Fibrocartilage is a type of tissue, such as that in the knee meniscus, that consists of aligned fibrous microdomains with nonfibrous proteoglycan-rich microdomain inclusions. The role of these different domains in growth and development, aging, and disease is not well understood. Dawn M. Elliott of the University of Delaware, Robert L. Mauck of the University of Pennsylvania, and coworkers have now quantified the proteoglycan microdomains in knee fibrocartilage from fetal, juvenile, and adult cows and from adult humans and assessed the tissue’s response to strain (Nat. Mater. 2016, DOI: 10.1038/nmat4520). The number of proteoglycan microdomains reached a steady state at the juvenile stage, they found, but the size of the proteoglycan domains continued to increase throughout aging. In humans, the size, but not the number, of inclusions correlated with age, body mass index, and diagnosis of osteoarthritis. The researchers separately engineered fibrocartilage by seeding cells on a polymer scaffold. One type of cell deposits the collagen matrix, and another type of cell deposits proteoglycans. The mechanical and signaling response of the engineered tissue to tensile strain matched that of the natural tissue. The engineered tissue thus provides a new tool for scientists to develop treatments for disease or injury, the researchers conclude.