Lower back and neck pain are leading physical conditions for which patients see their doctors in the United States. The organ commonly implicated in this condition is the intervertebral disc (IVD), which frequently herniates, ruptures, or tears, often causing pain and limiting spinal mobility. To date, approaches for replacement of diseased IVD have been confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Here we present the evaluation of a living, tissueengineered IVD composed of a gelatinous nucleus pulposus surrounded by an aligned collagenous annulus fibrosus in the caudal spine of athymic rats for up to 6 mo. When implanted into the rat caudal spine, tissue-engineered IVD maintained disc space height, produced de novo extracellular matrix, and integrated into the spine, yielding an intact motion segment with dynamic mechanical properties similar to that of native IVD. These studies demonstrate the feasibility of engineering a functional spinal motion segment and represent a critical step in developing biological therapies for degenerative disc disease.regenerative medicine | total disc replacement | biomaterials | disc arthroplasty | image-based A mong the most common physical conditions for which patients see their doctors are back and neck pain, which carry an estimated annual cost to society up to $100 billion (1). Current conservative and operative treatment options are mostly palliative in nature and fail to restore function to the spine. The most common target for treatment of back and neck pain is the intervertebral disc (IVD) (2-5). IVD degeneration is characterized by loss of proteoglycan, loss of disc height, annulus fibrosus (AF) damage and tears, spondylolisthesis, spinal stenosis, herniated discs, neoinnervation, hypermobility, and inflammation (6-8). Conservative treatments including medication and physiotherapy are the first line of defense in treating these disorders. Despite these treatments, it is estimated that between 1.5 and 4 million patients in the United States await surgical intervention (9).Such surgical interventions may involve the removal of herniated tissue or the entire IVD and replacing it with a mechanical device designed to either fuse the adjacent vertebrae or to preserve some motion. Regardless of approach, motion segment mobility is altered, often precipitating degeneration in adjacent motion segments (10). Nonbiological total disc replacement implants were developed to avoid this loss of motion at the operated level, and as a result, reduce the incidence of adjacent segment disease. The efficacy of such implants is a matter of much debate (11-13); however, it is clear that nonbiological total disc replacement implants suffer from failure modes commonly associated with traditional metal/polyethylene arthroplasty, such as mechanical failure, dislodgement, polyethylene wear, and associated osteolysis and implant loosening. More recently, increasing attention has been turned toward creating tissue engineer...