(A) Through simulating different aspects of arthritis in humans, both joint-on-a-chip (in vitro) and animal models (in vivo) provide valuable information on predicting drug safety and efficacy in humans. Before joint-on-a-chip can be used as a preclinical model, cross-check of treatment outcomes from three systems, indicated by ① ② ③, with clinically tested drugs, is essential. (B) To define the fidelity of joint-on-a-chip and animal models in simulating human arthritis and response to treatments, harvested tissues and fluids can be analyzed with different methods. ELISA: enzyme-linked immunosorbent assay.