Role of Microstructure in Nanomechanical Behavior of Bone Tissue

微结构在骨组织纳米力学行为中的作用

• 批准号: 7872826
• 负责人: Marjolein C van der Meulen
• 金额: $ 31.03万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7872826
• 关键词: Affect; Behavior; Bone Density; Bone Matrix; Bone Tissue; Collagen; Data; Disease; Dose; Elastic Tissue; Failure; Femur; Fluorides; Fracture; Generations; Goals; Hardness; Heterogeneity; Human; Length; Link; Measurement; Measures; Mechanics; Metabolic acidosis; Microscopy; Minerals; Modeling; Osteoporosis; Performance; Pre-Clinical Model; Property; Rattus; Research Personnel; Role; Science; Sheep; Skeleton; Solid; Specimen; Spectroscopy, Fourier Transform Infrared; Stress; Structure; Techniques; Testing; Time; Tissues; Translating; Vertebral Bone; Vitamin D Deficiency; Weight-Bearing state; base; bisphosphonate; bone; bone geometry; bone mass; bone strength; density; effective therapy; infrared microscopy; lumbar vertebra bone structure; mechanical behavior; mineralization; multi-scale modeling; nanoindentation; nanomechanical; programs; second harmonic; skeletal; submicron

DESCRIPTION (provided by applicant): The role of tissue microstructure in the tissue mechanical properties is important to understanding the determinants of skeletal integrity. The goal of this proposal is to correlate bone tissue composition with tissue mechanical properties for treatments that result in well-established alterations in bone matrix composition and altered whole bone strength to test the following hypotheses: Hypothesis 1: Reduced bone mineral density or increased mineral crystal size reduces tissue elastic modulus and hardness. Specific Aim 1a: Mineral content will be reduced by 3 and 4 weeks of vitamin D-deficiency in growing rats. The treatment will be confirmed with whole bone bending tests. Tissue elastic modulus, composition and microstructure will be characterized. Tissue composition and microstructure will be correlated with indentation moduli and hardness in the femur and lumbar vertebra. Specific Aim 1b: Altered mineralization will be produced by 3 and 4 weeks of fluoride treatment of growing rats to weaken whole bone structure and alter mineral crystal size. Tissue properties will be analyzed and correlated as in Specific Aim 1 a. Hypothesis 2: Metabolic acidosis produces matrix changes that reduce tissue elastic modulus. Specific Aim 2: Metabolic acidosis in sheep is a preclinical model of human osteoporosis that reduces bone mass and alters tissue mineralization. The tissue properties will be analyzed and correlated in this sheep model as in Specific Aim 1. Additionally, bulk properties will be determined for specimens from the cortex. Models incorporating microstructural detail will be used to relate the behavior across length scales. Hypothesis 3: Bisphosphonate treatment increases tissue elastic modulus and hardness. Specific Aim 3: Bisphosphonate treatment will be used to overcome osteoporosis following metabolic acidosis from Specific Aim 2. Tissue and bulk properties will be analyzed and correlated as in Specific Aim 2. We will relate composition and microstructure of bone tissue to the elastic behavior, focusing on the role of mineral and collagen content, crystal size and collagen alignment. Our approach will cross-correlate several microlevel techniques that have not been previously used to characterize bone tissue mechanics.

描述（由申请人提供）：组织微观结构在组织力学性能中的作用对于理解骨骼完整性的决定因素非常重要。本提案的目标是将骨组织组成与组织力学性能相关联，从而导致骨基质组成的明显改变和整个骨强度的改变，以验证以下假设：假设1：骨密度降低或矿物晶体尺寸增加会降低组织弹性模量和硬度。具体目标1a：在生长中的大鼠缺乏维生素d 3和4周后，矿物质含量会降低。治疗将通过整个骨弯曲试验来证实。组织的弹性模量、组成和微观结构将被表征。组织组成和微观结构将与股骨和腰椎的压痕模量和硬度相关。特异性目标1b：对生长中的大鼠进行3和4周的氟化物治疗会产生矿化改变，从而削弱整个骨骼结构并改变矿物晶体大小。组织特性将被分析和关联，具体目标1a。假设2：代谢性酸中毒产生基质变化，降低组织弹性模量。特异性目的2：绵羊代谢性酸中毒是人类骨质疏松症的临床前模型，可减少骨量并改变组织矿化。组织特性将在这个羊模型中进行分析和关联，如在Specific Aim 1中。此外，将确定皮质标本的体积特性。结合微观结构细节的模型将用于关联跨长度尺度的行为。假设3：双膦酸盐处理增加组织弹性模量和硬度。特异性目标3：双膦酸盐治疗将用于克服特异性目标2代谢性酸中毒后的骨质疏松症。组织和体积性质将分析和相关的具体目标2。我们将把骨组织的组成和微观结构与弹性行为联系起来，重点关注矿物质和胶原蛋白含量、晶体大小和胶原蛋白排列的作用。我们的方法将交叉关联以前未用于表征骨组织力学的几种微观水平技术。

项目成果

Simulation of the behaviour of the L1 vertebra for different material properties and loading conditions.

模拟 L1 椎骨在不同材料特性和负载条件下的行为。

• DOI: 10.1080/10255842.2011.636741
• 发表时间: 2013
• 期刊: Computer methods in biomechanics and biomedical engineering
• 影响因子: 1.6
• 作者: Erdem,Ibrahim;Truumees,Eeric;vanderMeulen,MarjoleinCH
• 通讯作者: vanderMeulen,MarjoleinCH

Spatial periodicity in growth plate shear mechanical properties is disrupted by vitamin D deficiency.

维生素 D 缺乏会破坏生长板剪切力学特性的空间周期性。

• DOI: 10.1016/j.jbiomech.2013.04.023
• 发表时间: 2013
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Sevenler,Derin;Buckley,MarkR;Kim,Grace;vanderMeulen,MarjoleinCH;Cohen,Itai;Bonassar,LawrenceJ
• 通讯作者: Bonassar,LawrenceJ

Understanding Bone Strength Is Not Enough.

• DOI: 10.1002/jbmr.3078
• 发表时间: 2017-06
• 期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
• 作者: Hernandez CJ;van der Meulen MC
• 通讯作者: van der Meulen MC