计算机辅助仿生骨组织支架建模方法研究
摘要
在计算机辅助组织工程中,骨组织支架的设计和制造技术是整个骨组织工程研究领域的核心。在三维骨组织支架的设计中,合理的孔隙率、孔隙大小是骨组织建模必须考虑的关键要素。本文针对骨组织支架应该满足的基本要求,提出了一种骨组织支架建模的新方法,在VC++6.0平台上开发了骨组织支架设计的软件,为骨组织支架的设计和制造提供了理论依据。
本文的主要工作包括:
(1)通过对骨组织支架的作用、需满足的性能要求及骨组织的显微图像灰度图进行分析,确定了组织支架建模的方法,并结合快速原型技术给出了骨组织支架建模的技术路线。
(2)以孔隙率及孔隙大小作为目标参数,设计了支架内部的微孔结构,开发了可以任意设定孔隙率及孔隙率大小的微单元体模型。
(3)开发了可以处理多连通体的复杂轮廓的分层算法,并且对构成切层轮廓线的线段按照一定的规律进行了排序。考虑到支架外轮廓切层中可能遇到的各种复杂形状,给出了微单元体截面片填充的算法,得到了既包括组织支架轮廓信息又包括其内部信息的数据。
(4)利用OpenGL技术在VC++平台上开发出了骨组织支架建模的软件。以孔隙率及孔隙大小为目标参数,生成具有与人体骨相似的外轮廓切层及微孔结构填充的模型。实现了孔隙率在切层方向上任意调节。程序中还实现了与快速原型设备的CLI格式的接口文件,可以直接用来加工组织工程支架。
The design and manufacture technology of porous scaffold are the important research field in the bone tissue engineering. The suitable porosity and pore size are the key elements for scaffold modeling in the design of 3D bone tissue scaffolds. In this paper, a new method for scaffold modeling is presented based on the basic requirement of the bone tissue scaffold, a software to design bone tissue scaffold is developed on the VC++6.0 platform, which provides theoretical bases for developing and exploiting bone tissue scaffold.
The main works include:
By analyzing the functions, performance requirement and micro grey image of the human bone, the tissue scaffold modeling method which faced on rapid prototyping manufacturing is identified.
The micro-unit of the internal scaffold and the micro-unit model are developed which aiming at the appropriate pore size and porosity.
The slicing algorithm is developed which can handle the complicated 3D model such as multi-connected solid, and the slicing contour lines are sorted according to certain order. Taking into account all the complex shapes may encounter, micro-unit filling algorithm in 2D slicing is developed. The tissue scaffold data is obtained, which includes both the surface contour and the internal architecture information.
Using OpenGL technology, a software of scaffold bionic design is developed on the platform of VC++6.0. Take the pore size and the porosity as the main parameters, generating the surface slicing model and the micro-unit slicing model. According to different requirement, the porosity and the pore size can be adjusted in the slicing direction. CLI interface format file also be developed, which can be used in RP manufacturing.
本文的主要工作包括:
(1)通过对骨组织支架的作用、需满足的性能要求及骨组织的显微图像灰度图进行分析,确定了组织支架建模的方法,并结合快速原型技术给出了骨组织支架建模的技术路线。
(2)以孔隙率及孔隙大小作为目标参数,设计了支架内部的微孔结构,开发了可以任意设定孔隙率及孔隙率大小的微单元体模型。
(3)开发了可以处理多连通体的复杂轮廓的分层算法,并且对构成切层轮廓线的线段按照一定的规律进行了排序。考虑到支架外轮廓切层中可能遇到的各种复杂形状,给出了微单元体截面片填充的算法,得到了既包括组织支架轮廓信息又包括其内部信息的数据。
(4)利用OpenGL技术在VC++平台上开发出了骨组织支架建模的软件。以孔隙率及孔隙大小为目标参数,生成具有与人体骨相似的外轮廓切层及微孔结构填充的模型。实现了孔隙率在切层方向上任意调节。程序中还实现了与快速原型设备的CLI格式的接口文件,可以直接用来加工组织工程支架。
The design and manufacture technology of porous scaffold are the important research field in the bone tissue engineering. The suitable porosity and pore size are the key elements for scaffold modeling in the design of 3D bone tissue scaffolds. In this paper, a new method for scaffold modeling is presented based on the basic requirement of the bone tissue scaffold, a software to design bone tissue scaffold is developed on the VC++6.0 platform, which provides theoretical bases for developing and exploiting bone tissue scaffold.
The main works include:
By analyzing the functions, performance requirement and micro grey image of the human bone, the tissue scaffold modeling method which faced on rapid prototyping manufacturing is identified.
The micro-unit of the internal scaffold and the micro-unit model are developed which aiming at the appropriate pore size and porosity.
The slicing algorithm is developed which can handle the complicated 3D model such as multi-connected solid, and the slicing contour lines are sorted according to certain order. Taking into account all the complex shapes may encounter, micro-unit filling algorithm in 2D slicing is developed. The tissue scaffold data is obtained, which includes both the surface contour and the internal architecture information.
Using OpenGL technology, a software of scaffold bionic design is developed on the platform of VC++6.0. Take the pore size and the porosity as the main parameters, generating the surface slicing model and the micro-unit slicing model. According to different requirement, the porosity and the pore size can be adjusted in the slicing direction. CLI interface format file also be developed, which can be used in RP manufacturing.
引文
1 Langer R. Tissue engineering: a new field and its challenges [J]. Sci Am, 1999, 280: 86-89
2 Felicity R. A. J. Rose and Richard O. C. Oreffo. Breakthroughs and views bone tissue engineering: Hope vs Hype. Biochemical and biophysical research communications, 2002, 292(1):1~7
3 MiJung K, Yu S. C, Seung H. Y. Muscle regeneration by adipose tissue-derived adult stem cells attached to injectable PLGA spheres. Biochemical and Biophysical Research Communications, 2006, 348:384~392
4 Yuan L, Fumihiko S, Xinwen W, Akimichi T. Reconstruction of a tissue-engineering skin containing melanocytes. Cell Biology International, 2007, 31:985~990
5史廷春,张人佶,颜永年,卢清萍.快速成形外耳软骨支架.机械科学与技术, 2003, 22(3):477~479
6 Nesic D, Whiteside R, Brittberg M, Wendt D. Cartilage tissue engineering for degenerative joint disease. Advanced Drug Delivery Reviews, 2006, 58:300~322
7 Meyer U, Runte C, Dirksen D, Stamm R. Image-based biomimetric approach to design and fabrication of tissue engineered bone. International Congress Series, 2003, 1256:726~732
8 Qi-Zhi C, Kurosch R, Virginie F. Surface functionalization of Bioglass-derived porous scaffolds. Acta Biomaterialia, 2007, 3(4):503~514
9 Fong P, Shinoka Lopez-Soler T. I, Breuer C. The use of polymer based scaffolds in tissue-engineering heart valves. Progress in Pediatric Cardiology, 2006, 21:193~199
10 Stephanie M, Willerth, Shelly E. Sakiyama E. Approaches to neural tissueengineering using scaffolds for drug delivery. Advanced Drug Delivery Reviews, 2007, 59:325~338
11 Jie L, William C, Regli, Sun W. An approach to intergrating shape and biomedical attributes in vascular models. Computer-Aided Design, 2007, 39:598~609
12 Wei S, Andrew D, Binil S and Jae N. Computer-aided tissue engineering:overview, scope and challenges. Biotechnol. Appl. Biochem, 2004, 39:29-47.
13 Guldberg R. E, Ballock R. T, Boyan B.D. Analyzing Bone, Blood Vessels, and Biomaterials with Microcomputed Tomography. IEEE Engineering in Medicine and Biology Magazine, 2003, 77~83
14 Joerg. K, Tessmar, Achim M, Gopferich. Matrices and scaffolds for protein delivery in tissue engineering. Advanced Drug Delivery Reviews, 2007, 59:274~291
15 Guoping C, Takashi U, Tetsuya T. Scaffold Design for Tissue Engineering. Material Bioscience, 2002, 2:67-77
16吴林波,丁建东.组织工程三维多孔支架的制备方法和技术进展.功能高分子学报, 2003, 16(1):91~95
17 Dietmar W. Hutmacher. Scaffolds in tissue engineering bone and cartilage. Biomaterials, 2000, 20:2529~2543
18 Antonios G. Mikos, Amy J. Thorsen, Lisa A.Robert Langer. Preparation and characterization of poly(L-lactic acid) foams. Polymer, 1994, 35(5):1068~1077
19陈际达,崔磊,刘伟,曹谊林.溶剂浇铸/颗粒沥滤技术制备组织工程支架材料.中国生物工程杂志, 2003, 23(4):32~35
20 Wang K, Thomas C. H, Healy K. E, Nuber G. A novel method to fabricate bioabsorbable scaffolds. Polymer, 1995, 36:837-42.
21 Vladimir M, Thomas B, Thomas T, Gabor F and Toger R. Markwald. Organ printing: computer-aided jet-based 3D tissue engineering. Trends in biotechnology, 2003, 21(4):157~161
22 Hui K, Chen K.B. Modeling of the scaffold fabrication process for tissue engineering applications. CCECE/CCGEI, Saskatoon, 2005, 1255~1261
23 Iwan Z, Dietmar W. Hutmacher, Kim C. T, Swee H. T. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials, 2003, 24(24):1169~1185
24赵萍,蒋华,周芝庭.熔融沉积快速成形工艺的原理及过程.机械制造与研究, 2003, (5):17~23
25张剑锋,张建华,赵剑锋.激光快速成形制造技术的应用研究进展.航空制造技术, 2002, (7):34~37
26 Tan K. H, Chua C. K, Leong K. F. Scaffold development using selective laser sintering of polyetheretherketone–hydroxyapatite biocomposite blends.Biomaterials, 2003, 24(18):3115~3123
27陈步庆,林柳兰,陆齐,胡庆夕.三维打印技术及系统研究.机电一体化, 2005, 4:13~15
28张爱英,王连才,刘厚利,魏宏亮,冯增国.基于快速成形技术的组织工程支架制备进展.化工进展, 2004, 23(3):267~271
29陈中中,李涤尘,卢秉恒.气压式熔融沉积快速成形系统.电加工与模具, 2002, (2):9~12
30陈中中,早热木,李涤尘,卢秉恒,孙明林.利用快速成形技术制造人工生物活性骨.西安交通大学学报, 2003, 37(3):273~276
31颜永年,崔福斋,张人佶,胡蕴玉.人工骨的快速成形制造.材料导报, 2002, 14(2):11~13
32吴懋亮,周克平.选择性激光烧结方法加工仿生支架的工艺研究。中国制造业信息化, 2006, 36(3):35~38
33郑卫国,颜永年,熊卓.复合材料梯度结构组织工程支架建模方法.材料导报, 2002, 16(11):58~61
34陈立峰,颜永年,郑卫国,熊卓,张人佶.生物材料快速成形设备的设计与实现.设计与研究, 2003, 5:21~23
35 Chua C K, Leong K F, Cheah C M, et al. Development of a tissue engineering scaffold structure library for rapid prototyping. Part 2: Parametric library and assembly program. Advanced Manufacturing Technology, 2003, 21(4): 302~312
36李祥,李涤尘,张彦东,卢秉恒.骨组织微结构观察分析及仿生支架立体光固化间接制造.北京生物医学工程, 2006, 25(2):164~167
37王林,王臻,李祥,李涤尘等.大块组织工程骨支架结构设计制造及与人成骨细胞联合培养观察。中国矫形外科杂志, 2005, 13(5):376~379
38丁焕文,唐春雷,赵中岳等.个体化组织工程支架CAD设计与RP制作的方法的研究.生物骨科材料与临床研究, 2005, 2(1):1~4
39 Starly. B, Lau.W, Bradbury. T, Sun W. Internal architecture design and freeform fabrication of tissue replacement structures. Computer-Aided Design, 2006, 38:115~124
40陈作炳.人工关节CAD/CAM相关理论及其关键技术研究.武汉理工大学博士论文, 2004:63~75
41 Peter X. Ma. Scaffolds for tissue fabrication. Materials Today, 2004, 5:30~40
42毛娅,陈作炳,余新明,绕嵩.基于医学图像的人工骨三维仿生设计.中国体视学与图像分析, 2004, 9(3):160~164
43 Sun W. Binil S, Andrew D and Connie G. Computer-aided tissue engineering: application to biomimetic modeling and design of tissue scaffolds. Biotechnol Appl Chem, 2004, 39:49~58
44李莉敏,郭桂芳,胡庆夕,吴懋亮.面向骨组织工程的三维仿生支架的微观结构研究.中国制造业信息化. 2005, 34(4):86~88
45陈绪兵,叶献方,黄树槐.快速成形领域中的直接切片研究.中国机械工程, 2002, 13(7):71~73
46孙玉文,刘伟军,刘健. CAD/RP系统间数据模型的转换方法与发展.航空精密制造技术, 2001, 37(2):19~22
47李占利.基于STL的快速分层处理软件的研发.西安科技学院学报, 2001, 21(3):263~267
2 Felicity R. A. J. Rose and Richard O. C. Oreffo. Breakthroughs and views bone tissue engineering: Hope vs Hype. Biochemical and biophysical research communications, 2002, 292(1):1~7
3 MiJung K, Yu S. C, Seung H. Y. Muscle regeneration by adipose tissue-derived adult stem cells attached to injectable PLGA spheres. Biochemical and Biophysical Research Communications, 2006, 348:384~392
4 Yuan L, Fumihiko S, Xinwen W, Akimichi T. Reconstruction of a tissue-engineering skin containing melanocytes. Cell Biology International, 2007, 31:985~990
5史廷春,张人佶,颜永年,卢清萍.快速成形外耳软骨支架.机械科学与技术, 2003, 22(3):477~479
6 Nesic D, Whiteside R, Brittberg M, Wendt D. Cartilage tissue engineering for degenerative joint disease. Advanced Drug Delivery Reviews, 2006, 58:300~322
7 Meyer U, Runte C, Dirksen D, Stamm R. Image-based biomimetric approach to design and fabrication of tissue engineered bone. International Congress Series, 2003, 1256:726~732
8 Qi-Zhi C, Kurosch R, Virginie F. Surface functionalization of Bioglass-derived porous scaffolds. Acta Biomaterialia, 2007, 3(4):503~514
9 Fong P, Shinoka Lopez-Soler T. I, Breuer C. The use of polymer based scaffolds in tissue-engineering heart valves. Progress in Pediatric Cardiology, 2006, 21:193~199
10 Stephanie M, Willerth, Shelly E. Sakiyama E. Approaches to neural tissueengineering using scaffolds for drug delivery. Advanced Drug Delivery Reviews, 2007, 59:325~338
11 Jie L, William C, Regli, Sun W. An approach to intergrating shape and biomedical attributes in vascular models. Computer-Aided Design, 2007, 39:598~609
12 Wei S, Andrew D, Binil S and Jae N. Computer-aided tissue engineering:overview, scope and challenges. Biotechnol. Appl. Biochem, 2004, 39:29-47.
13 Guldberg R. E, Ballock R. T, Boyan B.D. Analyzing Bone, Blood Vessels, and Biomaterials with Microcomputed Tomography. IEEE Engineering in Medicine and Biology Magazine, 2003, 77~83
14 Joerg. K, Tessmar, Achim M, Gopferich. Matrices and scaffolds for protein delivery in tissue engineering. Advanced Drug Delivery Reviews, 2007, 59:274~291
15 Guoping C, Takashi U, Tetsuya T. Scaffold Design for Tissue Engineering. Material Bioscience, 2002, 2:67-77
16吴林波,丁建东.组织工程三维多孔支架的制备方法和技术进展.功能高分子学报, 2003, 16(1):91~95
17 Dietmar W. Hutmacher. Scaffolds in tissue engineering bone and cartilage. Biomaterials, 2000, 20:2529~2543
18 Antonios G. Mikos, Amy J. Thorsen, Lisa A.Robert Langer. Preparation and characterization of poly(L-lactic acid) foams. Polymer, 1994, 35(5):1068~1077
19陈际达,崔磊,刘伟,曹谊林.溶剂浇铸/颗粒沥滤技术制备组织工程支架材料.中国生物工程杂志, 2003, 23(4):32~35
20 Wang K, Thomas C. H, Healy K. E, Nuber G. A novel method to fabricate bioabsorbable scaffolds. Polymer, 1995, 36:837-42.
21 Vladimir M, Thomas B, Thomas T, Gabor F and Toger R. Markwald. Organ printing: computer-aided jet-based 3D tissue engineering. Trends in biotechnology, 2003, 21(4):157~161
22 Hui K, Chen K.B. Modeling of the scaffold fabrication process for tissue engineering applications. CCECE/CCGEI, Saskatoon, 2005, 1255~1261
23 Iwan Z, Dietmar W. Hutmacher, Kim C. T, Swee H. T. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials, 2003, 24(24):1169~1185
24赵萍,蒋华,周芝庭.熔融沉积快速成形工艺的原理及过程.机械制造与研究, 2003, (5):17~23
25张剑锋,张建华,赵剑锋.激光快速成形制造技术的应用研究进展.航空制造技术, 2002, (7):34~37
26 Tan K. H, Chua C. K, Leong K. F. Scaffold development using selective laser sintering of polyetheretherketone–hydroxyapatite biocomposite blends.Biomaterials, 2003, 24(18):3115~3123
27陈步庆,林柳兰,陆齐,胡庆夕.三维打印技术及系统研究.机电一体化, 2005, 4:13~15
28张爱英,王连才,刘厚利,魏宏亮,冯增国.基于快速成形技术的组织工程支架制备进展.化工进展, 2004, 23(3):267~271
29陈中中,李涤尘,卢秉恒.气压式熔融沉积快速成形系统.电加工与模具, 2002, (2):9~12
30陈中中,早热木,李涤尘,卢秉恒,孙明林.利用快速成形技术制造人工生物活性骨.西安交通大学学报, 2003, 37(3):273~276
31颜永年,崔福斋,张人佶,胡蕴玉.人工骨的快速成形制造.材料导报, 2002, 14(2):11~13
32吴懋亮,周克平.选择性激光烧结方法加工仿生支架的工艺研究。中国制造业信息化, 2006, 36(3):35~38
33郑卫国,颜永年,熊卓.复合材料梯度结构组织工程支架建模方法.材料导报, 2002, 16(11):58~61
34陈立峰,颜永年,郑卫国,熊卓,张人佶.生物材料快速成形设备的设计与实现.设计与研究, 2003, 5:21~23
35 Chua C K, Leong K F, Cheah C M, et al. Development of a tissue engineering scaffold structure library for rapid prototyping. Part 2: Parametric library and assembly program. Advanced Manufacturing Technology, 2003, 21(4): 302~312
36李祥,李涤尘,张彦东,卢秉恒.骨组织微结构观察分析及仿生支架立体光固化间接制造.北京生物医学工程, 2006, 25(2):164~167
37王林,王臻,李祥,李涤尘等.大块组织工程骨支架结构设计制造及与人成骨细胞联合培养观察。中国矫形外科杂志, 2005, 13(5):376~379
38丁焕文,唐春雷,赵中岳等.个体化组织工程支架CAD设计与RP制作的方法的研究.生物骨科材料与临床研究, 2005, 2(1):1~4
39 Starly. B, Lau.W, Bradbury. T, Sun W. Internal architecture design and freeform fabrication of tissue replacement structures. Computer-Aided Design, 2006, 38:115~124
40陈作炳.人工关节CAD/CAM相关理论及其关键技术研究.武汉理工大学博士论文, 2004:63~75
41 Peter X. Ma. Scaffolds for tissue fabrication. Materials Today, 2004, 5:30~40
42毛娅,陈作炳,余新明,绕嵩.基于医学图像的人工骨三维仿生设计.中国体视学与图像分析, 2004, 9(3):160~164
43 Sun W. Binil S, Andrew D and Connie G. Computer-aided tissue engineering: application to biomimetic modeling and design of tissue scaffolds. Biotechnol Appl Chem, 2004, 39:49~58
44李莉敏,郭桂芳,胡庆夕,吴懋亮.面向骨组织工程的三维仿生支架的微观结构研究.中国制造业信息化. 2005, 34(4):86~88
45陈绪兵,叶献方,黄树槐.快速成形领域中的直接切片研究.中国机械工程, 2002, 13(7):71~73
46孙玉文,刘伟军,刘健. CAD/RP系统间数据模型的转换方法与发展.航空精密制造技术, 2001, 37(2):19~22
47李占利.基于STL的快速分层处理软件的研发.西安科技学院学报, 2001, 21(3):263~267