生物活性人工骨结合CAD/CAM技术重建颅骨板制作系统

目的 通过CAD／CAM技术和快速成型技术并结合生物活性人工骨材料的应用，建立个性化设计制造具有良好骨融合性的颅骨板制作系统。方法 通过螺旋CT扫描、CAD三维重建成像、快速成型机加工，制成与患者颅骨缺损部位几何形态相同的个性化实体模型，应用石膏翻模工艺和EH复合人工骨材料，制成患者骨修补治疗用颅骨板。结果 CAD／CAM技术重建的人工骨颅骨板几何外形与骨缺损部位非常吻合，与健康侧对称，临床效果非常满意。结论 生物活性人工骨结合CAD／CAM技术重建颅骨板制作系统为治疗颅骨缺损患者提供了一种新手段，可有效提高临床治疗效果和修复美学效果。     

三维打印组织工程牙计算机辅助设计建模技术的应用

背景：国内外关于如何成功构建组织工程牙支架材料内部空间构型的文献报道较少。 目的：建立适用于组织工程牙需求的支架材料CAD空间构型及支架结构实体微观模型STL格式文件。 方法：采用MICRO CT对离体大鼠第二磨牙进行连续扫描,将MICRO CT获得的DICOM格式文件导入MIMICS软件,将生成的三维模型导入GEOMAGIC12软件,提取外层轮廓,利用偏移功能模拟得到大鼠磨牙外层轮廓数据。利用CATIA V5R17软件构建支架材料空间内部多孔微观模型单体,在空间合适坐标上阵列得到组织工程牙内部支架整体模型,通过变更单体构型还可快速建立多种整体支架构型。装配大鼠磨牙外层轮廓数据与内部空间支架得到三维打印组织工程牙CAD 模型STL文件。 结果与结论：成功建立了牙体组织支架微观结构CAD模型,该CAD STL模型可直接用于三维打印系统快速成型组织工程牙支架。说明基于结合计算机逆向与正向工程建模技术,可快速建立多种符合组织工程牙要求的支架材料空间构型。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程      

计算机辅助技术在骨关节疾病中的应用

背景：以往采用二维图像资料如X射线片、CT、MRI扫描等进行骨关节病手术设计,在反映骨关节病变严重程度、病变位置和畸形情况等方面不全面、欠准确,而且缺少直观性。 目的：研究计算机辅助设计和快速成型技术辅助骨关节伤病手术治疗的新方法。 方法：按反求工程的基本原理,采用医学CT/MRI扫描获取106例骨伤病患者骨骼二维图像资料,采用计算机辅助三维重建建立骨、关节解剖模型,将骨、关节解剖模型输入CAD软件进行精确分析,进一步采用快速成型技术制作骨关节原型进行实物原型分析,然后将骨关节解剖模型输入计算机进行外科手术过程设计、预演,选择合适的内固定材料,计算机辅助设计、快速成型技术制作外科手术辅助模板、个性化植入物等,最后精确实施骨关节外科手术。 结果与结论：31例骨关节畸形患者术后恢复良好的解剖外形和功能;17例前后交叉韧带损伤患者术后膝关节功能良好;31例骨折患者术后3~6个月获得骨折愈合;7例个性化假体和8例内固定重建肿瘤切除后骨缺损患者,随访期间未发现内固定器械断裂、假体松动和肿瘤复发;12例髋臼发育不良患者术后恢复正常髋臼包容和良好髋关节功能。提示计算机辅助技术可应用于骨关节畸形精确数字化矫形,设计个性化假体,辅助前后交叉韧带重建,疑难假体置换,辅助特殊疑难骨折、关节内骨折、陈旧性骨折复位、固定,骨肿瘤的个性化切除设计、结构与功能重建。     

定制式解剖接骨板系统固定Vancouver B Ⅰ型股骨假体周围骨折的生物力学分析

背景：目前锁定接骨板结合钢丝或钢缆治疗股骨假体周围骨折时近端常采用单皮质固定，稳定性不强，且接骨板近端与股骨无法达到解剖贴合，而定制式解剖接骨板系统(customized anatomical plate system,CAPS)可有效解决这一问题。目的：探讨CAPS固定Vancouver BⅠ型股骨假体周围骨折的生物力学强度。方法：选取1 006例股骨CT薄层扫描数据导入MIMICS 21.0版本软件中建立股骨三维重建模型，设为股骨三维重建组；选取56根完整的人体股骨标本设为股骨标本组，两组进行股骨解剖外形测量并进行结果比较，两组结果无明显差异则根据测量结果在MIMICS 21.0软件和NX11.0软件中设计CAPS大致外形；选取8对冰冻人体股骨制作Vancouver BⅠ型股骨假体周围骨折模型，双源CT薄层扫描左侧8根股骨假体周围骨折模型获取数据，将数据传入上述设计软件确定CAPS模型，再依托器械公司最终制作8套CAPS;8对骨折模型编号1-8，左侧采用CAPS固定(CAPS组)，右侧采用金属锁定接骨板系统-大型锁定板固定(爪钢板组)，L1-L4、R1-R4行垂直加载测试和垂直短周...     

计算机辅助设计在耳模制作中的应用

目的 建立一种更为高效安全的三维耳模制作方法.方法 耳背式助听器使用时,需配上按患者耳朵外形制作的耳膜.利用MIMICS医学影像三维重建软件和Solidworks三维建模软件对患者耳部CT图像进行处理,建立耳模实体模型.结果 与传统方法制作的耳模相比,计算机辅助设计制作的耳模更加符合人体结构.结论 计算机辅助设计制作方法可更加安全、方便、快捷地制作耳模.     

计算机辅助组织工程在组织支架仿生建模和设计中的应用

计算机辅助组织工程(CATE)可以帮助进行复杂组织支架的建模,设计和制造,使很多用于改善替代材料力学及生物学性能的新方法得以实施。CATE通过获取组织的生物学、生物力学及生物化学信息,进行界面的设计、模拟和组织的制作。本文将讲述CATE在骨组织工程支架仿生设计中的应用:介绍运用CATE进行仿生建模,解剖结构重建,组织支架设计,定量CT分析,有限元分析和支架的自由挤压沉积制作。     

PC机上基于CT、MRI图像构建的颌面部三维数字模型

背景：近年来国内外学者对个人PC机上重建颌面部骨组织、皮肤、肌肉三维可视化模型进行了大量研究,但对于建立颌面部骨骼、皮肤、肌肉、血管的整体三维可视化模型尚无报道。 目的：利用螺旋 CT、MRI 数据及三维重建软件,在普通 PC 机建立颌面部整体的三维可视化模型。 方法：选择1名健康成年男性作为建模对象,分别通过螺旋CT、核磁共振扫描,得到样本的DICOM标准图像。将所有CT、MRI图像导入Mimics,建立颌面部骨骼、部分咀嚼肌、三叉神经池、颈内动脉、颈内静脉的三维可视化模型。选择颌面部骨骼三维模型为基准,将由MRI图像建立的肌肉、血管、三叉神经池模型导入,进行三维模型空间配准。最终得到颌面部整体的三维可视化模型。 结果与结论：成功建立了颌面部骨骼、肌肉、皮肤、三叉神经池、血管的整体三维模型,准确反映了颌面部复杂的解剖结构,可为临床诊断提供可靠的解剖资料,并为今后的模拟手术打下良好的基础。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

基于计算机CAD/CAE的个体化人工膝关节假体的设计

目的探索一条利用CAD／CAE技术进行个体化人工膝关节假体设计的可行途径，内容涉及从患膝CT数据读取、三维重建，到假体设计，直至虚拟于术和假体应力状态评价整个流程，从而为个体化膝关节的设计以及手术策划提供一定的指导意义。方法①识别并读取患者病变膝关节CT数据；②运用逆向技术进行膝关节三维重建；③借助计算机辅助设计（CAD）技术进行个体化膝关节假体的设计；④利用计算机虚拟装配技术进行膝关节假体虚拟手术安装、系统运动功能评价；⑤对假体应力状态进行CAE分析。结果基于患者膝关节解剖形态的研究，运用CAD／CAE技术，立足于膝关节假体生物力学性、功能性、稳定性、可靠性及耐用性的设计原则，完成了个体化膝关节假体的设计输出；探索了利用CAD／CAE技术进行个体化人工膝关节假体设计巾从数据读取到产品验证的整个流程。结论CAD评估及虚拟手术证明该设计结构是可行的；CAE计算机辅助分析证明假体的几何尺寸是合理的；该设计流程是切实可行的，它不仅对产品设计甚至对于术的策划具有较强的指导意义。     

3D膝关节模型的构建

背景:三维图像重建是开展膝关节虚拟研究的基础。关节周围韧带、软骨、半月板等结构分割重建报道较少。目的:在前期大量膝关节标本解剖研究的基础上,利用CT及MRI数据,三维重建包括关节周围韧带、软骨、半月板等结构在内的膝关节模型。方法:采用1例人体成年膝关节标本CT、MRI薄层扫描数据,导入Mimics 10.01分别三维重建膝关节骨、软骨、韧带及半月板等结构,利用逆向工程软件Geomagic 8进行及图像配准处理。结果与结论:三维重建了包括关节周围韧带、软骨、半月板等结构在内的膝关节模型,为建立相应膝关节有限元模型奠定了基础。     

甲状软骨成形术的三维有限元仿真模拟

运用Mimics医学重构软件,对喉的甲状软骨进行三维重建,研究不同的支架材料对甲状软骨成形术当中开窗部位的影响,为接下来人工软骨支架的材料遴选和制备提供理论依据。首先将标准DICOM格式的CT图像导入到Mimics10.1医学三维重建软件中,进行图像的去噪、分割和区域生长等处理,建立起甲状软骨的三维模型;然后将生成的几何模型导入到逆向工程软件Geomagic Studio12.0中,对三维模型进行曲面拟合,建立NURBS曲面实体模型,再通过Geomagic Studio软件中的CAD模块,完成甲状软骨的开窗和支架的植入;最后在ANSYS Workbench14.0中对不同支架的修复情况进行数值模拟,比较修复过后的甲状软骨的生物力学性质。最终建立的三维实体模型外形轮廓上与真实甲状软骨具有较好的几何相似性,开窗的部位和大小与临床上保持一致。软骨模拟受力过程也和术后进行效果评价方法在力学性能上相类似。数值模拟阶段的结果为临床上开窗部位的固定和修复材料的筛选提供依据。     

制备软骨组织工程支架的方法

背景：软骨组织工程支架作为软骨细胞外基质的替代物,其外形和孔结构对实现其作用和功能具有非常重要的意义。 目的：回顾目前若干种常用软骨组织工程中三维多孔支架的制备方法。 方法：由第一作者检索2000至2013年PubMed数据库,ELSEVIER SCIENCEDIRECT、万方数据库、中国知网数据库。英文检索词为“Cartilage tissue engineering;scaffolds;fabrication”,中文检索词为“软骨组织工程;制备方法;支架材料;多孔支架”。 结果与结论：制备软骨组织工程支架的方法有相分离/冷冻干燥法、水凝胶技术、快速成型技术、静电纺丝法、溶剂浇铸/粒子沥滤法及气体发泡法等。目前研究发现,支架中孔径的大小对组织的重建有着直接的影响,孔径为100-250 μm的孔有益于骨及软骨组织的再生。通过溶液浇铸/粒子沥滤法、气体发泡法所制备的支架孔径大小在这一范围内,因此比较适合用于骨、软骨组织工程支架的构建。研究人员通常将多种方法结合起来,以期能制备出生物和力学性能方面更加仿生的组织工程多孔支架。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

Macroporous elastomeric scaffolds with extensive micropores for soft tissue engineering

Macroporous scaffolds are of great value in tissue engineering. We have developed a method to fabricate macroporous scaffolds from a biocompatible and biodegradable elastomer, poly(glycerol sebacate) (PGS). This method is potentially very useful for soft tissue engineering. Our fabrication method produced macroporous scaffolds with extensive micropores. We fabricated flat scaffolds and tubular scaffolds of uniform thickness. This fabrication method demonstrated good control of variables such as pore size, porosity, and pore interconnectivity. Sodium chloride (salt) crystals, which served as solid porogens, were packed into a mold and fused in a humid chamber. PGS was cured while dispersed throughout the fused salt template. Dissolution of the salt and subsequent lyophilization produced elastomer sponges with approximately 90% porosity, interconnected macropores (75-150 microm), and extensive micropores (5-20 microm). The macropores were generated by the salt particles, while the micropores were likely generated by glycerol vapor formed during PGS curing. Such numerous micropores could facilitate cell-cell interactions and mass transport. Fibroblasts adhered to and proliferated well within the PGS scaffolds and formed three-dimensional tissue-engineered constructs within 8 days.     

Porogen-based solid freeform fabrication of polycaprolactone-calcium phosphate scaffolds for tissue engineering

Drop on demand printing (DDP) is a solid freeform fabrication (SFF) technique capable of generating microscale physical features required for tissue engineering scaffolds. Here, we report results toward the development of a reproducible manufacturing process for tissue engineering scaffolds based on injectable porogens fabricated by DDP. Thermoplastic porogens were designed using Pro/Engineer and fabricated with a commercially available DDP machine. Scaffolds composed of either pure polycaprolactone (PCL) or homogeneous composites of PCL and calcium phosphate (CaP, 10% or 20% w/w) were subsequently fabricated by injection molding of molten polymer-ceramic composites, followed by porogen dissolution with ethanol. Scaffold pore sizes, as small as 200 microm, were attainable using the indirect (porogen-based) method. Scaffold structure and porosity were analyzed by scanning electron microscopy (SEM) and microcomputed tomography, respectively. We characterized the compressive strength of 90:10 and 80:20 PCL-CaP composite materials (19.5+/-1.4 and 24.8+/-1.3 Mpa, respectively) according to ASTM standards, as well as pure PCL scaffolds (2.77+/-0.26 MPa) fabricated using our process. Human embryonic palatal mesenchymal (HEPM) cells attached and proliferated on all scaffolds, as evidenced by fluorescent nuclear staining with Hoechst 33258 and the Alamar Blue assay, with increased proliferation observed on 80:20 PCL-CaP scaffolds. SEM revealed multilayer assembly of HEPM cells on 80:20 PCL-CaP composite, but not pure PCL, scaffolds. In summary, we have developed an SFF-based injection molding process for the fabrication of PCL and PCL-CaP scaffolds that display in vitro cytocompatibility and suitable mechanical properties for hard tissue repair.     

Effect of conditioning methods on the microtensile bond strength of phosphate monomer-based cement on zirconia ceramic in dry and aged conditions

Scaffold fabrication for regenerating functional human tissues has an important role in tissue engineering, and there has been much progress in research on scaffold fabrication. However, current methods are limited by the mechanical properties of existing biodegradable materials and the irregular structures that they produce. Recently, several promising biodegradable materials have been introduced, including poly(propylene fumarate) (PPF). The development of micro-stereolithography allows the fabrication of free-form 3D microstructures as designed. Since this technology requires a low-viscosity resin to fabricate fine structures, we reduced the viscosity of PPF by adding diethyl fumarate. Using our system, the curing characteristics and material properties of the resin were analyzed experimentally. Then, we fabricated waffle shape and 3D scaffolds containing several hundred regular micro pores. This method controlled the pore size, porosity, interconnectivity, and pore distribution. The results show that micro-stereolithography has big advantages over conventional fabrication methods. In addition, the ultimate strength and elastic modulus of the fabricated scaffolds were measured, and cell adhesion to the fabricated scaffold was observed by growing seeded cells on it. These results showed that the PPF/DEF scaffold is a potential bone scaffold for tissue engineering.     

Sintering and robocasting of beta-tricalcium phosphate scaffolds for orthopaedic applications

beta-Tricalcium phosphate (beta-TCP) scaffolds with designed, three-dimensional (3-D) geometry and mesoscale porosity have been fabricated by direct-write assembly (robocasting) techniques. Concentrated beta-TCP inks with suitable viscoelastic properties were developed to enable the fabrication of the complex 3-D structures. A comprehensive study of the sintering behavior of TCP as a function of the calcium content in the starting powder was also carried out, and the optimal heat treatment for fabricating scaffolds with dense beta-TCP rods has been determined. Such analysis provides clues to controlling the microstructure of the fabricated structures and, therefore, enabling the fabrication by robocasting of TCP scaffolds with tailored performance for bone tissue engineering applications.     

A simple method for fabricating 3-D multilayered composite scaffolds

One limitation of electrospinning stems from the charge build-up that occurs during processing, preventing further fibre deposition and limiting the scaffold overall thickness and hence their end-use in tissue engineering applications targeting large tissue defect repair. To overcome this, we have developed a technique in which thermally induced phase separation (TIPS) and electrospinning are combined. Thick three-dimensional, multilayered composite scaffolds were produced by simply stacking individual polycaprolactone (PCL) microfibrous electrospun discs into a cylindrical holder that was filled with a 3% poly(lactic-co-glycolic acid) (PLGA) solution in dimethylsulfoxide (a good solvent for PLGA but a poor one for PCL). The construct was quenched in liquid nitrogen and the solvent removed by leaching out in cold water. This technique enables the fabrication of scaffolds composed principally of electrospun membranes that have no limit to their thickness. The mechanical properties of these scaffolds were assessed under both quasi-static and dynamic conditions. The multilayered composite scaffolds had similar compressive properties to 5% PCL scaffolds fabricated solely by the TIPS methodology. However, tensile tests demonstrated that the multilayered construct outperformed a scaffold made purely by TIPS, highlighting the contribution of the electrospun component of the composite scaffold to enhancing the overall mechanical property slate. Cell studies revealed cell infiltration principally from the scaffold edges under static seeding conditions. This fabrication methodology permits the rapid construction of thick, strong scaffolds from a range of biodegradable polymers often used in tissue engineering, and will be particularly useful when large dimension electrospun scaffolds are required.     

3D fiber-deposited scaffolds for tissue engineering: influence of pores geometry and architecture on dynamic mechanical properties

One of the main issues in tissue engineering is the fabrication of scaffolds that closely mimic the biomechanical properties of the tissues to be regenerated. Conventional fabrication techniques are not sufficiently suitable to control scaffold structure to modulate mechanical properties. Within novel scaffold fabrication processes 3D fiber deposition (3DF) showed great potential for tissue engineering applications because of the precision in making reproducible 3D scaffolds, characterized by 100% interconnected pores with different shapes and sizes. Evidently, these features also affect mechanical properties. Therefore, in this study we considered the influence of different structures on dynamic mechanical properties of 3DF scaffolds. Pores were varied in size and shape, by changing fibre diameter, spacing and orientation, and layer thickness. With increasing porosity, dynamic mechanical analysis (DMA) revealed a decrease in elastic properties such as dynamic stiffness and equilibrium modulus, and an increase of the viscous parameters like damping factor and creep unrecovered strain. Furthermore, the Poisson's ratio was measured, and the shear modulus computed from it. Scaffolds showed an adaptable degree of compressibility between sponges and incompressible materials. As comparison, bovine cartilage was tested and its properties fell in the fabricated scaffolds range. This investigation showed that viscoelastic properties of 3DF scaffolds could be modulated to accomplish mechanical requirements for tailored tissue engineered applications.     

Rapid prototyping of tissue-engineering constructs, using photopolymerizable hydrogels and stereolithography

One of the most important aspects of tissue engineering is the design of the scaffold providing the mechanical strength and access to nutrients for the new tissue. For customized tissue engineering, it is essential to be able to fabricate three-dimensional scaffolds of various geometric shapes, in order to repair defects caused by accidents, surgery, or birth. Rapid prototyping or solid free-form fabrication (SFF) techniques hold great promise for designing three-dimensional customized scaffolds, yet traditional cell-seeding techniques may not provide enough cell mass for larger constructs. This article presents a novel attempt to fabricate three-dimensional scaffolds, using hydrogels combined with cell encapsulation to fabricate high-density tissue constructs. A commercially available stereolithography technique was applied to fabricate scaffolds using poly(ethylene oxide) and poly(ethylene glycol)dimethacrylate photopolymerizable hydrogels. Mechanical characterization shows the constructs to be comparable with soft tissues in terms of elasticity. High cell viability was achieved and high-density constructs fabricated.     

Solid freeform fabrication of designer scaffolds of hyaluronic acid for nerve tissue engineering

The field of tissue engineering and regenerative medicine will tremendously benefit from the development of three dimensional scaffolds with defined micro- and macro-architecture that replicate the geometry and chemical composition of native tissues. The current report describes a freeform fabrication technique that permits the development of nerve regeneration scaffolds with precisely engineered architecture that mimics that of native nerve, using the native extracellular matrix component hyaluronic acid (HA). To demonstrate the flexibility of the fabrication system, scaffolds exhibiting different geometries with varying pore shapes, sizes and controlled degradability were fabricated in a layer-by-layer fashion. To promote cell adhesion, scaffolds were covalently functionalized with laminin. This approach offers tremendous spatio-temporal flexibility to create architecturally complex structures such as scaffolds with branched tubes to mimic branched nerves at a plexus. We further demonstrate the ability to create bidirectional gradients within the microfabricated nerve conduits. We believe that combining the biological properties of HA with precise three dimensional micro-architecture could offer a useful platform for the development of a wide range of bioartificial organs.     

Development of dual scale scaffolds via direct polymer melt deposition and electrospinning for applications in tissue regeneration

The objective of this study was the fabrication of highly functionalized polymeric three-dimensional (3D) structures characterized by nano and microfibers for use as an extracellular matrix-like tissue engineering scaffold. A hybrid process utilizing direct polymer melt deposition (DPMD) and an electrospinning method were employed to obtain the structure. Each microfibrous layer of the scaffold was built using the DPMD process in accordance with computer-aided design modeling data considering some structural points such as pore size, pore interconnectivity and fiber diameter. Between the layers of the three-dimensional structure, polycaprolactone/collagen nanofiber matrices were deposited via an electrospinning process. To evaluate the fabricated scaffolds, chondrocytes were seeded and cultured within the developed scaffolds for 10 days, and the levels of cell adhesion and proliferation were monitored. The results showed that the polymeric scaffolds with nanofiber matrices fabricated using the proposed hybrid process provided favorable conditions for cell adhesion and proliferation. These conditions can be attributed to enhanced cytocompatibility of the scaffold due to surficial nanotopography in the scaffold, chemical composition by use of a functional biocomposite, and an enlarged inner surface of the structure for cell attachment and growth.