【摘要】：由于疾病、事故等原因所造成的大面積骨缺損,已經(jīng)成為了臨床醫(yī)學(xué)治療的重要難題之一。近年來(lái),隨著骨組織工程技術(shù)的迅速發(fā)展,利用種子細(xì)胞與仿生支架的復(fù)合體構(gòu)建組織工程化骨,作為修復(fù)缺損骨的移植材料,已經(jīng)成為骨缺損修復(fù)的一種全新的治療模式,也成為了骨組織工程領(lǐng)域的研究熱點(diǎn)。在組織工程化骨的構(gòu)建中,仿生支架能夠?yàn)樾律墓墙M織提供合適的生長(zhǎng)空間和足夠的機(jī)械支撐,并能夠介導(dǎo)細(xì)胞間的信號(hào)傳遞和相互作用,誘導(dǎo)新骨的形成。因此,仿生支架的制備成為骨組織工程研究的關(guān)鍵,具有極為重要的研究?jī)r(jià)值。 仿生支架的制備包括解剖外形的制造和內(nèi)部微觀孔的構(gòu)建。傳統(tǒng)的制備方法更多地致力于內(nèi)部微觀孔的構(gòu)建,解剖外形主要依靠手工成型或模具成型,制造精度相當(dāng)?shù)�。而�?支架內(nèi)部結(jié)構(gòu)性能無(wú)法在制造前進(jìn)行評(píng)價(jià),孔隙率、連通性等參數(shù)在制造過(guò)程中也難以控制。隨著快速成形技術(shù)在骨組織工程領(lǐng)域應(yīng)用的不斷深入,使得利用快速成形方法制備仿生支架成為一種更為理想的途徑。采用快速成形技術(shù),不僅可以一次成型出精確的支架解剖外形和復(fù)雜的內(nèi)部微觀孔結(jié)構(gòu),而且可以根據(jù)支架的三維模型進(jìn)行內(nèi)部結(jié)構(gòu)性能的加工前評(píng)價(jià),從而制造出性能優(yōu)良、結(jié)構(gòu)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備仿生支架的一項(xiàng)關(guān)鍵技術(shù)。 正是基于上述的研究背景和應(yīng)用需求,本文以仿生支架為研究對(duì)象,面向骨組織工程領(lǐng)域展開(kāi)了仿生支架的外觀模型和內(nèi)部結(jié)構(gòu)模型的構(gòu)建,以及支架內(nèi)部結(jié)構(gòu)性能評(píng)價(jià)等方面的研究工作。主要的研究?jī)?nèi)容及成果包括以下幾個(gè)方面: (1)基于Delaunay三角剖分算法思想,提出了缺損骨曲面模型的重建方法。根據(jù)CT圖像數(shù)據(jù)構(gòu)建像素立方體,通過(guò)骨組織圖像的灰度閾值的比較,實(shí)現(xiàn)空間點(diǎn)云數(shù)據(jù)的采集。運(yùn)用K-近鄰求解和二維Delannay近鄰算法,簡(jiǎn)化了空間點(diǎn)集的Delannay三角化過(guò)程,加速了曲面重建的效率。利用局部可變球映射算法解決了孔洞特征拓?fù)渲貥?gòu)的問(wèn)題,從而獲得精確的缺損骨曲面模型。同時(shí),重構(gòu)的曲面模型為仿生支架的解剖外形以及內(nèi)部微觀孔結(jié)構(gòu)的構(gòu)建,提供了良好的數(shù)字模型。 (2)在分析骨缺損的病理特征和種類的基礎(chǔ)上,提出了面向骨缺損修復(fù)的仿生支架外觀模型的構(gòu)建方法。該方法采用二面角判別算法自動(dòng)搜索孔洞的邊界,獲取孔洞邊界邊所構(gòu)成的三維多邊形;基于面積最小原理進(jìn)行多邊形的三角剖分,根據(jù)邊長(zhǎng)最短原則進(jìn)行網(wǎng)格細(xì)化,實(shí)現(xiàn)三維多邊形的Delaunay三角剖分;利用加權(quán)傘算子控制修補(bǔ)曲面的曲率變化,進(jìn)行曲面網(wǎng)格的光順處理,保證修補(bǔ)曲面片與周圍曲面的光滑過(guò)渡。通過(guò)各模型之間的布爾運(yùn)算構(gòu)建仿生支架的外觀模型,大大地降低建模的復(fù)雜度。 (3)采用多約束背包問(wèn)題模型與混合遺傳算法綜合的方法來(lái)構(gòu)建仿生支架的內(nèi)部微觀孔結(jié)構(gòu)模型。基于多約束背包問(wèn)題模型,采用橢球體作為單元體,構(gòu)建支架內(nèi)部微觀孔結(jié)構(gòu)的負(fù)模型,利用混合遺傳算法進(jìn)行求解。在遺傳算子設(shè)計(jì)中,采用比例選擇與最優(yōu)保存策略相結(jié)合的混合選擇算子,提高算法的運(yùn)行效率和收斂性;采用均勻交叉算子避免種群多樣性的退化,使得微觀孔結(jié)構(gòu)呈多樣性;采用均勻變異算子增強(qiáng)算法的局部搜索能力,促進(jìn)群體的多樣性演化;采用擾動(dòng)算子對(duì)解空間進(jìn)行局部調(diào)整,提高算法的全局搜索能力。然后,通過(guò)支架的外觀模型與負(fù)模型之間的布爾運(yùn)算,獲得含微觀孔的仿生支架模型。 (4)分析了影響仿生支架內(nèi)部結(jié)構(gòu)性能的因素,建立了支架微觀孔結(jié)構(gòu)性能的評(píng)價(jià)指標(biāo)體系,包括孔隙率、連通性、均勻性、扭曲度和比表面積五項(xiàng)評(píng)價(jià)指標(biāo)。基于支架微觀孔結(jié)構(gòu)的負(fù)模型,提出了各項(xiàng)評(píng)價(jià)指標(biāo)值的計(jì)算方法。分析了各項(xiàng)評(píng)價(jià)指標(biāo)對(duì)支架的生物活性、力學(xué)強(qiáng)度、降解速度等性能的影響程度,基于AHP方法確定了各項(xiàng)評(píng)價(jià)指標(biāo)在支架結(jié)構(gòu)性能綜合評(píng)價(jià)中的權(quán)重值�；诨疑P(guān)聯(lián)度分析的評(píng)價(jià)理論,提出了仿生支架內(nèi)部結(jié)構(gòu)性能的綜合評(píng)價(jià)模型,并通過(guò)計(jì)算各項(xiàng)評(píng)價(jià)指標(biāo)的灰色關(guān)聯(lián)度來(lái)綜合評(píng)判支架內(nèi)部結(jié)構(gòu)性能的優(yōu)劣。 (5)根據(jù)上述的理論和方法,采用面向?qū)ο蠹夹g(shù)和可視化技術(shù)開(kāi)發(fā)了仿生支架建模的原型系統(tǒng),初步實(shí)現(xiàn)了缺損骨曲面模型的三維重建、修復(fù)體模型的構(gòu)建、支架內(nèi)部結(jié)構(gòu)建模及性能評(píng)價(jià)等功能,驗(yàn)證了所提出的建模方法的科學(xué)性、合理性和正確性。
[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.
【學(xué)位授予單位】：上海大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2011
【分類號(hào)】：R329;TP391.41;O242.1

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