Abstract

Periodontitis is characterized by a self-sustaining pathophysiological cycle in which bacterial infection propagates destructive inflammation and oxidative stress, compromises tissue repair capacities, and facilitates recurrent infection. Current monotherapeutic strategies exhibit limited efficacy against this multifactorial pathology. Although resveratrol (RSV) exhibits significant anti-inflammatory and antioxidant activities, its clinical application is limited by poor solubility and suboptimal bioavailability. Herein, we fabricate a kind of injectable composite microspheres (RSV@Lipo@PMS) that encapsulate RSV-loaded cationic liposomes into polydopamine-modified alginate microspheres. This design leverages the synergistic interplay among the therapeutic bioactivity of RSV, the inherent antibacterial function of cationic liposomes, and the sustained retention afforded by the adhesive microcarriers. The composite system demonstrates robust reactive oxygen species (ROS) scavenging capacity, effectively suppresses lipopolysaccharide-induced inflammation in macrophages, and potently enhances bactericidal efficacy against key periodontal pathogens in vitro . In an experimental rat model of periodontitis, local administration significantly inhibits alveolar bone resorption and promotes functional tissue regeneration. Furthermore, to elucidate the underlying mechanisms of the composite system in alleviating periodontitis, we apply integrated transcriptomic and metabolomic profiling, which indicates a coordinated restoration of lipid metabolic homeostasis and mitochondrial energy metabolism. This multi-targeted strategy not only presents a promising therapeutic platform but also provides a mechanistic framework for the management of complex inflammatory conditions.