The knee joint is the most commonly injured body part in the human body. Injuries as a result of participation in sports, or other recreational activities, often leads to damage to the anterior cruciate ligament (ACL) and meniscus. Injury to these tissues are strongly associated with subsequent knee post-traumatic osteoarthritis (PTOA), which is considered a serious disease because it greatly impacts a patient’s quality of life and significantly increases their risk of premature death. It is estimated that PTOA accounts for 12% of the roughly 30 million Americans that show signs of osteoarthritis (OA). To return stability to the joint, the current clinical treatment is to perform reconstruction of the torn ACL and a meniscal debridement, or meniscectomy, when needed. However, long term studies have shown that surgical intervention does not prevent the onset or progression of PTOA. It is believed that reconstruction surgery fails to address the occult damage to the soft tissues within the knee joint at the cellular level. Recently, a single dose of the amphipathic and nonionic surfactant Poloxamer 188 (P188) has been shown to be an effective inhibitor of acute cell death and inhibit pathways associated with inflammation in articular cartilage in both in-vitro and in-vivo studies.
This project strives to test if combined surgical and P188 treatment following injury to the ACL will help prevent PTOA in an in-vivo closed-joint traumatic injury model. It is hypothesized that combined treatment will mitigate or delay the progression of the disease joint by returning normal knee kinematics and restoring the integrity of damaged cell membranes in the soft tissues. Thus, the aims of the proposed project are to:
- Determine the efficacy of a single and multiple temporal administrations of P188 in inhibiting cell death following traumatic impact in meniscal tissue.
- Assess morphological, functional and histological changes in the meniscus
- Evaluate chronic changes in subchondral cortical and trabecular bone of femurs and tibias
- Determine the presence of biomarkers associated with PTOA in the synovial fluid
Finding solutions to prevent the onset of PTOA, in conjunction with ACL reconstructive surgery, would provide a novel treatment to improve the quality of life for millions of people and decrease their risk of premature death.