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Periodontitis is a chronic inflammation caused by dental plaque. It is characterized by the accumulation of excessive reactive oxygen species (ROS) and inflammatory mediators in the periodontal area. This affects the function of host cells, activates osteoclasts, and destroys periodontal tissue. Treatments such as local debridement or antibiotic therapy for ameliorating the overactive inflammatory microenvironment and repairing periodontal tissues are challenging. This paper reports multifunctional nanoplatforms (Se-CuSrHA@EGCG) based on sericin with ROS-scavenging, immunomodulatory, angiogenic, and osteogenic capabilities. The natural protein sericin, derived from silk cocoons, is used in water/oil emulsification and cross-linking processes to create sericin nanoparticles (Se NPs). Numerous binding sites are present on the surface of Se NPs. Ion-doped hydroxyapatite nanoparticles (Se-CuSrHA NPs) can be constructed using the force between positive and negative charges. After mineralization, an antioxidant coating is formed on the surface using polyethyleneimine (PEI)/epigallocatechin gallate (EGCG). Research conducted both in vitro and in vivo demonstrates that Se-CuSrHA@EGCG NPs can efficiently scavenge ROS, regulate macrophage polarization, increase the secretion of anti-inflammatory cytokines, and balance the immune microenvironment. In addition, Se-CuSrHA@EGCG stimulates angiogenesis, inhibits osteoclasts, and accelerates periodontal tissue repair. Therefore, this is a preferable strategy to accelerate bone regeneration in patients with periodontitis., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)