面向骨组织工程的仿生支架建模研究

发布时间：2018-10-08 08:03

【摘要】：由于疾病、事故等原因所造成的大面积骨缺损,已经成为了临床医学治疗的重要难题之一。近年来,随着骨组织工程技术的迅速发展,利用种子细胞与仿生支架的复合体构建组织工程化骨,作为修复缺损骨的移植材料,已经成为骨缺损修复的一种全新的治疗模式,也成为了骨组织工程领域的研究热点。在组织工程化骨的构建中,仿生支架能够为新生的骨组织提供合适的生长空间和足够的机械支撑,并能够介导细胞间的信号传递和相互作用,诱导新骨的形成。因此,仿生支架的制备成为骨组织工程研究的关键,具有极为重要的研究价值。仿生支架的制备包括解剖外形的制造和内部微观孔的构建。传统的制备方法更多地致力于内部微观孔的构建,解剖外形主要依靠手工成型或模具成型,制造精度相当低。而且,支架内部结构性能无法在制造前进行评价,孔隙率、连通性等参数在制造过程中也难以控制。随着快速成形技术在骨组织工程领域应用的不断深入,使得利用快速成形方法制备仿生支架成为一种更为理想的途径。采用快速成形技术,不仅可以一次成型出精确的支架解剖外形和复杂的内部微观孔结构,而且可以根据支架的三维模型进行内部结构性能的加工前评价,从而制造出性能优良、结构合理的仿生支架。因此,仿生支架建模是利用快速成形方法制备仿生支架的一项关键技术。正是基于上述的研究背景和应用需求,本文以仿生支架为研究对象,面向骨组织工程领域展开了仿生支架的外观模型和内部结构模型的构建,以及支架内部结构性能评价等方面的研究工作。主要的研究内容及成果包括以下几个方面: (1)基于Delaunay三角剖分算法思想,提出了缺损骨曲面模型的重建方法。根据CT图像数据构建像素立方体,通过骨组织图像的灰度阈值的比较,实现空间点云数据的采集。运用K-近邻求解和二维Delannay近邻算法,简化了空间点集的Delannay三角化过程,加速了曲面重建的效率。利用局部可变球映射算法解决了孔洞特征拓扑重构的问题,从而获得精确的缺损骨曲面模型。同时,重构的曲面模型为仿生支架的解剖外形以及内部微观孔结构的构建,提供了良好的数字模型。 (2)在分析骨缺损的病理特征和种类的基础上,提出了面向骨缺损修复的仿生支架外观模型的构建方法。该方法采用二面角判别算法自动搜索孔洞的边界,获取孔洞边界边所构成的三维多边形;基于面积最小原理进行多边形的三角剖分,根据边长最短原则进行网格细化,实现三维多边形的Delaunay三角剖分;利用加权伞算子控制修补曲面的曲率变化,进行曲面网格的光顺处理,保证修补曲面片与周围曲面的光滑过渡。通过各模型之间的布尔运算构建仿生支架的外观模型,大大地降低建模的复杂度。 (3)采用多约束背包问题模型与混合遗传算法综合的方法来构建仿生支架的内部微观孔结构模型。基于多约束背包问题模型,采用椭球体作为单元体,构建支架内部微观孔结构的负模型,利用混合遗传算法进行求解。在遗传算子设计中,采用比例选择与最优保存策略相结合的混合选择算子,提高算法的运行效率和收敛性;采用均匀交叉算子避免种群多样性的退化,使得微观孔结构呈多样性;采用均匀变异算子增强算法的局部搜索能力,促进群体的多样性演化;采用扰动算子对解空间进行局部调整,提高算法的全局搜索能力。然后,通过支架的外观模型与负模型之间的布尔运算,获得含微观孔的仿生支架模型。 (4)分析了影响仿生支架内部结构性能的因素,建立了支架微观孔结构性能的评价指标体系,包括孔隙率、连通性、均匀性、扭曲度和比表面积五项评价指标。基于支架微观孔结构的负模型,提出了各项评价指标值的计算方法。分析了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,基于AHP方法确定了各项评价指标在支架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,提出了仿生支架内部结构性能的综合评价模型,并通过计算各项评价指标的灰色关联度来综合评判支架内部结构性能的优劣。 (5)根据上述的理论和方法,采用面向对象技术和可视化技术开发了仿生支架建模的原型系统,初步实现了缺损骨曲面模型的三维重建、修复体模型的构建、支架内部结构建模及性能评价等功能,验证了所提出的建模方法的科学性、合理性和正确性。
[Abstract]:Due to the large-area bone defect caused by diseases and accidents, it has become one of the important problems in clinical medicine treatment. In recent years, with the rapid development of bone tissue engineering technology, tissue-engineered bone is constructed by using a complex of seed cells and a bionic scaffold, It has become a hot topic in the field of bone tissue engineering. In the construction of tissue engineered bone, the bionic scaffold can provide suitable growth space and adequate mechanical support for the new bone tissue, and can mediate signaling and interaction between cells, and induce the formation of new bone. Therefore, the preparation of bionic scaffold is the key to the research of bone tissue engineering, and it has extremely important research value. Preparation of bionic scaffolds including the manufacture of anatomical shapes and internal microscopic pores The traditional preparation method is more focused on the construction of the internal micro-hole, in addition, that performance of the internal structure of the stent can not be evaluated before manufacture, and the parameters such as porosity, connectivity and the like are difficult to With the development of rapid prototyping technology in the field of bone tissue engineering, the preparation of bionic scaffold by rapid prototyping is an ideal method. By adopting the rapid forming technology, the accurate stent anatomical shape and the complex internal micro-hole structure can be molded at one time, and the pre-processing evaluation of the internal structure performance can be performed according to the three-dimensional model of the bracket, so that the bionic robot has the advantages of excellent performance and reasonable structure. As a result, the modeling of bionic scaffold is a key to the preparation of bionic scaffold by rapid prototyping Based on the above research background and application requirements, this paper takes the bionic scaffold as the research object, develops the appearance model of bionic scaffold and the construction of internal structure model in the field of bone tissue engineering, and evaluates the internal structure performance of the scaffold. Research work. The main research contents and achievements include: The following aspects: (1) Based on Delaunay triangulation algorithm, the defect bone curve is put forward. According to the CT image data, the pixel cube is constructed, the gray threshold value of the bone tissue image is compared, The Delannay triangulation process of the spatial point set is simplified by using the K-nearest neighbor algorithm and the two-dimensional Delannay nearest neighbor algorithm. The efficiency of surface reconstruction is improved. Using local variable sphere mapping algorithm, the problem of hole feature topological reconstruction is solved, so it is accurate. At the same time, the reconstructed curved surface model is the anatomical shape of the bionic scaffold and the construction of the internal micro-hole structure. A good digital model is presented. (2) On the basis of analyzing the pathological characteristics and kinds of bone defects, we put forward the bionic repair of bone defect. The method comprises the following steps of: automatically searching the boundary of the hole by using a two-face angle discrimination algorithm to obtain a three-dimensional polygon formed by the edge of the hole; carrying out the triangular section of the polygon based on the minimum principle of the area; carrying out mesh refinement according to the shortest principle of the side length to realize the D of the three-dimensional polygon; elaunay triangulation; using a weighted umbrella operator to control the curvature change of the repaired surface, performing fairing processing on the curved surface grid, and ensuring the repaired surface the appearance model of the bionic support is constructed by Boolean operation between the models, and the complexity of modeling is greatly reduced. (3) a multi-constraint knapsack problem model and a hybrid genetic algorithm are adopted to construct the multi-constraint knapsack problem model and the hybrid genetic algorithm, The invention relates to an internal micro-hole structure model of a bionic bracket, which adopts an ellipsoid as a unit body based on a multi-constraint knapsack problem model, and constructs a negative mode of the micro-hole structure inside the bracket. The hybrid genetic algorithm is used to solve the problem. In the genetic operator design, the hybrid selection operator combined with the optimal preservation strategy is adopted to improve the operation efficiency and the convergence of the algorithm, and the uniform crossover operator is adopted to avoid the diversity of the population. The local search ability of the algorithm is enhanced by the uniform mutation operator, and the diversity evolution of the population is promoted; the solution space is local by using the perturbation operator. Adjust and improve the global search capability of the algorithm. Then, the Boolean operation between the appearance model of the stent and the negative model (4) analyzing the factors influencing the internal structure performance of the bionic bracket, establishing an evaluation index system for the structure performance of the micro-hole of the bracket, Five evaluation indexes of uniformity, twist and specific surface area. The influence degree of various evaluation indexes on the biological activity, mechanical strength and degradation speed of the scaffold was analyzed, and the evaluation index was determined based on the AHP method. Based on the evaluation theory of grey relational grade analysis, a comprehensive evaluation model of the internal structure performance of bionic scaffold was put forward, and the grey relation of each evaluation index was calculated. Based on the theory and method described above, the prototype system of bionic scaffold was developed by using object-oriented technology and visualization technique. The function of constructing, modeling and evaluating the internal structure of the bracket, and the like are verified.
【学位授予单位】：上海大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R329;TP391.41;O242.1

【参考文献】