Osteoarthritis represents one of the most common joint degenerative diseases in the western world, affecting ~ 50% of the population above the age of 65. Cartilage is an avascular tissue characterized with zonal organizations, which play an important role in maintaining cartilage structure and functions. There remains a critical need to develop enabling novel technologies for regenerating cartilage with tissue-mimicking zonal organization. By infusing principles and concepts from stem cell biology, materials science, tissue engineering, and microfabrication, current bottlenecks in stem cell biology and tissue regeneration cannot be addressed using the existing models and paradigms. My proposed research will enable regeneration of cartilage with tissue-mimicking zonal structure and functions, and facilitate high-throughput screening of stem cell-niche interactions using novel gradient hydrogels.