Effects of Blood and Blood-Derived Products on Meniscus Healing

ABSTRACT. Meniscus tears are common sports-related injuries and are associated with injuries to the anterior cruciate ligament (ACL) in up to 70% of cases. Acute hemarthrosis (bleeding into the joint) occurs with ACL tears, peripheral meniscus tears, and intra-articular fractures. Traumatic injuries to the meniscus cause acute pain and joint immobility, and frequently lead to post-traumatic osteoarthritis (PTOA). However, the exact mechanism(s) by which PTOA develops following these traumatic injuries is unknown. Recently, bleeding from femoral drill holes in a rabbit model showed increased inflammatory and catabolic gene expression in the meniscus tissue. Furthermore, a variety of blood-derived orthobiologics, including platelet rich plasma (PRP), are utilized as potential therapeutic tools to enhance meniscus repair, despite the lack of a thorough understanding of the effects of these products on meniscus tissue. Therefore, it is critical to perform well-controlled studies that evaluate the factors that impact meniscus repair in the injured joint microenvironment. Currently, there is a gap in knowledge regarding the direct effects of blood and blood-derived components on meniscus tissue, and there is controversy related to the effectiveness of certain blood-derived orthobiologics as therapy for meniscal injuries. Consequently, our overall goal is to elucidate the effects of blood and blood-derived components on meniscus tissue homeostasis, repair, and PTOA development. In this proposal, we will elucidate the biological drivers of blood-mediated meniscus tissue catabolism and determine the effects of acute hemarthrosis and blood-derived orthobiologics on meniscus repair and PTOA development. We hypothesize that blood-derived immune cells mediate catabolism of meniscus tissue, prevent meniscus repair, and exacerbate PTOA development, and also reduce the effectiveness of orthobiologics for meniscus repair. In Aim 1, we will determine the effects of blood components on meniscus tissue homeostasis and the biological drivers of blood-mediated meniscus tissue degeneration. In Aim 2, we will elucidate the consequences of hemarthrosis on meniscus tissue repair and PTOA development. In Aim 3, we will determine the effects of PRP on meniscus homeostasis, repair, and PTOA development. There is a critical clinical need to understand the effects of blood-derived factors on meniscus healing and PTOA development. The results of this work will likely improve both surgical and non-surgical outcomes, and lead to the development of new orthobiologics.