Biomechanics and Mechanobiology of Impacted Cartilage: In-Vitro and In-Vivo Studies

Osteoarthritis (OA) is one of the most prevalent diseases in the United States and also in the world. Cartilage plays a vital role in articular joints and its structural integrity and mechanical properties are diminished by OA. Post traumatic osteoarthritis (PTOA) is a prevalent type of OA and occurs after a significant joint injury. Currently, no treatments are available to prevent or delay the progression of any form of OA. Collagen crosslinking improves the material properties of cartilage and has been proposed as a potential treatment for OA. The wear resistance of cartilage that had been crosslinked with CASPc, a light activated crosslinking agent , was tested . Results suggested that photo-initiated crosslinking improves the wear characteristics of cartilage. Another treatment for PTOA is through biological intervention. Preliminary data from our lab showed that metformin rescues the chondrocyte response to injurious impact overloading in the initial 24 hours following impact. However, whether this treatment maintained cartilage integrity for an extended duration had not been investigated. Material properties of cartilage were analyzed with an indentation test at different time points post-impact to determine the functional effect of cartilage injury and metformin treatment. Changes in the composition of the cartilage were investigated through biochemical techniques. Having an in vivo model for PTOA is key for testing any new therapeutic intervention. In this study a model was developed to deliver a consistent impact load to the posterior aspect of medial condyle of a rabbit knee. A drop tower was designed for impacting the rabbit knee , and load and acceleration were measured during the impact. A k-wire was passed through the condyles in the medial-lateral direction under the impact site to secure the condyle during the impact. Whether the impact parameters were affected by the location of the k -wire was evaluated. The location of the k-wire was varied in the anterior/posterior and proximal/distal directions in a knee joint of cadaveric rabbits and impact parameters were recorded. Multiple linear regression showed a correlation between the location of the k-wire and peak stress, loading rate, impact duration and work. Moreover a correlation was found between the damage induced to the cartilage and loading rate, impact duration and peak stress. This study indicated that k-wire location is critical to prevent fracture of the subchondral bone. A pilot study was designed to investigate the in-vivo effect of the metformin treatment on PTOA. Impacted knee joints in rabbits were treated with intraarticular metformin or were untreated controls. At 12 weeks post-injury, the progression of OA in the rabbit knees was quantified by histology, and OA severity was assessed using OA Research Society International (OARSI) scoring. Although the number of animals in the study were limited, intraarticular metformin appeared to prevent the development of PTOA in the impacted rabbit knees.