Joint pain is a major cause of disability in middle-aged and older people 1. Pain usually results from degeneration of the joint’s cartilage due to primary osteoarthritis or from trauma causing loss of cartilage 1. As many as 36 million Americans su!er from some form of arthritis 2 and cartilage damage from sports injury is also common. It has been shown that up to 16% of injuries to the knee cause intra-articular bleeding 3,4. Since cartilage shows very little tendency for self-repair, these injuries are maintained for years and can eventually lead to further degeneration (secondary osteoarthritis) 4. Given the debilitating nature of severe joint pain, scientists and surgeons have tried for decades to repair or regenerate lost cartilage, but there has been little success due to the complex properties of the tissue and its essential function in the body. Hyaline cartilage, the type of cartilage found in joints, provides stable movement with less friction than any prosthetic replacement, and can alter its properties in response to di!erences in loading. Although appearing to be a simple, avascular matrix, hyaline cartilage possesses properties such as resistance * Correspondence address: Department of Bioengineering, Rice University, 6100 Main, MS 142, Houston, TX 77005-1892, USA. Tel.: #713-285-5355; fax: #713-285-5353. E-mail address: [email protected] (A.G. Mikos) to compression and the ability to distribute loads that cannot be fully replaced by any other tissue or device designed to date 5,6. This review will provide an overview of cartilage anatomy and types of injury, as well as focus on current strategies for cartilage repair in the knee joint, including promising new strategies involving tissue engineering. The knee, with two distinct articulating surfaces is a condylar-type joint. Both bones, the femur and the tibia, that comprise the joint are covered with a layer of hyaline cartilage at the joint surface. Immediately below this is the periosteal covering of the bone. The synovial membrane encircles the joint, thereby forming a barrier to retain the synovial #uid in the knee. This #uid provides lubrication and nutrients for the cartilage since no blood vessels penetrate into the tissue from the subchondral bone 7. Although only hyaline cartilage is found in the knee, two other kinds, “brocartilage and elastic cartilage, are seen in other areas of the body. All three are composed of chondrocytes and extracellular matrix macromolecules. Elastic cartilage forms the ear and nose and is characterized by the presence of elastin in the extracellular matrix (ECM). Fibrocartilage has a higher proportion of collagen in the ECM than hyaline cartilage and is found at the ends of tendons and ligaments in apposition to bone. Hyaline cartilage has a white, glassy appearance, and unlike “brocartilage, shows no macroscopic evidence of “bers 8.