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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这项多学科的研究将探讨由于关节负荷改变而导致骨关节炎后关节软骨的愈合。使用外固定载荷装置的动物模型将通过施加内翻力矩在膝关节内侧腔室引发骨关节炎变化。去除负荷后，模拟矫正手术干预，允许软骨愈合，并在不同的时间点观察。关节软骨生物学的各个方面将使用免疫组织学和免疫分析进行评估。机械测试将用于量化材料的性能。一个新的数学模型将被制定，以采取结构力学行为和软骨几何形状，并描述局部材料性能在愈合过程中的变化。将对生物学和生物力学结果进行比较。在动物模型中控制两个实验因素：1)卸荷后愈合时间；2)引发骨关节炎的加载装置所施加的载荷大小。结果测量将用于评估关节软骨在愈合期间的变化：1)材料性能通过材料测试测量的力学行为的数学模型确定；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.