Sequential immunomodulation-osteogenesis by zinc-loaded nanotopographical fibrous membranes for inflammatory alveolar bone regeneration

• Developed a Zn 2+ -loaded nanotopographical PCL fibrous membrane via electrospinning and epitaxial crystallization. • The surface topography primarily inhibits M1 macrophage polarization, while Zn 2+ release promotes M2 polarization. • A synergistic immunomodulatory effect reshapes the osteoimmune microenvironment in periodontitis. • Sequential regulation of “immunomodulation first, osteogenesis second” enhances alveolar bone regeneration. • Provides a novel bioactive material strategy for treating inflammatory bone defects in periodontitis. The regeneration of alveolar bone defects resulting from periodontitis poses a significant challenge in dental medicine, as it involves coordinated regulation of multiple biological processes, including anti-inflammation, osteogenesis, and immunomodulation. While engineered fibrous scaffolds enabling sustained bioactive release and providing physical topographical cues have been developed, current materials still face limitations in effectively balancing immunomodulation with biocompatibility. Herein, we constructed a zinc-loaded nanotopographical polycaprolactone fibrous membrane (Zn 2+ @PT) via electrospinning to integrate immunomodulatory and osteogenic functions. In vitro studies demonstrated that the Zn 2+ @PT membrane effectively directs macrophage polarization toward the pro-regenerative M2 phenotype and enhances the osteogenic differentiation of bone marrow mesenchymal stem cells. In vivo results further revealed its ability to remodel the periodontitis immune microenvironment and boost alveolar bone regeneration. This work elucidates a synergistic mechanism between zinc ions and surface topography in promoting bone healing through a sequential regulatory logic, where early-stage immunomodulation paves the way for subsequent osteogenesis, providing a new material design strategy for sequentially regulated regeneration of inflammatory bone defects in periodontitis.