Ligaments develop in the periarticular mesenchymal tissue, with a layer of synovium separating them from the joint spaces. De- velopment of the ACL, for example, begins with fibroblasts aligning between the femoral and tibial attachment sites. Collagen fibrils are deposited between the cells, parallel to the longitudinal axis of the ligament. The organelles of the fetal and young adult rat ligament cells contain much rough endoplasmic reticulum and a prominent Golgi apparatus, which suggests that these are actively synthesizing cells. As the cells deposit more and more collagen, the bundles of matrix push the cells apart, thus forming the mature ligament with a lower density of cells and higher collagen content.

Studies of growth in rabbit medial collat- eral ligaments (MCLs) have demonstrated consistent elongation of the ligament, in con- trast to the focal centers of growth located at the physes (ie, growth plates) in long bones. At the site where ligament inserts into bone, bone cells divide rapidly, and the collagen of the ligament is incorporated into the bone. This active bone remodeling at the insertion site allows the ligament to move in concert with the longitudinal growth of the bone. Therefore, the ligament remains attached to the bone’s metaphyseal region.

Changes in cell content and ligament structure as a function of aging are not yet well known in humans. In animal models, however, it has been shown that the stiffness of the MCL of the knee reaches a maximum at maturity and then gradually declines. It is not yet known whether this phenomenon is present in all ligaments or in all species. The strength of the attachment of ligament to bone is also suspected to vary with age; adults tend to rupture their ACL in its mid- substance, whereas in skeletally immature patients, the injury more commonly occurs in a bony avulsion of the attachment site of the ligament.