Over fifteen percent of the western population suffer from osteoarthritis. For severe disability, total joint replacement remains the onlty treatment. The ageing population is growing and their expectations for an active, high quality lifestyle is increasing. The number of knee joint replacements is predicted to increase five time by 2025. While technology for knee joint replacements has advanced considerably over the last decade, knee joint replacements do yet restore the natural function or provide the longevity expected for a population expecting - fifty more active years after fifty. An alternative is needed.We wil address the potential of regenerative biological scaffolds to re-engineer and regenerate the knee in early stage degenerative disease. We will build upon our successful research and clinical trials in the application of regenerative biological scaffolds in the cardiovascular system.. We will research and develop bioprocesses to produce a portfolio of tissue specific regenerative biological scaffolds to replace disrupted and degenerative tissues in the knee, including ligaments, meniscus, bone and cartilage. and evaluate their biomechanical, biotribological and biological function. We will investigate the regenerative potential of these novel biological scaffolds individually and collectively in the knee as a bioengineering system.This research will open the opportunity for a paradigm shift for treatment of degenerative disease in the knee and offer the potential for substantially delaying the need for a joint replacement in hundreds of thousands of patients every year.