How Emerging Nanomaterials are Effective in Bone Regeneration?

Bone defects remain challenging due to microenvironment disruption and immune imbalance. Traditional grafts offer structural support; however, they do not actively modulate this pathological niche. This review underscores smart nanomaterial reservoirs for bone regeneration, focusing on their capacity to remodel the hostile microenvironment and restore immune homeostasis. Key pathophysiological barriers, including vascular disruption, macrophage imbalance, and oxidative stress-induced ferroptosis, are identified as therapeutic targets. Additionally, fundamental nanoscale building blocks (rigid inorganic, polymeric, and inorganic piezoelectric materials) are critically compared, with an expanded focus on emerging technologies such as versatile nanofibers and 3D-printable bio-ink formulations. These components can be assembled into smart reservoirs (hydrogels, exosomes, and 3D scaffolds), enabling stimuli-responsive therapeutic delivery (pH, reactive oxygen species, and enzymes). By reprogramming intercellular communication and promoting M1-to-M2 macrophage polarization, these reservoirs restore osteoimmune homeostasis and couple osteogenesis with angiogenesis. Finally, translational challenges and future directions toward dynamically adaptive nanomedicines are discussed.