Sequentially Releasing Aspirin and Osteogenic Growth Peptide Scaffold Modulates Immunity and Bone Homeostasis to Enhance Periodontal Bone Regeneration

Severe periodontitis, affecting 10% of the population, is characterized by chronic inflammation and bone loss. Given the limitations of current treatments, modulating inflammation and enhancing bone regeneration from an immunological perspective represent a promising strategy. This study developed a hierarchical drug delivery scaffold with an outer layer of poly(lactic- co -glycolic acid) loaded with aspirin and an inner core of poly(L-lactic acid) containing osteogenic growth peptide (OGP), fabricated via electrospinning. In the early implantation phase, the scaffold suppresses M1 and promotes macrophage M2 polarization, shifting the periodontal microenvironment from inflammatory to regenerative. At later stages, the release of the OGP enhances bone regeneration at the implant site. The sequentially releasing aspirin and OGP-Scaffold (As+OGP-Scaffold) demonstrate excellent biocompatibility and potent immuno-osteogenic effects both in vitro and in vivo . Bioinformatics and Western blot analyses show that the As+OGP-Scaffold modulates macrophage polarization by inhibiting the ERK-CREB axis and activating the STAT3 pathway while promoting osteogenesis through SMAD signaling pathways and suppressing osteoclast-associated MAPK signaling. This dual immuno-osteogenic approach offers a promising solution for periodontal bone regeneration in severe periodontitis.