Post-Traumatic Osteoarthritis: Biologic Approaches to Treatment

Joint injuries are becoming increasingly common, with young adults between the ages of 1844 seeking medical attention for joint sprains, dislocation, fractures, anterior cruciate ligament (ACL) and meniscal tears, and others. The cascade of events that follow these joint injuries have been shown to increase the risk of post-traumatic osteoarthritis (PTOA) by 2050% (Anderson et al,2011). Therefore, understanding biological responses that predispose to PTOA should help in determining treatment strategies to delay and/or prevent the progression of the disease. Ex vivo and in vivo studies (Anderson et al,2011;Buckwalter et al,2004;Furman et al, 2007; Guilak et al,2004; Hurtig et al, 2009) have provided evidence that the force and severity of the impact applied to the joint are among the risk factors involved in the development of PTOA. Recent research on the events that follow joint trauma have shown chondrocyte death and apoptosis, inflammation (elevation of caspases, selected proinflammatory cytokines, matrix fragments, nitric oxide, reactive oxygen species [ROS], etc.) and matrix damage/fragmentation to be early phase responses to injury. Together they lead to the development of OA-like focal cartilage lesions characterized by the loss of matrix constituents, surface fibrillation, and fissures that if untreated have a tendency to expand and progress to fully-blown disease. Currently, the only treatments available for joint trauma are surgical interventions, such as microfracture, articular chondrocyte transplantation, autografting, allografting, debridement and lavage. There are also some experimental approaches that involve engineering of cartilage with the use of juvenile cartilage, scaffolds and various polymeric matrices, but those are still in development. To the best of our knowledge none of them could regenerate normal adult hyaline cartilage that is able to perform required functions, sustain the load and integrate with the host tissue. Furthermore, newly repaired tissue, due to its imperfect structural organization, may also be more susceptible to re-injury, an important aspect that often remains forgotten. Therefore, there is an unmet need in the development of novel therapeutic approaches based on the mechanisms that drive the onset and progression of PTOA in order to stimulate biologic repair, delay or prevent the need of surgery, or when used together, improve the outcome of surgical interventions if biologics are applied prior, during, or soon after surgery. Based on our current understanding of the molecular and