Biomechanical Simulations of Progressing Osteoarthritis to Advance Understanding and Therapies

进展性骨关节炎的生物力学模拟以促进理解和治疗

• 批准号: 1662429
• 负责人: David Pierce
• 金额: $ 40万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1662429&HistoricalAwards=false
• 关键词: Biomechanical; Simulations; Progressing; Osteoarthritis; Advance

The objective of this project is to understand the influence of intra-tissue stress distributions on the progression of osteoarthritis (OA) in human cartilage by leveraging new mechanical and imaging experiments, novel simulations of evolving virtual human cartilage in vivo, and multiple images of the knee from the NIH-funded Osteoarthritis Initiative (OAI) database. OA is a disease of the synovial joint, with degeneration and loss of articular cartilage as one hallmark change. Mechanical stresses play a key role in the destructive evolution of the disease. Both overloading (e.g. trauma) and reduced loading (e.g. immobilization) of cartilage induce molecular and microstructural changes that lead to mechanical softening, fibrillation, and erosion. Crucially, there is currently no direct method to correlate spatially resolved intra-tissue stresses with progression of OA in individual patients. Events with the Connecticut Science Center's Women in Science Initiative will spark STEM interest in female middle school students. High school, undergraduate and graduate students will perform new experiments and establish simulations.The primary hypothesis is that intra-tissue stresses (e.g. maximum shear stresses) will more strongly correlate with structurally defined OA progression measured by changes in both the network of collagen fibers (organization and density) and gross tissue volume, than with corresponding strains. Objective 1 establishes chemo-biomechanical constitutive relations for evolving OA ex vivo by measuring the large-shear stress-strain response of OA human cartilage; imaging the corresponding cell viability, composition, and microstructure; establishing functions describing the turnover of structurally significant cartilage constituents; and incorporating these within a custom simulation framework. Objective 2 establishes and validates simulations of evolving virtual human cartilage in vivo by establishing patient-specific models using the OAI data; training simulations to produce measured time-course outcomes; performing sensitivity and statistical analyses; and performing validation studies using additional OAI patients. The studies will link physical activity, and the resulting mechanical stimuli, to progression of OA and loss of cartilage function.

该项目的目的是了解组织内应力分布对骨关节炎（OA）在人体软骨中进展的影响，通过利用新的机械和成像实验，体内虚拟人体软骨的新模拟，以及来自NIH资助的骨关节炎倡议（OAI）数据库的多个膝关节图像。OA是一种滑膜关节疾病，关节软骨退化和丧失是一个标志性变化。机械应力在疾病的破坏性演变中起关键作用。软骨的过载（例如创伤）和负载减少（例如固定）都会引起分子和微观结构的变化，导致机械软化、原纤化和侵蚀。至关重要的是，目前还没有直接的方法来关联空间分辨组织内应力与个别患者的OA进展。 与康涅狄格科学中心的妇女在科学倡议的活动将激发女中学生干的兴趣。高中生、本科生和研究生将进行新的实验并建立模拟。主要假设是组织内应力（例如最大剪切应力）与结构定义的OA进展（通过胶原纤维网络（组织和密度）和总组织体积的变化测量）的相关性比与相应的应变的相关性更强。目的1通过测量OA人软骨的大剪切应力-应变响应，建立化学-生物力学本构关系，用于体外发展OA;对相应的细胞活力、组成和微观结构进行成像;建立描述结构上重要的软骨成分的周转的函数;并将这些纳入自定义模拟框架。目标2：通过使用OAI数据建立患者特定模型，建立并验证体内进化虚拟人体软骨的模拟;训练模拟以产生测量的时间过程结果;进行敏感性和统计分析;并使用其他OAI患者进行验证研究。这些研究将把身体活动和由此产生的机械刺激与OA的进展和软骨功能丧失联系起来。

项目成果

The evolving large-strain shear responses of progressively osteoarthritic human cartilage

• DOI: 10.1016/j.joca.2018.12.025
• 发表时间: 2019-05-01
• 期刊: OSTEOARTHRITIS AND CARTILAGE
• 影响因子: 7
• 作者: Maier, F.;Lewis, C. G.;Pierce, D. M.
• 通讯作者: Pierce, D. M.

Spatial Gradients of Quantitative MRI as Biomarkers for Early Detection of Osteoarthritis: Data From Human Explants and the Osteoarthritis Initiative

定量 MRI 的空间梯度作为骨关节炎早期检测的生物标志物：来自人类外植体和骨关节炎倡议的数据

• DOI: 10.1002/jmri.28471
• 发表时间: 2022
• 期刊: Journal of Magnetic Resonance Imaging
• 影响因子: 4.4
• 作者: Wilson, Robert L.;Emery, Nancy C.;Pierce, David M.;Neu, Corey P.
• 通讯作者: Neu, Corey P.

Mechanical Testing of Type II Collagen Networks: Towards Modulating Mechanics, Identifying Single-Fiber Properties, and Establishing Multiscale Models

II 型胶原网络的机械测试：调节力学、识别单纤维特性并建立多尺度模型

• 发表时间: 2021
• 期刊: Bioengineering and Biotransport Conference (SB3C
• 作者: Szarek, P.;.Pierce, D.M.
• 通讯作者: .Pierce, D.M.

Manipulating the Initiation and Propagation of Microcracks in Collagen Networks of Cartilage

操纵软骨胶原网络中微裂纹的产生和传播

• 发表时间: 2021
• 期刊: Bioengineering and Biotransport Conference (SB3C
• 作者: Santos, S.;Neu, C.P.;Samolyk, B.;Pierce, D.M.
• 通讯作者: Pierce, D.M.

TOWARD QUANTIFYING CHANGES IN THE COLLAGEN NETWORK OF HUMAN ARTICULAR CARTILAGE DURING EARLY-STAGE OSTEOARTHRITIS

量化早期骨关节炎期间人体关节软骨胶原蛋白网络的变化

• 发表时间: 2019
• 期刊: USA
• 作者: Szarek, P.E.;Lilledahl, M.B.;Lewis, C.G.;Pierce, D.M.
• 通讯作者: Pierce, D.M.