Biomaterial regulation of excessive inflammation restores osteoimmune homeostasis in diabetic bone regeneration.

Diabetes mellitus markedly increases the incidence of fractures, implant failure and nonunion, primarily because chronic low-grade inflammation and a disrupted bone microenvironment impair regeneration. Under physiological conditions, coordinated interactions among immune, stromal, vascular and neural cells ensure timely initiation and resolution of inflammation, thereby maintaining osteoimmune homeostasis and supporting bone repair. In diabetes, hyperglycemia-induced oxidative stress, advanced glycation end products, impaired vascularization and 'inflammatory memory' prolong and intensify inflammatory responses. This excessive and unresolved inflammation disturbs immune-bone crosstalk, alters macrophage and T-cell phenotypes and uncouples osteogenesis and angiogenesis, ultimately hindering bone regeneration. This review summarizes the cellular and molecular basis of osteoimmune homeostasis and outlines how diabetes disrupts this regulatory network at systemic and local levels. We further highlight biomaterial strategies designed to modulate excessive inflammation and restore osteoimmune balance in diabetic bone regeneration, including localized delivery systems, cell-derived and extracellular vesicle-based agents, nanozyme-mediated microenvironmental regulation and immune-instructive physicochemical biomaterials. Finally, we discuss the critical hurdles of clinical translation (e.g. standardized scalable fabrication and long-term biosafety) and highlight multifactor integrated, logic-gated designs and systemic diabetes management strategies for advancing next-generation biomaterials for diabetic bone regeneration.