Modulating the osteoimmune microenvironment: biomaterial strategies for bone regeneration and implant integration

Bone regeneration and implant integration depend not only on osteoconductive architecture and osteogenic cues, but also on the immune environment established immediately after material implantation. The concept of osteoimmunology has shifted biomaterial design from immune avoidance toward controlled immune instruction. In this view, protein adsorption, coagulation, innate immune cell recruitment, macrophage polarization, neutrophil activity, vascularization, and osteogenesis are temporally linked events rather than isolated biological responses. Drawing predominantly on preclinical evidence, this review summarizes how biomaterials modulate the osteoimmune microenvironment through two complementary routes. First, material-intrinsic properties, including surface topography, porosity, chemistry, hydrophilicity, charge, coatings, and bioactive ion release, provide physical and chemical cues that shape immune cell behavior and downstream bone formation. Second, biomaterial-enabled delivery of cytokines, chemokines, growth factors, nucleic acids, and extracellular vesicles enables more active reprogramming of inflammatory and regenerative niches. We further discuss how disease contexts, such as diabetes, osteoporosis, infection, and aseptic loosening, alter osteoimmune responses, and how current models, outcome measures, manufacturing stability, and regulatory requirements constrain translation. A central message is that osteoimmune biomaterial design should match immune timing, control inflammatory intensity, couple immune, vascular and osteogenic repair, and be evaluated in the relevant pathological microenvironment. Future progress will require standardized evaluation systems, mechanistic validation across complex in vivo models and scalable material platforms with reproducible immune effects.