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活骨组织应力与重建适应实验及其生物模型研究

Experimental Study on the Stress and Remodeling Adaptation of Vivo Bone Tissue and Its Biological Model

【作者】 赵文志

【导师】 刘迎曦;

【作者基本信息】 大连理工大学 , 生物医学工程, 2004, 博士

【摘要】 应力与生长是生物力学活的灵魂,功能性适应是生物力学普遍规律。应力与生长关系的研究主要包括两个方面:其中一个方面是从宏观上研究骨生长与重建对其应力环境的适应过程,以期建立一个恰当、准确、实用又能量化的“模型”,使其能够精确表达如何由于功能适应性而形成骨的各种内部组织。另一方面是从微观角度研究应力环境同细胞生长与活力的关系及其力学—生物学转导机制,以期从本质上阐明应力与生长关系的机制。 尽管对骨力学的研究已有上百年的历史,但至今还不能说它已形成一个成熟的分支。把力学原理引进生物体、生物组织与器官是一件非常困难的事,因为生物体的主要特点是有生命,有生命的活组织与无生命的工程材料的结构有根本的区别。 本文从生物力学角度出发,将计算机仿真技术、三维图形重构、计算力学、参数识别反问题等理论、近代医学理论与动物实验相融合,发挥多学科交叉的优势,进行骨骼解剖结构和力学性能与正常功能相适应的研究,并建立活骨组织应力与重建适应生物模型。这种生物建型是在宏观尺度意义下进行的。 论文各章节主要工作概述如下: 第一章主要阐述了生物力学及骨力学的定义,简单介绍了生物力学和骨力学的发展简史、研究特点、研究意义和骨力学的研究方法。接着给出了骨骼生长与重建的基本概念和基本理论。回顾了应力与骨重建理论的发展进程。简要介绍了国内生物力学的发展状况。最后概述了论文的临床背景和研究意义。 第二章首先概述了骨的组织学和生理学,然后建立大鼠动物实验模型,进行3次实验研究,系统研究不同应力环境对大鼠股骨的宏观几何结构、解剖学、组织形态学、骨计量学、骨密度以及股骨生物力学性能的影响,并对应力环境对大鼠股骨生长与重建影响的机理进行了讨论。实验结果发现,活骨组织通过改变其自身的结构、形状、组织成分以及生物力学性能来适应环境。 第三章建立大鼠胫骨骨折模型,从医学和生物力学多角度研究不同的受力状态对动物骨折愈合在组织水平和分子水平的影响;分别在组织学和力学细胞生物学水平探讨了应力与骨重建的机理。研究发现,应力环境影响可间充质细胞的增殖和分化,同时影响胞外基质分子的表达和巨噬细胞的迁入,并改变着参与骨折愈合的细胞间的相互作用。最后进行了长骨内开口效应对其力学性能和应力分布影响的有限元分析,所得结论为临床上骨科手术的实施提供有价值的参考。 第四章是本论文的重点内容。首先详细介绍了活骨组织应力与重建适应生物力学模型的发展现状,然后在动物实验基础上,运用反问题的理论与方法对骨生长与重建方程中的关键参数进行反演识别。再利用正演结合动物实验来验证和修订所建模型。从而得到能够正确反映大鼠骨骼随应力环境变化而进行骨重建的生物力学模型。最后进行大鼠股骨医学CT图像的三维重建。为深入研究生物建模奠定基础。 第五章总结全文,并展望今后的研究方向和研究内容。 本文的研究工作是国家自然科学基金项目(基金号:10472025)、高等学校博士点专项基金项目(基金号2000014107)以及辽宁省科学技术基金项目(基金号:20032109)的一部分。 关键词:动物实验;骨组织:生长与重建;生物模型;反问题;应力环境;有限元方法:生物力学;骨折;CD68;BMP2; 注:本文作者是名临床骨科医生,虽然进入力学专业学习已有3年半的时间,但对于广博的力学知识而言,自己所掌握的可以说只是沧海一粟,九牛一毛,对力学专业的某些名词的理解尚不够深刻。本论文的参考资料有些来自医学、生物医学工程以及生物力学等领域的文献,其中引用的某些术语从纯力学的角度看可能不够准确,如:应力遮挡、应力保护、应力环境等。可见,将交叉学科领域里的名词和术语进行规范和标准化无疑也是我们面临的重要任务之一。希望我的工作能起到抛砖引玉的作用。

【Abstract】 The relationship between stress and growth is alive ghost of biomechanics, functional adaptation is a universal rule of biomechanics. The study of relationship between stress and growth mainly includes two aspects: one is to investigate the adaptation procedure of bone growth and remodeling to its stress environment in order to set up a aptitude, accurate, practical and can be quantified "model", which can precisely express how functional adaptation form the inner tissue of bone; The other is to study the relationship between stress environment and cell growth and energy as well as its mechano-biology transduction mechanism at microcosmic point of view in order to essentially illuminate the mechanism of the connection of stress and growth.Although the biomechanics has been studied for more than one century, but it has not formed a mature embranchment up to the present. It is very difficult to introduce mechanical theory into organism, biological tissue and apparatus, because the main characteristic of organism is that it has "life" there is essential difference between the structure of alive tissue and nonliving engineering material.From biomechanical point of view, this research integrates computer simulation technique, three-dimension image reconstruction, computing mechanics, parameter inversion identification theory and animal experiments. Possessing advantages of multiple subjects crossing, it carries through the investigation of bone anatomical structure and mechanical property adapting to its normal function, and creates stress and remodeling adaptation biological model of living bone tissue. The building of this biological model is carried through under macroscopic scale meaning.The main work of each chapter of the research is summarized in the following:In chapter one, the definitions of biomechanics and bone mechanics aremainly expatiated. The brief history, investigation feature, study meaning ofbiomechanics and bone mechanics are simply introduced. And then, the basic concept and essence theory of bone growth and remodeling are presented. The development course of stress and bone remodeling is reviewed. The development status of biomechanics in our country is briefly introduced. At last, the clinic background and research meaning of the thesis are summarized.In the chapter two, the histology and physiology of bone are firstly summarized, then animal experimental model of rat is built, three experimental studies are put up, the influence of different stress environment on the macroscopic geometrical structure, anatomy, tectology, metrology, bone density and biomechanical property of rat femur is investigated systematically. How the stress environment affects rat femur growth and remodeling is discussed. The experiment result shows that living bone tissue adapts its environment by changing its structure, shape, tissue component and biomechanical property. In chapter three, rat tibia fracture model is created, the influence of stress environment on animal fracture healing at tissue level and molecule level is studied from medical and biomechanical point of view; the mechanism of stress and remodeling is discussed at tissue and mechanocytobiology level respectively. The research shows that stress environment can influence the proliferation and differentiation of mesenchymal cell, at the same time, it also affect the expression of extracellular matrix molecules and the immigration of macrophages, further more change the interaction of cells which participate in fracture healing.At last, a finite element analysis of the effect of open section within a long bone on its mechanical property and stress distribution is carried through, the obtained conclusion provides a valuable reference to clinical orthopaedic operation.The chapter four is the keystone content of the thesis. At first, the development status in quo of living bone tissue stress and remodeling adaptation biomechanical model is particularly introduced, and then, on the basis of animalbiomechanical model is particularly introduced, and then, on the

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