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.
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