As the most common chronic degenerative joint disease, osteoarthritis (OA) is the leading cause of pain and physical disability, affecting millions of people worldwide. Mainly characterized by articular cartilage degradation, osteophyte formation, subchondral bone remodeling, and synovial inflammation, OA is a heterogeneous disease that impacts all component tissues of the articular joint organ. Pathological changes, and thus symptoms, vary from person to person, underscoring the critical need of personalized therapies. However, there has only been limited progress towards the prevention and treatment of OA, and there are no approved effective disease-modifying osteoarthritis drugs (DMOADs). Conventional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy, are still the major remedies to manage the symptoms until the need for total joint replacement. In this review, we provide an update of the known OA risk factors and relevant mechanisms of action. In addition, given that the lack of biologically relevant models to recapitulate human OA pathogenesis represents one of the major roadblocks in developing DMOADs, we discuss current in vivo and in vitro experimental OA models, with special emphasis on recent development and application potential of human cell-derived microphysiological tissue chip platforms.

The production of veritable in-vitro models of bone tissue is essential to understand the biology of bone and its surrounding environment, to analyze the pathogenesis of bone diseases (e.g., osteoporosis, osteoarthritis, osteomyelitis, etc.), to develop effective therapeutic drug screening, and to test potential therapeutic strategies. Dysregulated interactions between vasculature and bone cells are often related to the aforementioned pathologies, underscoring the need for a bone model that contains engineered vasculature. Due to ethical restraints and limited prediction power of animal models, human stem cell-based tissue engineering has gained increasing relevance as a candidate approach to overcome the limitations of animals and to serve as preclinical models for drug testing. Since bone is a highly vascularized tissue, the concomitant development of vasculature and mineralized matrix requires a synergistic interaction between osteogenic and endothelial precursors. A number of experimental approaches have been used to achieve this goal, such as the combination of angiogenic factors and three-dimensional scaffolds, prevascularization strategies, and coculture systems. In this review, we present an overview of the current models and approaches to generate in-vitro stem cell-based vascularized bone, with emphasis on the main challenges of vasculature engineering. These challenges are related to the choice of biomaterials, scaffold fabrication techniques, and cells, as well as the type of culturing conditions required, and specifically the application of dynamic culture systems using bioreactors.