Degenerative intervertebral disc disease is a very common problem and currently there is no optimal treatment for individuals who develop persistent back disease as a result of this disease. Although back pain is rarely life-threatening, the annual cost in terms of lost productivity, medical expenses and workers' compensation benefits was estimated at $50 billion in 1998 in the United States. The long term goal of our research is to generate using a bioengineering approach a spinal unit in vitro that has tissue, which structurally and functionally approaches that of a natural intervertebral disc and is suitable as replacement for a damaged disc. Additionally this model can be used to investigate mechanisms regulating disc tissue formation, maintenance, and degeneration in vitro to identify new ways to regenerate disc tissue or new therapeutic agents to treat or prevent the disease. Our immediate aim is to develop a model of a spinal unit consisting of intervertebral disc tissue and cartilage endplate formed on and anchored into a porous bone substitute material. The specific aims of this proposal are: 1) To design a porous biodegradable polymeric scaffold made of silk with an organization to allow guided tissue formation to mimic the in vivo annulus fibrosus organization. 2) To form annulus fibrosus tissue in vitro, utilizing the silk scaffold. Annulus fibrosus cells will be seeded into the scaffold. The cells will be allowed to form tissue in a bioreactor in the presence or absence of a mechanical force (compression and/or shear). An optimal loading regime defined by amplitude and duration offeree application will be determined and the effect of this in vitro mechanical stimulation on tissue composition, collagen organization, and mechanical properties will be determined. 3) To generate a model of portion of a spinal unit composed of in vitro-formed annulus fibrosus tissue surrounding the nucleus pulposus, cartilage integrated with the top surface of a bone substitute (calcium polyphosphate). The viability and mechanical properties of the tissue will be evaluated.