Co-delivery of icariin and stem cells via fibrinogen-modified PLGA composite microscaffolds for periodontitis-related alveolar bone repair

Periodontitis is a chronic inflammatory disease that progressively destroys periodontal tissues and alveolar bone, posing a significant challenge for clinical regeneration. Tissue engineering strategies integrating stem cells, biomaterials, and bioactive agents hold promise for overcoming the limitations of current periodontal regenerative approaches. In this study, we developed an injectable PLGA composite microscaffold-based co-delivery system with a porous architecture for the combined delivery of icariin (ICA) and bone marrow-derived mesenchymal stem cells (BMSCs). ICA-loaded PLGA composite microscaffolds (ICA-PLGA) were fabricated by a double emulsion–solvent evaporation method, followed by fibrinogen (Fg) surface modification via electrostatic layer-by-layer assembly to generate ICA-PLGA-Fg microscaffolds with improved cell-adhesive properties. These porous microscaffolds exhibited sustained ICA release for up to 28 days and enhanced BMSC adhesion and spreading. In vitro, ICA-PLGA-Fg supported favorable cytocompatibility and enhanced osteogenic differentiation of BMSCs under inflammatory conditions. In vivo, BMSC-seeded ICA-PLGA-Fg constructs implanted into rat periodontitis-related alveolar bone defects achieved markedly greater bone regeneration compared with both periodontitis and PLGA-only controls. Collectively, this co-delivery platform integrates sustained ICA release with a bioactive, cell-supportive microscaffold interface, promotes osteogenic responses in vitro, and shows therapeutic promise for enhancing periodontal bone repair in vivo.