Cartilage Fracture Toughness By Micropenetration

描述(由申请人提供)： 本研究的目的是开发微渗透方法来测量小鼠和更大物种的软骨的断裂韧性，然后使用该方法在小鼠骨关节炎(OA)模型中检验关于骨关节炎(OA)病因的假说。 在前期工作中开发的理论和实验方法将被改进，并用于预测牛软骨的穿透深度和断裂韧性。为了验证该方法，预测的深度将与组织学测量的深度进行比较；预测的断裂韧性将与使用独立的宏观方法测量的断裂韧性进行比较。预测的断裂韧性对材料特性变化的敏感性将在胶原酶消化的牛软骨上进行评估。将先前建立的大变形、粘弹性有限元模型进行扩展，以帮助理解这一过程，并为数据简化提供一种替代方法。在I牛软骨上开发出该方法后，该程序将移植到小鼠软骨上。为了验证，预测的老鼠穿透深度将再次与组织学测量的深度进行比较。 在小鼠身上完成这些方法的开发后，它们将被用于测量不同年龄的STR/ORT小鼠和CBA小鼠的断裂韧性。STR/ORT小鼠是一种会发生早产性骨性关节炎的品系，CBA小鼠是一种不会发生早产性骨性关节炎的品系。小鼠软骨的组织学和扫描电子显微镜将被用来评估纤颤。数据将被用来检验在自然发生的骨性关节炎动物模型中软骨减弱先于纤颤的假设。

DESCRIPTION (provided by applicant): The goal of this research is to develop the method of micropenetration to measure the fracture toughness of cartilage in mice and larger species, and then use the method to test a hypothesis on the etiology of osteoarthritis (OA) in a mouse model of OA. Theoretical and experimental methods developed in preliminary work will be refined and used to predict depth of penetration and fracture toughness in bovine cartilage. To validate the method, predicted depth will be compared to that measured by histology; the predicted fracture toughness will be compared with fracture toughness measured using an independent macroscopic method. The sensitivity of predicted fracture toughness to changes in material properties will then be assessed on bovine cartilage subjected to digestion with collagenase. A large deformation, viscoelastic finite element model previously developed will be extended to aid in understanding the process and provide an alternative method for data reduction. After developing the method on I bovine cartilage, the procedures will be transferred to mouse cartilage. For validation, predicted depth of penetration in the mouse will again be compared with that measured by histology. After completing development of the methods in mice, they will be used to measure the fracture toughness in STR/ort mice, a strain that develops premature OA, and CBA mice, a strain that does not develop premature OA, at various ages. Histology and SEM of the mouse cartilage will be used Ito evaluate fibrillation. Data will be used to test the hypothesis that cartilage weakening precedes fibrillation in an animal model of naturally occurring OA.