Collaborative Research: Effect of Hormones on the Accumulation, Response, and Repair of Fatigue Damage in Anterior Cruciate Ligaments

This project will study how hormone levels affect knee injuries. In particular, the research will investigate whether different hormones alter the resilience of the anterior cruciate ligament. This tissue is a key stabilizer of the knee and is commonly torn during sports activities. The likelihood of anterior cruciate ligament tears is also different between men and women; however, the reason for this is unclear. This project will investigate whether the risk of anterior cruciate rupture is dependent on hormonal differences using a mouse model of anterior cruciate ligament injury. Additionally, it will create artificial ligaments from human and mouse cells to directly measure their response to stretching. In both cases, the research team will adjust the hormone levels in experiments and measure how cells in the anterior cruciate ligament respond to stretching. These data will help us understand how the anterior cruciate ligament becomes damaged and how well it repairs itself. This information can be used to develop strategies for preventing anterior cruciate ligaments based on a person’s unique risk for injury. This project will investigate whether hormones affect the accumulation and repair of fatigue damage in the anterior cruciate ligament due to changes in anterior cruciate ligament mechanobiology. While prior studies have investigated the effect of estrogen on anterior cruciate ligament mechanics and biology, how hormones impact remodeling of the anterior cruciate ligament in response to cyclic loading has not been studied. Importantly, the research will maintain important cell-cell and cell-matrix interactions by generating 3D ligament constructs from mouse and human cells to mechanistically study the interaction between estrogen and mechanotransduction pathways. This in vitro work will be complemented by an in vivo mouse model of anterior cruciate ligament fatigue injury along with gonadectomy to investigate the effect of hormones on the accumulation and repair of anterior cruciate ligament fatigue damage. These data will test the novel hypothesis that hormone levels alter the remodeling response of anterior cruciate ligament fibroblasts to mechanical loading, which leads to differences in tissue repair and functional recovery. Ultimately, these data may be used to develop personalized training protocols and biotechnologies to reduce the incidence of anterior cruciate ligament ruptures. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2539974 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Spencer Szczesny | Institution: Pennsylvania State Univ University Park, UNIVERSITY PARK, PA | Award Amount: $263,500 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2539974 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2539974.html