Role of Microstructure in Nanomechanical Behavior of Bone Tissue

描述(由申请人提供)：组织微结构在组织机械性能中的作用对于理解骨骼完整性的决定因素很重要。这项建议的目标是将骨组织成分与组织机械性能联系起来，用于治疗导致公认的骨基质成分改变和改变整体骨强度的治疗，以检验以下假设：假设1：骨密度减少或矿物晶体尺寸增加会降低组织弹性模数和硬度。具体目标1a：维生素D缺乏3周和4周后，生长期大鼠体内矿物质含量将会减少。治疗将通过全骨弯曲测试得到确认。将对组织弹性模数、成分和微观结构进行表征。组织成分和显微结构将与股骨和腰椎的压痕模数和硬度相关。特定目的1b：氟处理生长期大鼠3周和4周后，会产生矿化改变，削弱整个骨骼结构，改变矿物晶体大小。组织特性将按照特定目标1a进行分析和关联。假设2：代谢性酸中毒会产生基质变化，从而降低组织弹性模数。特定目的2：绵羊代谢性酸中毒是人类骨质疏松症的临床前模型，它减少了骨量并改变了组织矿化。在此绵羊模型中，组织属性将按照特定目标1进行分析和关联。此外，还将确定皮质标本的整体属性。结合微观结构细节的模型将被用来关联不同长度尺度的行为。假设3：双膦酸盐治疗增加了组织的弹性模数和硬度。具体目标3：双膦酸盐治疗将用于克服代谢性酸中毒后的骨质疏松症2.组织和体积特性将被分析并与特定目标2.我们将骨组织的组成和微观结构与弹性行为相关联，重点关注矿物质和胶原含量、晶体大小和胶原排列的作用。我们的方法将交叉关联几个微观水平的技术，这些技术以前没有被用来表征骨组织力学。

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.