ABSTRACT Recent data indicates that the fastest rising rates of anterior cruciate ligament (ACL) injuries of the knee are reported in children and adolescents with significant growth remaining. In the skeletally immature patient population, surgical reconstruction is increasingly suggested for complete ACL tears. However, the choice of non-surgical treatment or immediate surgical reconstruction of ACL tears remains a subject of debate in young patients with significant growth remaining or in the case of partial tears involving one ACL bundle. Sex appears to be a major risk factor for ACL injury during adolescence, but not in childhood, adding another layer of complexity. For both complete and partial ACL injuries, treatment algorithms have been developed without considering the potential sex- and age-dependent function of the ACL, due to the paucity of available data. Thus, the objective of this proposal is to determine how age and sex impact ACL maturation and joint function during skeletal growth and to assess if this knowledge can be applied to improve treatment after ACL injury. Aim 1 will determine how sex impacts the maturation of the ACL as well as that of its individual AM and PL bundles during skeletal growth. Aim 2 will determine how age and sex impact the immediate loading of secondary tissues in-vitro and the remodeling response of the joint in-vivo following loss of function of the AM bundle, PL bundle, or the entire ACL. Aim 3 will determine how replacement graft type and placement should vary to restore age- and sex-specific ACL and joint function. Successful completion of these aims will provide a basic science foundation for the development of age- and sex-specific algorithms for the treatment of ACL injuries. !