骨组织生长重建的力学生物学机制研究进展

生物力学已被证实是骨组织生长、重建及成形当中一个十分重要的因素. 骨组织的损 伤修复过程本质上是细胞的生物学过程和应力作用下的生长过程. 这虽然肯定了生物力学在 骨组织生长、重建过程中的重要地位, 但是, 人们对生物力学因素如何诱导骨生长、 重建的力学生物学机制仍不甚了解. 而骨组织工程需要更为科学完善的细胞生物学机制来研究和探 索骨组织的构建过程. 本文概述了国内外生物力学与骨组织生长重建的宏微观理论, 主要讨 论了骨组织结构及功能形成过程中的力学生物学相关问题.     

考虑载荷特性的骨重建力学调控机制

骨组织具有适应变化力学环境的能力.通过分析骨组织适应力学环境的调控机制,吸纳工程强度设计准则思想,提出考虑载荷特性的骨重建力学调控机制,探讨载荷特性对力学激励的影响,对牙槽骨“张力区骨增生和压力区骨吸收”的现象进行分析和数值模拟.结果表明考虑载荷特性的骨重建力学调控机制是合理的,是骨重建力学调控机制理论的补充和完善.     

载荷诱导骨生长的力学细胞生物学机制

骨骼的结构和功能在很大程度上依赖于其所处的力学环境,这一观点已被广为接受．自从Ｗｏｌｆｆ提出其著名的骨转换定律以来,骨生长与载荷间的关系一直是生物力学中一个重要的问题．大量的动物实验均证明二者之间存在明确的关联．然而,载荷诱导骨生长的力学细胞生物学（ｍｅｃｈａｎｏｃｙ－ｔｏｂｉｏｌｏｇｙ）机制仍很不清楚．十余年来体外培养骨骼细胞加载的研究为应力（应变）诱导骨生长提供了一个微观理论框架．目前认为,载荷诱导骨生长的过程可分为四个环节,即：力学耦联、生物化学耦联、胞间信号转导和效应细胞反应．详细阐述了这几个环节,并就今后的研究方向作一讨论．     

力敏感受体介导细胞功能调控的力学生物学研究

细胞膜是细胞与外部环境进行物质与能量交换的界面,是调节细胞正常生命活动的重要结构基础.细胞膜上力敏感受体可通过力学作用方式参与并影响细胞的力信号转导等功能.整合素和钙黏素是细胞膜上典型的力敏感受体,可介导细胞与细胞周围基质或邻近细胞发生力学作用,并将力学刺激信号转导为生化信号,进而激活细胞内一系列应答反应,最终影响细胞生长、分化、增殖、凋亡和迁移等功能.力敏感受体介导细胞功能调控研究已成为探索细胞主动响应外界复杂力学微环境的力学生物学机制的关键,为进一步深入认识生理和病理状态下细胞功能变化规律,为揭示疾病的发生、发展机制提供重要的力学生物学理论与实验依据.本文总结了力敏感受体介导细胞功能调控的国内外研究进展;介绍了黏附界面处典型力敏感受体的结构和功能;总结了这些力敏感受体参与的细胞力信号感知与响应的数理模型;概述了细胞通过力敏感受体进行力学信号转导的过程;介绍了黏附介导细胞功能调控的力学生物学过程和机制;简述了体外构建模拟细胞力学微环境中细胞-细胞外基质和细胞-细胞力学相互作用的技术;指出了力敏感受体介导细胞功能调控的力学生物学研究发展趋势和未来方向.     

发育生物学中模式形成的力学模型

对所有多细胞生物体而言,其个体发育均涉及由初始的单个细胞开始,经过在时间和空间上细胞有序地增殖、凋亡、分化、迁移等诸多过程,并最终生成物种特异的生物模式.对模式形成的机制的探讨一直是发育生物学的中心课题.目前已就这个问题积累了大量的分子生物学、生物化学、数学、力学等多学科的研究数据并提出了一些模式形成的理论,然而,迄今为止,模式形成的真正机制仍然很不清楚而需进一步的深入探索.本文简要介绍了生物发育过程中模式形成的一些典型的力学模型,重点在于力学模型的建立及其模型本身的介绍,而对其数值模拟和具体应用很少涉及.      

细胞骨架生物力学进展

细胞骨架力学作为力学细胞生物学的一个新兴领域, 其研究方法突破传统细胞力学思想, 不再把活细胞简化为皮质膜包着的弹性、黏性或黏弹性连续介质体, 而是基于在细胞变形和功能中发挥重要作用的细胞骨架离散网络结构, 在微/纳米尺度建立一种集细胞形态和功能于一体的离散网络结构. 这种细胞骨架模型作为细胞变形和生化事件调控的纽带, 能从分子层次上阐述细胞运动、能量转换、信息传递、基因表达等重大生命活动的潜在机制,同时也能解释生物大分子间相互作用、受体/配体特异性相互作用、大分子自装配、细胞及分子层次的力学-化学耦合, 为定量研究细胞-亚细胞-生物大分子等在多种力学刺激下的响应建立了良好的平台, 对于理解生物模式形成、生物复杂性以及解决重大生物学难题具有深远意义. 本文基于细胞骨架三维离散网络结构特点及其生物学背景, 从生物力学角度详细阐述近几年国际上流行的细胞骨架模型理论分析和研究成果的最新进展.      

骨陷窝-骨细胞形状和方向对骨单元内液体流动行为的影响

骨组织内的流体流动不仅为骨细胞的生存提供了充足营养供应及代谢物排放途径,也在骨重建过程中起到关键作用. 为了更精确地阐明骨内液体流动的具体形式,这项研究利用骨陷窝-骨细胞的密度,形态和方向等参数来计算骨单元内液体的流动行为. 首先,计算出不同形状和方向的骨陷窝周围骨小管的数量及分布情况,其次利用算出的参数以及骨组织其他微结构数据来估计骨组织的渗透率和孔隙率等参数,最后根据计算所得的参数建立骨单元的多孔弹性力学有限元模型,并分析了在轴向位移载荷作用下骨陷窝形状和方向对骨单元内液体渗流行为的影响. 结果表明,在所研究的参数范围内不同骨单元模型的相同区域上,骨陷窝形状影响下的骨单元最大压力和流速比最小的分别增加了86%和18%;骨陷窝方向影响下的最大压力和流速比最小的分别增加了125%和56%. 伸长形骨陷窝对单个骨单元局部压力的影响远大于扁平形和圆形骨陷窝. 骨陷窝从0°绕$x$轴旋转到90°过程中压力是逐渐降低的,且30°,45°和60°的模型对骨单元内局部流速有显著影响. 该模型表示骨陷窝的形状和方向以及骨小管的三维分布对骨单元内液体压力和流速幅值及沿不同方向的流动差异有显著的影响. 这项研究将有助于精确量化描述骨内液体的流体行为.      

骨陷窝--骨细胞形状和方向对骨单元内液体流动行为的影响

骨组织内的流体流动不仅为骨细胞的生存提供了充足营养供应及代谢物排放途径,也在骨重建过程中起到关键作用.为了更精确地阐明骨内液体流动的具体形式,这项研究利用骨陷窝-骨细胞的密度,形态和方向等参数来计算骨单元内液体的流动行为.首先,计算出不同形状和方向的骨陷窝周围骨小管的数量及分布情况,其次利用算出的参数以及骨组织其他微结构数据来估计骨组织的渗透率和孔隙率等参数,最后根据计算所得的参数建立骨单元的多孔弹性力学有限元模型,并分析了在轴向位移载荷作用下骨陷窝形状和方向对骨单元内液体渗流行为的影响.结果表明,在所研究的参数范围内不同骨单元模型的相同区域上,骨陷窝形状影响下的骨单元最大压力和流速比最小的分别增加了86%和18%;骨陷窝方向影响下的最大压力和流速比最小的分别增加了125%和56%.伸长形骨陷窝对单个骨单元局部压力的影响远大于扁平形和圆形骨陷窝.骨陷窝从0°绕x轴旋转到90°过程中压力是逐渐降低的,且30°,45°和60°的模型对骨单元内局部流速有显著影响.该模型表示骨陷窝的形状和方向以及骨小管的三维分布对骨单元内液体压力和流速幅值及沿不同方向的流动差异有显著的影响.这项研究将有助于精确量化描述骨内液体的流体行为.     

Biomechanics of stem cells

干细胞生物力学作为生物力学的重要分支和前沿学科,近年来在力学-生物学、力学-化学耦合等方面取得了重大进展,已成为生物力学乃至生物医学工程最活跃的领域之一,并对发生物学、干细胞生物学、组织修复、再生医学等相关领域产生重要影响.干细胞具有独特的力学性质,可感知、传递、转导和响应生理力学微环境的改变,从而调控干细胞的生长、分化等功能,体现出典型的力学-生物学耦合特征.本文将对干细胞的力学性质与细胞力学模型、在体力学环境对干细胞生长和分化的影响、干细胞对外界力学刺激的响应等方面加以综述.     

干细胞的生物力学研究

干细胞生物力学作为生物力学的重要分支和前沿学科,近年来在力学-生物学、力学-化学耦合等方面取得了重大进展,已成为生物力学乃至生物医学工程最活跃的领域之一,并对发育生物学、干细胞生物学、组织修复、再生医学等相关领域产生重要影响.干细胞具有独特的力学性质,可感知、传递、转导和响应生理力学微环境的改变,从而调控干细胞的生长、分化等功能,体现出典型的力学-生物学耦合特征.本文将对干细胞的力学性质与细胞力学模型、在体力学环境对干细胞生长和分化的影响、干细胞对外界力学刺激的响应等方面加以综述.     

A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper. The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model. Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model), but also predict the realtime development pattern of BMC and BFE, as well as the dynamics of osteoblasts (OBA), osteoclasts (OCA), nitric oxide (NO) and prostaglandin E₂ (PGE₂) for each loading scheme, which can hardly be monitored through experiment. In conclusion, the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass. More importantly, this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated. The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies. Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.     

A theoretical model for surface bone remodeling under electromagnetic loads

A theoretical model for surface bone remodeling under electromagnetic loads is proposed in this paper. In the model, surface bone remodeling is assumed to be related to growth factors. Growth factors in latent form in osteocytes are released to the bone fluid after the osteocytes are absorbed by osteoclasts, and then regulate the bone formation process. At the same time, environmental loadings can influence the generation of growth factors. This paper shows how surface bone remodeling is triggered under the influence of growth factors. Based on this hypothesis, a computational model is established that simulates the bone coupling remodeling process, including internal and surface bone remodeling. The effects of various loadings, including electrical and magnetic loadings, are simulated and compared. The interactions between internal and surface bone remodeling are investigated via the numerical method. The results indicate that an electromagnetic field can strongly influence the bone remodeling process and that the remodeling process will be altered after surface bone remodeling is triggered, compared to the sole effect of the internal remodeling process.     

A predictive mechano-biological model of the bone-implant healing

The quality of the fixation orthopaedic implant to its surrounding bone determines its clinical longevity. Up to 20% of hip replacement operations are currently revisions for aseptic loosening. While this fixation quality is determined primarily by the bone and tissue anchoring the implant, conditions influencing bone growth in the early post-operative period include the surgical technique and coupled mechanical and biochemical factors. The aim of the study was to propose an original mechano-biological formulation of the healing process of periprosthetic tissue. The multiphasic porous model involved the solid osseous matrix, the extracellular fluid phase, the osteoblastic cellular phase responsible from the bone formation and the growth factor phase promoting the cellular activity. To derive the non-linear convective-diffuse governing equations, mass balance was associated to cell active haptotactic and chemotactic migration, growth factor diffusion, cell proliferation (logistic law) and bone formation (reactive medium). The in-vivo application concerned a canine axisymmetric implant which was stable and mechanically unloaded. Predictive numerical results were compared to ex-vivo data from a histologic study. The generic healing pattern involving two main oscillations of the radial bone formation was well predicted. In the future, the model could assist in evaluating the role of growth factor concentrations and their temporal delivering as far as the role of pertinent sources such as bioactive coating or additional biomaterials.     

加载速率对骨的流动电位的影响

骨受力变形时所引起的压力驱动骨内哈佛氏管或骨小管内的液体流动,是骨内出现流动电位的外部原因.由于人体经常受动态载荷作用,研究骨在动态加载过程中流动电位的变化,更有助于了解骨细胞周围电环境的性质.为此,设计了流动电位测试系统,在骨试样两端施加梯形压力波.实验测量了在不同加载速率下流动电位的变化波形.结果显示,加载速率越高,流动电位有减小的趋势.分析认为这是由于微管中局部产生的湍流引起的.     

胞质分裂力学及其分子生物学机制的研究

胞质分裂通过一系列的形态学变化使母细胞一分为二生成两个子细胞,几乎整个胞质分裂过程都伴随着力学现象.形成刚度或黏弹性互不相同的区域对细胞形态的改变至关重要,特殊肌动蛋白与交联蛋白是导致细胞局部刚度改变的重要因素.因此有必要深入理解细胞如何变形、以及促进细胞变形的材料特性及其分子生物学基础.本文将针对细胞的力学特性、胞质分裂中的力学现象以及分子生物学基础进行讨论.      

Numerical simulation on the adaptation of forms in trabecular bone to mechanical disuse and basic multi-cellular unit activation threshold at menopause

The objective of this paper is to identify the effects of mechanical disuse and basic multi-cellular unit （BMU） activation threshold on the form of trabecular bone during menopause. A bone adaptation model with mechanical- biological factors at BMU level was integrated with finite element analysis to simulate the changes of trabecular bone structure during menopause. Mechanical disuse and changes in the BMU activation threshold were applied to the model for the period from 4 years before to 4 years after menopause. The changes in bone volume fraction, trabecular thickness and fractal dimension of the trabecular structures were used to quantify the changes of trabecular bone in three different cases associated with mechanical disuse and BMU activation threshold. It was found that the changes in the simulated bone volume fraction were highly correlated and consistent with clinical data, and that the trabecular thickness reduced signi-ficantly during menopause and was highly linearly correlated with the bone volume fraction, and that the change trend of fractal dimension of the simulated trabecular structure was in correspondence with clinical observations. The numerical simulation in this paper may help to better understand the relationship between the bone morphology and the mecha-nical, as well as biological environment; and can provide a quantitative computational model and methodology for the numerical simulation of the bone structural morphological changes caused by the mechanical environment, and/or the biological environment.