Diabetes alters protein corona to reprogram wear particle-cell interaction

The long-term stability of biomedical hard-tissue implants is closely associated with the homeostasis of the surrounding immune microenvironment. Wear particles generated from implants can trigger immune activation, leading to local inflammatory responses and inducing bone destruction, ultimately resulting in implant failure. In addition, in patients with diabetes, chronic metabolic disturbances can disrupt immune homeostasis around implants, thereby increasing the risk of implant-related complications. Although the immunological effects of wear particles under normal physiological conditions have been extensively studied, their behavioral characteristics and immunological effects under metabolic disorder conditions such as diabetes remain insufficiently elucidated. Previous studies have demonstrated that nanoparticles rapidly acquire a protein corona (PC) upon exposure to biological fluids, which determines their immune recognition and interactions with cells. However, how diabetes-associated metabolic abnormalities remodel the PC on wear particles and thereby modulate immune responses has not been fully elucidated. In this study, we found that diabetes induces the formation of a distinct PC, referred to as DM-PC (Diabetic-derived protein corona). The DM-PC was enriched in receptor signaling-related proteins, enhancing interactions between wear particles and macrophage membrane receptors and activating the downstream JAK1-STAT3 pathway. The resulting immune imbalance significantly enhanced particle-induced M1 polarization and osteoclast activation. Collectively, this study proposes a mechanism by which the DM-PC modulates macrophage recognition of wear particles and enhances their inflammatory effects through an inflammation-amplifying signaling axis. These findings provide insight into how diabetes-associated metabolic dysregulation drives the progression of implant complications and offer potential intervention targets for improving the long-term stability of hard-tissue implants in the context of metabolic diseases. STATEMENT OF SIGNIFICANCE: Although the immunological effects of wear particles generated from hard-tissue implants under normal physiological conditions have been extensively investigated, their behavioral characteristics and biological effects in the context of metabolic disorders such as diabetes remain insufficiently elucidated. Given this, from the perspective of the protein corona, this study demonstrates that the diabetic microenvironment alters the interfacial biological properties of wear particles and reshapes their interactions with macrophages, thereby exacerbating inflammatory responses and bone destruction. This study not only elucidates the potential biological basis underlying the increased risk of hard-tissue implant-related complications in patients with diabetes, but also provides mechanistic rationale as well as potential strategies for the prevention or intervention of implant-related complications in diabetic individuals.