Inorganic Biomaterials as Immunomodulators: Dual Strategies for Activation and Suppression

• • Inorganic biomaterials exhibit dual immunomodulatory capacities: activation via adjuvant effects, ICD induction, and metabolic reprogramming; suppression via ROS scavenging and modulation of inflammatory cells, with specific examples including nano-ceria-loaded Mg-Al layered double hydroxide for rheumatoid arthritis therapy (Adv Sci, 2024, 11: 2307094). • • ROS-scavenging capabilities are demonstrated by ultrathin hafnium disulfide (HfS2) atomic crystals with colon-targeting for inflammatory bowel disease treatment (ACS Nano, 2022, 16: 15026–15041), indicating precise elimination of excessive ROS to restore immune tolerance. • • Photothermal regulation of macrophage polarization using 2D Ti3C2Tx MXene nanosheets enhances immunomodulatory osteogenesis (Colloid Interface Sci Commun, 2023, 56: 100733), showing that inorganic materials can direct immune cell fate for tissue regeneration. • • Tumor microenvironment-activated nanocomposite for self-amplifying chemodynamic/starvation therapy enhanced IDO-blockade tumor immunotherapy (Adv Sci, 2023, 10: 2303580) demonstrates integration of catalytic activity and immune checkpoint blockade, addressing low tumor immunogenicity and immunosuppressive TMEs.