Since the released products from degraded ECM can act as DAMPs, we sought to investigate whether the catabolic conditions influenced the immunomodulation of the formed NP-protein complexes (Figure ). Upon the formation of PCs in the joint space, NPs are exposed to interactions with immune cells. As first responders to the exposure of foreign particles, macrophages play a key role in the regulation of joint homeostasis by clearing tissue debris, mediating cellular communication, and promoting immunomodulatory processes within the joint. To investigate the potential for the NP-ECM complexes to induce immune responses, macrophages were stimulated with supernatants from the cartilage explant studies, and the produced cytokines were measured using a multiplex bead assay.