analyzed. The manufactured scaffolds are evaluated as bone regeneration scaffolds.     

仿生纳米纤维支架促进骨组织再生

人口老龄化,疾病以及交通事故等造成大量的人体骨组织损伤和丢失。如何实现骨组织缺损的快速修复与再生成为临床医学研究的重要课题和目标,而生物医用材料在其中发挥着极其重要的作用。目前临床上常用的骨组织修复材料如自体骨、异体骨、合成材料（金属,陶瓷,高分子）等都存在各种各样的问题,无法实现大规模的应用和骨组织的快速有效再生。而骨组织工程学科研究多孔支架结合细胞和生长因子来实现骨组织再生,以鳃决骨科临床面临的问题为目的。最近十多年来,三维纳米纤维支架由于可以仿天然细胞外基质的结构和形态而显示出较强的促进细胞增殖、成骨分化以及骨组织修复再生的能力。主要综述具有仿生的纳米纤维及其复合支架材料的制备技术以及他们在增强细胞功能、干细胞成骨分化、及其骨组织再生中的应用。     

Engineering the biological performance of hierarchical nanostructured poly(ε-carpolactone) scaffolds for bone tissue engineering

Scaffolds play an important role as physical substrates for cell proliferation and differentiation, leading to tissue regeneration. For bone applications, researchers are focusing on cellular or acellular biocompatible biodegradable polymeric scaffolds. However, high biological performance scaffolds are still required to meet actual clinical demands. This paper discusses a novel strategy to engineer the biological performance of polymeric scaffolds through the combined use of additive manufacturing, acetone vapour annealing surface treatment and dopamine grafting, enabling the fabrication of hierarchical nanostructured tissue engineering structures. Produced scaffolds present improved biological behaviour compared to conventional additive manufactured scaffolds, and similar mechanical properties, showing high potential for clinical applications.     

钛合金变形Gyroid单元梯度多孔结构设计与分析

研究一种具有径向和轴向孔径梯度的变形Gyroid单元多孔结构参数化设计方法,采用激光选区熔化成形(selective laser melting, SLM)技术,制备出孔隙率为60%和75%的钛合金变形Gyroid单元梯度多孔结构样件。使用有限元法(finiteelementmethod,FEM)对4组梯度多孔支架模型及2组均质模型进行静力学仿真分析,对制备的钛合金梯度多孔样件进行力学性能测试,并与已测试过的均质样件进行力学性能对比分析。有限元计算结果与力学性能试验结果共同表明：变形Gyroid单元多孔结构力学性能随孔隙率的升高而降低,孔隙率相同时,径向梯度多孔支架力学性能优于均质多孔支架,更适用于皮质骨的骨缺损修复,轴向梯度多孔支架力学性能相比均质多孔支架有所减弱,更适用于松质骨。     

金属生物材料支架的微结构拓扑优化设计及选区激光熔化制造(英文)

生物材料支架的精确设计和制造是骨组织工程系统研究的基础。生物材料支架应该同时满足大孔隙率和与骨组织匹配的力学性能要求。这两个目标相互制约,大的孔隙率会降低其力学性能。利用拓扑优化的方法,在体积分数的约束下,寻求刚度最大的最优材料分布微结构。建立算法,得到了不同体积分数的2D和3D最优微结构,并提取3D拓扑优化的结果,然后将其转化为STL格式的CAD模型文件。微结构在三维方向整列成支架结构,通过选区激光熔化方法制造30%(体积分数)的Ti支架样品。从SEM图像看出,支架样品的结构和孔径与CAD模型基本一致,500μm微结构单元的平均孔径为231μm。复杂形状金属生物材料支架的精确制造证实了选区激光熔化技术在金属生物医学材料制造中的可行性。     

多孔钛骨组织工程支架设计及孔结构表征

针对目前骨组织工程支架微孔结构难以准确设计制备的问题,提出了一种基于点云的参数化建模+3D打印新方法。通过提取cube(C)、diamond(D)、gyroid(G)3种结构的型面函数点云数据,完成对不同孔结构特征的参数化建模。通过对模型有限元力学分析,对不同孔结构特征的多孔钛骨组织支架进行力学设计与订制。借助激光选区熔融(SLM)3D打印技术,完成对不同孔特征的骨组织支架快速成型。对多孔钛骨组织支架进行了相关材料学表征,包括孔结构表征与力学性能测试。结果表明:参数化模型的快速成型制造,能够有效地设计制备钛合金骨组织工程支架的孔结构特性,且可有效设计订制支架的力学性能,从仿生的角度实现多孔钛合金骨组织工程支架生物学功能的设计优化。     

Three-dimensional chitosan-nanohydroxyapatite composite scaffolds for bone tissue engineering

We describe the structure of biodegradable chitosan-nanohydroxyapatite (nHA) composites scaffolds and their interaction with pre-osteoblasts for bone tissue engineering. The scaffolds were fabricated via freezing and lyophilization. The nanocomposite scaffolds were characterized by a highly porous structure and pore size of ∼50–125 μm, irrespective of nHA content. The observed significant enhancement in the biological response of pre-osteoblast on nanocomposite scaffolds expressed in terms of cell attachment, proliferation, and widespread morphology in relation to pure chitosan points toward their potential use as scaffold material for bone regeneration.     

钽涂层多孔钛合金支架的制备与表征

钽金属是一种理想的医用金属材料,能够与人体软/硬组织发生整合。利用化学气相沉积方法,在可控多孔结构的Ti6Al4V合金支架表面沉积涂覆钽金属涂层,使其同时具备理想的三维孔隙结构和力学相容性,以及钽金属优异的生物学性能。研究结果显示,多孔钛合金支架表面涂层前后色泽发生明显变化,涂层后支架呈现钽金属色泽。扫描电镜和XRD分析进一步证明了多孔钛合金支架表面沉积物为钽金属。与美国Zimmer公司生产的多孔钽小梁金属相比,钽涂层多孔钛合金支架具备与人体皮质骨更相似的弹性模量和抗压强度,是一种理想的骨修复替代物。     

Calcium phosphate scaffolds for bone repair

Calcium phosphates, with their chemical similarity to bone mineral, show biocompatibility with hard and soft tissues and offer massive potential for bone repair, both as scaffolds to be implanted directly into the defect and as structures for cell transplantation or to guide new bone growth in tissue engineering. This paper reviews the requirements and motivation for synthetic bone graft alternatives and the production routes for, particularly, hydroxyapatite porous scaffolds. It also considers the important role of substitution of ions such as silicate into calcium phosphates so as to more closely mirror the chemistry of bone mineral and to elicit specific biological responses.     

Bioactive Ca-P scaffolds used for bone reconstruction

1　INTRODUCTIONSkeletalreconstructionorregenerationisre quiredincasesinvolvinglargedefectscreatedbytu morresection ,trauma ,andskeletalabnormalities .Graftsandflapsofautogenoustissuearetwoofthemostsuccessfulmeansofreconstructionbecausetheyallowthetransplantationofbonecontainingbioactivemolecules,livecells ,andfrequently ,avascularsup plythatallowthetransplanttosurviveandremodeleveninhostileradiatedenvironments .However ,onlyaminimalamountoftissuecanbeharvestedforauto grafts,anditisverydiff…     

Microstructure,Mechanical Properties and Corrosion Behavior of Porous Mg-6 wt.% Zn Scaffolds for Bone Tissue Engineering

Porous Mg-based scaffolds have been extensively researched as biodegradable implants due to their attractive biological and excellent mechanical properties. In this study, porous Mg-6 wt.% Zn scaffolds were prepared by powder metallurgy using ammonium bicarbonate particles as space-holder particles. The effects of space-holder particle content on the microstructure, mechanical properties and corrosion resistance of the Mg-6 wt.% Zn scaffolds were studied. The mean porosity and pore size of the open-cellular scaffolds were within the range 6.7-52.2% and 32.3-384.2 µm, respectively. Slight oxidation was observed at the grain boundaries and on the pore walls. The Mg-6 wt.% Zn scaffolds were shown to possess mechanical properties comparable with those of natural bone and had variable in vitro degradation rates. Increased content of space-holder particles negatively affected the mechanical behavior and corrosion resistance of the Mg-6 wt.% Zn scaffolds, especially when higher than 20%. These results suggest that porous Mg-6 wt.% Zn scaffolds are promising materials for application in bone tissue engineering.     

基于SLM的Ti-6Al-4V人工骨支架的结构设计

设计了6种Ti-6Al-4V人工骨支架,利用SLM(选择性激光熔化)进行制备。采用万能材料实验机结合高速摄像机分析支架的压缩过程,并利用Ansys进行分析。结果表明：支架的立柱直径对支架的力学性能参数影响较大,横梁直径对其影响较小;在相同高度下,支架横梁直径增大、层数增多或立柱直径增大,均使结构长径比减小,使结构稳固且支架承载能力提高;支架的力学性能应与周围骨组织相匹配,经过分析,3种结构的支架力学性能参数与人体股骨相近,故可作为股骨的人工骨支架。     

Biomanufacturing of customized modular scaffolds for critical bone defects

There is a significant unmet clinical need for modular and customized porous biodegradable constructs (scaffolds) for non-union large bone loss injuries. This paper proposes modelling and biomanufacturing of modular and customizable porous constructs for patient-specific critical bone defects. A computational geometry-based algorithm was developed to model modular porous constructs using a parametric femur model based on the frequency of common injuries. The generated modular constructs are used to generate biomimetic path planning for three-dimensional (3D) printing of modular scaffold pieces. The developed method can be used for regenerating bone tissue for treating non-union large bone defects.     

新型可降解生物医用镁合金JDBM的研究进展

镁合金因具有与人体骨头接近的密度和弹性模量、高比强度和比刚度、生物可降解性以及生物相容性等优点,近10年来国内外研究人员对其应用于骨内植物、骨组织工程支架和心血管支架等领域进行了广泛的研究。然而,目前大多数研究均以现有商用镁合金为对象,如含Al元素的AZ31、AZ91以及含重稀土元素的WE43等,并未考虑到作为生物材料的安全性等问题。本文作者阐述镁合金作为生物医用材料的优势、面临的挑战以及应对策略;重点介绍上海交通大学轻合金精密成型国家工程研究中心近年来围绕自行研发的新型生物医用镁合金JDBM开展的研究工作;最后展望可降解生物医用镁合金的应用前景和发展方向。     

3D凝胶打印制备用于松质骨工程的TCP多孔支架

通过3D凝胶打印（3DGP）技术制备了高强度和高孔隙率的磷酸三钙（TCP）多孔支架,通过扫描电子显微镜（SEM）观察支架的微观形态,并通过初步的动物实验评估了多孔支架的生物相容性。研究结果表明,适合打印的浆料固含量为34%（体积分数）,打印支架在长度、宽度和高度方向上的收缩率分别为11.44%±0.20%,9.41%±0.23%和10.57%±0.20%。当支架在1150 ℃下烧结2 h后,支架的抗压强度为22.6±0.12 MPa,孔隙率约为62.1%。初步的动物植入实验显示多孔TCP支架在兔股骨髁缺损处未引起明显的排斥反应,并在骨与支架的连接处未见炎症反应或慢性炎症反应。通过3DGP技术制备的多孔TCP支架具有良好的生物相容性和力学性能,有望满足松质骨的植入要求,为下一步的实验研究打下基础。     

新型多孔镁压缩性能的有限元分析

利用有限元方法建立了激光打孔制备的直孔型多孔镁样品的压缩模型,系统分析了孔隙率、孔径及孔的排布对多孔镁样品压缩性能的影响,初步探讨了多孔镁在压缩过程中的变形规律.模拟计算结果表明,随着孔隙率、孔径的增加和孔的排布角的减小,多孔镁压缩曲线下移,屈服强度和弹性模量随之下降;多孔镁的压缩变形规律符合金属的最小阻力定律.     

Novel fabrication of forsterite scaffold with improved mechanical properties

In this study, the macroporous forsterite scaffolds with highly interconnected spherical pores, with sizes ranged from 50 to 200 μm have been successfully fabricated via gelcasting method. The crystallite size of the forsterite scaffolds was measured in the range 26-35 nm. Total porosity of different bodies sintered at different sintering temperatures was calculated in the range 81-86%, while open porosity ranges from 69 to 78%. The maximum values of compressive strength and elastic modulus of the prepared scaffolds were found to be about 2.43 MPa and 182 MPa, respectively, which are close to the lower limit of the compressive strength and elastic modulus of cancellous bone and the compressive strength is equal to the standard for a porous bioceramic bone implant (2.4 MPa). Transmission electron microscopy analyses showed that the particle sizes are smaller than 100 nm. In vitro test in the simulated body fluid proved the good bioactivity of the prepared scaffold. It seems that, the mentioned properties could make the forsterite scaffold appropriate for tissue engineering applications, but cell culture and in vivo tests are needed for more confidence.     

The development of biocomposite nanofibers for tissue scaffolding applications

The last decade has seen significant progress in the production of nanofibers by electrospinning. One of the major drivers to this progress is the potential use of nanofibrous structures as scaffolds for engineering tissues in regenerative medicine. Electrospun fibers are capable of emulating the nanofibrous architecture of the native extracellular matrix. They can potentially provide in-vivo-like nanomechanical and physicochemical signaling cues to the cells to establish apposite cell-scaffold interactions and promote functional changes between and within cells toward synthesis of a genuine extracellular matrix over time. In this context, this paper presents a brief overview of a scaffold design strategy. It also presents recent research pertaining to developing biomimetic and bioactive nanofibrous tissue scaffolds through electrospinning biocomposite nanofibers of organic-organic and inorganic-organic hybrids, which are potentially applicable to soft and hard tissue engineering.     

Porous ceramic scaffolds with complex architectures

This work compares two novel techniques for the fabrication of ceramic scaffolds for bone tissue engineering with complex porosity: robocasting and freeze casting. Both techniques are based on the preparation of concentrated ceramic suspensions with suitable properties for the process. In robocasting, the computer-guided deposition of the suspensions is used to build porous materials with designed three dimensional geometries and microstructures. Freeze casting uses ice crystals as a template to form porous lamellar ceramic materials. Preliminary results on the compressive strengths of the materials are also reported.