Evaluating the Efficacy of Combined P188 Treatment and Surgical Intervention in Preventing Post-Traumatic Osteoarthritis Following a Traumatic Knee Injury.

Previous studies have shown that reconstructive surgery alone following injury to the anterior cruciate ligament (ACL) does not prevent the development of post-traumatic osteoarthritis (PTOA). Poloxamer 188 (P188) has been shown to prevent cell death following trauma in both articular cartilage and meniscal tissue. This study aims to test the efficacy of single or multiple administrations of P188 in conjunction with reconstructive surgery to help prevent or delay the onset of the disease. Thirty skeletally mature rabbits underwent closed-joint trauma that resulted in ACL rupture and meniscal damage and were randomly assigned to one of four treatment groups with varying doses of P188. ACL reconstruction was then performed using an autograft from the semitendinosus tendon. Animals were euthanized 1-month following trauma, meniscal tissue was assessed for changes in morphology, mechanical properties, and proteoglycan content. Femurs and tibias were scanned using microcomputed tomography to determine changes in bone quality, architecture, and osteophyte formation. The medial meniscus experienced more damage and a decrease in the instantaneous modulus regardless of treatment group, while P188 treatment tended to limit degenerative changes in the lateral meniscus. Both lateral and medial menisci had documented decreases in the equilibrium modulus and inconsistent changes in proteoglycan content. Minimal changes were documented in the tibias and femurs, with the only significant change being the formation of osteophytes in both bones regardless of treatment group. The data suggest that P188 was able to limit some degenerative changes in the meniscus associated with PTOA and may warrant future studies.

Assessment of changes in the meniscus and subchondral bone in a novel closed-joint impact and surgical reconstruction lapine model.

Despite reconstruction surgery to repair a torn anterior cruciate ligament (ACL), patients often still show signs of post-traumatic osteoarthritis (PTOA) years following the procedure. The goal of this study was to document changes in the meniscus and subchondral bone due to closed-joint impact and surgical reconstruction in a lapine model. Animals received insult to the joint followed by surgical reconstruction of the ACL and partial meniscectomy. Following euthanasia of the animals at 1, 3, and 6-months post-impact, meniscal tissue was assessed for changes in morphology, mechanical properties and proteoglycan content. Femurs and tibias were scanned via micro-computed tomography to determine changes in bone quality, morphometry, and formation of osteophytes. Both the lateral and medial menisci showed severe degradation and tearing at all-time points, with higher degree of degeneration being observed at 6-months. Decreases in both the instantaneous and equilibrium modulus were documented in both menisci. Minimal changes were found in bone quality and morphometry, with most change documented in the tibia. Bones from the reconstructed limbs showed large volumes of osteophyte formations, with an increase in volume over time. The initial changes that were representative of PTOA may have been limited to the meniscus, but at later time points consistent changes due to the disease were seen in both tissues. This study, which builds on a previous study by this laboratory, suggests that the addition of surgical reconstruction of the ACL to our model was not sufficient to prevent the development of PTOA.