COBRE: UD: PROJ 1: HEALING OF CARTILAGE AFTER EXPERIMENTALLY INDUCED OA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项多学科的研究将调查由于关节负荷改变而导致的骨关节炎发生后关节软骨的愈合情况。使用外固定加载装置的动物模型将通过施加内翻力矩来启动膝关节内侧间隙的骨关节炎改变。在去除负载后，模拟矫正手术干预，软骨将被允许愈合，并将在不同的时间点进行观察。关节软骨生物学的各个方面将用免疫组织学和免疫测定法进行评估。将使用机械测试来量化材料的行为。将建立一个新的数学模型，以获取结构的力学行为和软骨几何形状，并描述愈合过程中局部材料性能的变化。将对生物和生物力学结果进行比较。 在动物模型中，这两个实验因素将被控制：1)移除负载后的愈合时间；2)由骨关节炎启动加载装置施加的负载大小。结果测量将用于评估关节软骨在愈合期间的变化：1)材料特性通过材料测试测量的力学行为的数学模型确定；以及2)组织和细胞基质组成，从组织学和化验观察。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This multi-disciplinary study will investigate the healing of articular cartilage after the development of osteoarthritis due to altered joint loading. An animal model utilizing an external fixation loading device will initiate osteoarthritic changes in the medial compartment of the knee by applying a varus moment. After removal of the load, simulating a corrective surgical intervention, the cartilage will be allowed to heal and will be observed at different time points. Various aspects of articular cartilage biology will be assessed using immunohistology and immunoassay. Mechanical testing will be used to quantify the material behavior. A novel mathematical model will be formulated to take the structural mechanical behavior and cartilage geometry and describe changes in the localized material properties during healing. Comparisons will be made between biological and biomechanical outcomes. The two experimental factors will be controlled in the animal model: 1) time of healing after removal of the load; and 2) load magnitude applied by the osteoarthritis-initiating loading device. Outcome measures will be used to assess the changes in the articular cartilage during the healing period: 1) material properties determined from mathematical modeling of the mechanical behavior as measured from material testing; and 2) tissue and cellular matrix composition as observed from histology and assay.