青光眼发病机理——筛板变形研究进展

青光眼是世界上第一大不可逆致盲眼病.其病变与眼内压直接相关,控制眼内压是目前控制青光眼发展的唯一有效途径,但发病的确切机制尚未明确.现已证实,青光眼的原发部位是巩膜筛板:由筛板前后分别承受的眼内压与颅内压产生的压力差会导致筛板结构与形态发生变化,进而挤压穿过筛板的视觉神经,造成视觉神经损伤,产生不可逆的视觉损失.因此,青光眼的发病机理与筛板的力学特性及其周围的力学环境密切相关.自从筛板被确定为青光眼视神经损害的原发部位,筛板便成为该领域的研究热点.其中,通过建立筛板力学模型,研究眼内压与颅内压作用下筛板的受力变形,进而分析筛板变形对视神经的损伤,有助于揭示青光眼视神经损伤机制及青光眼的发病机理.本文将从相关实验、理论和计算以及临床等方面介绍青光眼发病机理中筛板变形的研究进展以及目前存在的问题.      

Multi-scale Modeling of Vision-Guided Remodeling and Age-Dependent Growth of the Tree Shrew Sclera During Eye Development and Lens-Induced Myopia

The sclera uses unknown mechanisms to match the eye’s axial length to its optics during development, producing eyes with good focus (emmetropia). A myopic eye is too long for its own optics. We propose a multi-scale computational model to simulate eye development based on the assumption that scleral growth is controlled by genetic factors while scleral remodeling is driven by genetic factors and the eye’s refractive error. We define growth as a mechanism that changes the tissue volume and mass while remodeling involves internal micro-deformations that are volume-preserving at the macro-scale. The model was fitted against longitudinal refractive measurements in tree shrews of different ages and exposed to three different visual conditions: (i) normal development; (ii) negative lens wear to induce myopia; and (iii) recovery from myopia by removing the negative lens. The model was able to replicate the age- and vision-dependent response of the tree shrew experiments. Scleral growth ceased at younger age than scleral remodeling. The remodeling rate decreased as the eye emmetropized but increased at any age when a negative lens was put on. The predictive power of the model was investigated by calculating the susceptibility to scleral remodeling and the response to form deprivation myopia in tree shrews. Both predictions were in good agreement with experimental data that were not used to fit the model. We propose the first model that distinguishes scleral growth from remodeling. The good agreement of our results with experimental data supports the notion that scleral growth and scleral remodeling are two independently controlled mechanisms during eye development.     

眼固体生物力学研究

眼是光转换的视觉器官, 通常考虑将其作为一个生物力学结构. 眼睛是眼内肌和眼外肌产生压力的系统, 具有复杂的内血管系统,产生流体和溶合物的传导系统. 从生物力学角度看, 眼存在固体生物力学、流体生物力学和生物传输等问题. 本综述中, 介绍眼睛有意义的生物固体力学各方面研究成果及尚待解决的问题, 其研究对象为巩膜、角巩膜、角膜、视网膜、筛板以及眼调节和老花. 回顾测量巩膜力学性质和角巩膜应力－应变性质模型的有关研究成果, 然后论述这些研究成果的应用.巩膜力学另一重要应用是对近视的了解, 即眼的轴长过长使长距离光线不能够清晰聚焦于视网膜而引起近视. 角膜生物力学一个显著的应用是预测激光切开剖面手术, 它将使屈光角膜手术达到最优的术后视敏度. 筛板是眼中最具有生物力学研究兴趣的组织之一, 它是跨过巩膜管的多孔的结缔组织. 推导出青光眼的视神经病的力学理论.证据表明围绕着睫状肌的结蹄组织发生变化可能妨碍它的自由收缩的能力, 因此老花的病理学原因可能是多因素的.      

A modified relation between the intraocular and intracranial pressures

A modified relation between the intraocular and intracranial pressures is presented by employing the least square method to fit the existing experiments. Relative analysis here indicates that this modified relation not only is better than the previous relation by comparing with the existing experimental data but also overcomes the induced singularity in applying the existing mechanical models to compute the mechanical properties of the lamina cribrosa. The present study will be a beneficial help to understanding the relationship between the intraocular and intracranial pressures and even glaucomatous developing.     

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.     

Modeling of growth and remodeling in soft biological tissues with multiple constituents

Among the various important characteristics of biological tissues is their ability to grow and remodel. It is well-known that one of the primary triggers behind the growth and remodeling process is changes in the mechanical environment, for instance changes in stress, strain, etc. These mechanisms of mechanotransduction are the driving force behind many changes in structure and function including growth and remodeling. The purpose of this article is to formulate better constitutive equations for the stress in tissues with multiple constituents undergoing growth and remodeling. This is a very complex problem and is of tremendous importance. Here, we do the modeling from a mechanics point of view, utilizing the theory of natural configurations coupled with population dynamics to accurately model the production and removal of the different constituents that comprise the tissue. This is accomplished by deriving a generalized McKendrick equation for growth and remodeling and has the advantage of directly including the age distribution of constituents into the model. The population distribution function is then used to determine the stress in the tissue.     

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.     

An experimental and analytical treatment of matrix cracking in cross-ply laminates

The development of damage in cross-ply Hercules AS4/3502 graphite/epoxy laminates has been investigated. Specific endeavors were to identify the mechanisms for initiation and growth of matrix cracks and to determine the effect of matrix cracking on the stiffness loss in cross-ply laminates. Two types of matrix cracks were identified. These include both straight and curved cracks. The experimental study of matrix crack damage revealed that the curved cracks formed after the straight cracks and followed a repeatable pattern of location and orientation relative to the straight cracks. Therefore, it was postulated that the growth mechanism for curved cracks is driven by the stress state resulting from the formation of the straight cracks. This phenomenon was analytically investigated by a finite-element model of straight cracks in a cross-ply laminate. The finite-element results provide supporting evidence for the postulated growth mechanism. The experimental study also revealed that the number of curved cracks increased with the number of consecutive 90-deg plies. Finally, experimental results show as much as 10-percent degradation in axial stiffness due to matrix cracking in cross-ply graphite/epoxy laminates.     

Constrained mixture models as tools for testing competing hypotheses in arterial biomechanics: A brief survey

Hypothesis testing via numerical models has emerged as a powerful tool which permits the verification of theoretical frameworks against canonical experimental and clinical observations. Cleverly designed computational experiments also inspire new methodologies by elucidating important biological processes and restricting parametric spaces. Constrained mixture models of arterial growth and remodeling (G&R) can facilitate the design of computational experiments which can bypass technical limitations in the laboratory, by considering illustrative special cases. The resulting data may then inform the design of focused experimental techniques and the development of improved theories. This work is a survey of computational hypothesis-testing studies, which exploit the unique abilities offered by the constrained mixture theory of arterial G&R. Specifically, we explore the core hypotheses integrated in these models, review their basic mathematical conceptualizations, and recapitulate their most salient and illuminating findings. We then assess how a decade's worth of constrained mixture models have contributed to a lucid, emerging picture of G&R mechanisms.     

Modeling Heart Development

Mechanics plays a major role in heart development. This paper reviews some of the mechanical aspects involved in theoretical modeling of the embryonic heart as it transforms from a single tube into a four-chambered pump. In particular, large deformations and significant alterations in structure lead to highly nonlinear boundary value problems. First, the biological background for the problem is discussed. Next, a modified elasticity theory is presented that includes active contraction and growth, and the theory is incorporated into a finite element analysis. Finally, models for the heart are presented to illustrate the developmental processes of growth, remodeling, and morphogenesis. Combining such models with appropriate experiments should shed light on the complex mechanisms involved in cardiac development. This revised version was published online in July 2006 with corrections to the Cover Date.     

Surface remodeling of bones induced by intra-medullary nailing

The paper is devoted to a study on the surface remodeling of bones. Anisotropy and piezoelectricity of bone tissue (as per previous experimental studies) are incorporated in the analysis. Surface remodeling induced by intra-medullary nailing is of primary concern in the study.     

The influence of different loads on the remodeling process of a bone and bioresorbable material mixture with voids

A model of a mixture of bone tissue and bioresorbable material with voids was used to numerically analyze the physiological balance between the processes of bone growth and resorption and artificial material resorption in a plate-like sample. The adopted model was derived from a theory for the behavior of porous solids in which the matrix material is linearly elastic and the interstices are void of material. The specimen—constituted by a region of bone living tissue and one of bioresorbable material—was acted by different in-plane loading conditions, namely pure bending and shear. Ranges of load magnitudes were identified within which physiological states become possible. Furthermore, the consequences of applying different loading conditions are examined at the end of the remodeling process. In particular, maximum value of bone and material mass densities, and extensions of the zones where bone is reconstructed were identified and compared in the two different load conditions. From the practical view point, during surgery planning and later rehabilitation, some choice of the following parameters is given: porosity of the graft, material characteristics of the graft, and adjustment of initial mixture tissue/bioresorbable material and later, during healing and remodeling, optimal loading conditions.     

基于近场动力学理论的单层板损伤分析方法

基于键基近场动力学理论（PD）构建复合材料的单层板模型,在本构方程中引入连续变化的键刚度,以表示复合材料中与纤维夹角相关的力学性能的变化。推导了与复合材料主方向热膨胀系数相关的任意方向的热膨胀系数,为热载荷的施加提供理论支持,将热载荷和力学载荷统一于本构方程中。最后,对预先存在裂纹的单层板进行裂纹扩展模式的仿真,得到预期的仿真结果,并与已有实验结果对比验证模型的有效性。     

Growth,mass transfer,and remodeling in fiber-reinforced,multi-constituent materials

We represent a biological tissue by a multi-constituent, fiber-reinforced material, in which we consider two phases: fluid, and a fiber-reinforced solid. Among the various processes that may occur in such a system, we study growth, mass transfer, and remodeling. To us, mass transfer is the reciprocal exchange of constituents between the phases, growth is the variation of mass of the system in response to interactions with the surrounding environment, and remodeling is the evolution of its internal structure. We embrace the theory according to which these events, which lead to a structural reorganization of the system and anelastic deformations, require the introduction of balance laws, which complete the physical picture offered by the standard ones. The former are said to be non-standard. Our purposes are to determine the rates of anelastic deformation related to mass transfer and growth, and to study fiber reorientation in the case of a statistical distribution of fibers. In particular, we discuss the use of the non-standard balance laws in modeling transfer of mass, and compare our results with a formulation in which such balance laws are not introduced.     

Prediction of progressive failure in multidirectional composite laminated panels

A mechanism-based progressive failure analyses (PFA) approach is developed for fiber reinforced composite laminates. Each ply of the laminate is modeled as a nonlinear elastic degrading lamina in a state of plane stress according to Schapery theory (ST). In this theory, each lamina degrades as characterized through laboratory scale experiments. In the fiber direction, elastic behavior prevails, however, in the present work, the phenomenon of fiber microbuckling, which is responsible for the sudden degradation of the axial lamina properties under compression, is explicitly accounted for by allowing the fiber rotation at a material point to be a variable in the problem. The latter is motivated by experimental and numerical simulations that show that local fiber rotations in conjunction with a continuously degrading matrix are responsible for the onset of fiber microbuckling leading to kink banding. These features are built into a user defined material subroutine that is implemented through the commercial finite element (FE) software ABAQUS in conjunction with classical lamination theory (CLT) that considers a laminate as a collection of perfectly bonded lamina (Herakovich, C.T., 1998. Mechanics of Fibrous Composites. Wiley, New York). The present model, thus, disbands the notion of a fixed compressive strength, and instead uses the mechanics of the failure process to provide the in situ compression strength of a material point in a lamina, the latter being dictated strongly by the current local stress state, the current state of the lamina transverse material properties and the local fiber rotation. The inputs to the present work are laboratory scale, coupon level test data that provide information on the lamina transverse property degradation (i.e. appropriate, measured, strain–stress relations of the lamina transverse properties), the elastic lamina orthotropic properties, the ultimate tensile strength of the lamina in the fiber direction, the stacking sequence of the laminate and the geometry of the structural panel. The validity of the approach advocated is demonstrated through numerical simulations of the response of two composite structural panels that are loaded to complete failure. A flat, 24-ply unstiffened panel with a cutout subjected to in-plane shear loading, and a double notched 70-ply unstiffened stitched panel subjected to axial compression are selected for study. The predictions of the simulations are compared against experimental data. Good agreement between the present PFA and the experimental data are reported.     

PREDICTIVE APPROACH TO FAILURE OF COMPOSITE LAMINATES WITH EQUIVALENT CONSTRAINT MODEL

<正>This work established a new analytical model based upon the equivalent constraint model(ECM)to constitute an available predictive approach for analyzing the ultimate strength and simulating the stress/strain response of general symmetric laminates subjected to combined loading,by taking into account the effect of matrix cracking.The ECM was adopted to mainly predict the in-plane stiffness reduction of the damaged laminate.Basic consideration that progressive matrix cracking provokes a re-distribution of the stress fields on each lamina within laminates, which greatly deteriorates the stress distributed in the primary load-bearing lamina and leads to the final failure of the laminates,is introduced for the construction of the failure criterion. The effects of lamina properties,lay-up configurations and loading conditions on the behaviors of the laminates were examined in this paper.A comparison of numerical results obtained from the established model and other existed models and published experimental data was presented for different material systems.The theory predictions demonstrated great match with the experimental observations investigated in this study.     

Measurement of Mechanical Properties of Soft Tissues In Vitro Under Controlled Tissue Hydration

Alterations in tissue hydration that accompany inflammation or chronic remodeling of the Extracellular Matrix (ECM) have significant impact on the biomechanics of vascular tissue in health and disease. Examination of tissue behavior under controlled hydration in vitro could be helpful in better understanding the effects of tissue water content on its mechanical properties where in vivo tissue conditioning could not be possible. This study explains a multistage experimental protocol that allows both to prepare the tissue specimens with specific water content and to measure their mechanical behavior while maintaining the water content constant during the laboratory experimentation. Stress relaxation behaviors of the bovine aortic specimens–extracted from native, collagen-denatured and elastin-isolated tissues–were obtained within a water content range of 100–400 %. Using this method, distinct relaxation behaviors were obtained from tissue specimens with changing ECM treatments and hydration levels. The relaxation behavior was found to conform to a 4-parameter linear-viscoelastic macromechanical model consisting of two Maxwell components in parallel. The macromechanical model was able to distinguish between the morphological mechanisms associated with ECM elastin and collagen.     

Left Ventricular Geometry,Tissue Composition,and Residual Stress in High Fat Diet Dahl-Salt Sensitive Rats

Background

Hypertension drives myocardial remodeling, leading to changes in structure, composition and mechanical behavior, including residual stress, which are linked to heart disease progression in a gender-specific manner. Emerging therapies are also targeting constituent-specific pathological features. All previous studies, however, have characterized remodeling in the intact tissue, rather than isolated tissue constituents, and did not include sex as a biological variable.

Objective

In this study we first identified the contribution of collagen fiber network and myocytes to the myocardial residual stress/strain in Dahl-Salt sensitive rats fed with high fat diet. Then, we quantified the effect of hypertension on the remodeling of the left ventricle (LV), as well as the existence of sex-specific remodeling features.

Methods

We performed mechanical tests (opening angle, ring-test) and histological analysis on isolated constituents and intact tissue of the LV. Based on the measurements from the tests, we performed a stress analysis to evaluate the residual stress distribution. Statistical analysis was performed to identify the effects of constituent isolation, elevated blood pressure, and sex of the animal on the experimental measurements and modeling results.

Results

Hypertension leads to reduced residual stress/strain in the intact tissue, isolated collagen fibers, and isolated myocytes in male and female rats. Collagen remains the largest contributor to myocardial residual stress in both normotensive and hypertensive animals. We identified sex-differences in both hypertensive and normotensive animals.

Conclusions

We observed both constituent- and sex-specific remodeling features in the LV of an animal model of hypertension.

     

Growth and remodeling of load-bearing biological soft tissues

The past two decades reveal a growing role of continuum biomechanics in understanding homeostasis, adaptation, and disease progression in soft tissues. In this paper, we briefly review the two primary theoretical approaches for describing mechano-regulated soft tissue growth and remodeling on the continuum level as well as hybrid approaches that attempt to combine the advantages of these two approaches while avoiding their disadvantages. We also discuss emerging concepts, including that of mechanobiological stability. Moreover, to motivate and put into context the different theoretical approaches, we briefly review findings from mechanobiology that show the importance of mass turnover and the prestressing of both extant and new extracellular matrix in most cases of growth and remodeling. For illustrative purposes, these concepts and findings are discussed, in large part, within the context of two load-bearing, collagen dominated soft tissues—tendons/ligaments and blood vessels. We conclude by emphasizing further examples, needs, and opportunities in this exciting field of modeling soft tissues.