Up to 350 wDegenerative joint diseases, e.g., osteoarthritis, contribute to physical disabilities. Current treatments for osteoarthritis, e.g., anti-inflammatory drugs, provide only short-term pain relief. Tissue engineering/regenerative medicine, which encompasses translational application of cells/scaffolds/biological signals, is a promising approach to repair damaged/diseased tissues to restore joint function/mobility. Adult mesenchymal stem cells (MSCs), e.g., from bone marrow and adipose, with multi-lineage differentiation potential, including chondrogenesis, are a promising cartilage repair cell type. A critical component to successful cell-based cartilage tissue engineering is a biocompatible/differentiation-supportive biomaterial cell-carrier scaffold. We have recently custom-designed photocrosslinked hydrogel scaffolds capable of live cell encapsulation during fabrication, with excellent cell retention/viability/differentiation, and generated robust cartilage/bone tissue constructs. Optimized scaffolds also allow controlled delivery of chondroinductive biofactors and anti-hypertrophy agents to improve the quality of the MSC-derived engineered cartilage. Custom-designed, cell-encapsulated constructs may be formed in-situ for joint cartilage re-surfacing, potentially amenable to minimally invasive, arthroscopic procedures. We have recently applied 3D-printing and a custom-designed microbioreactor to fabricate an MSC-derived, biphasic microtissue analogue of the osteochondral junction of the articular joint. This osteochondral microphysiological system is currently being used, coupled with additional tissue constructs simulating the infrapatellar fat pad (adipose) and synovium, as a joint tissue chip (microJoint) with a synovial fluid component, to model in-vitro osteoarthritis pathogenesis, e.g., exposure to pro-inflammatory agents, and to study biological and pharmacological influences on osteochondral health. The microJoint is being used as a human cell-based platform to screen for disease-modifying osteoarthritis drugs as well as to identify the cellular/molecular targets of osteoarthritis-associated pain.ords. No references allowed. Abstracts may be submitted at a later date.