Pathology‐Guided Cell Membrane‐Coated Polydopamine Nanoparticles for Efficient Multisynergistic Treatment of Periodontitis

Abstract Nanodrug delivery systems (NDDSs) for the treatment of periodontitis remain a significant clinical challenge. The low biocompatibility, singular effect, and lack of disease specificity of conventional nanoparticles limit their biomedical application. Recent studies have highlighted the pivotal role of cell membrane‐coated nanotechnology in anti‐inflammatory strategies due to its improved biocompatibility and superior biointerface properties. Herein, combined with the pathological heterogeneity of periodontitis revealed by bioinformatics analysis, this study develops a novel cell membrane‐coated nanoparticle composed of two elements: minocycline‐loaded polydopamine nanoparticles (PM) and cRGD‐modified cell membrane (RCM). The in vitro results indicate that PM@RCM rescues impaired human periodontal ligament stem cells through antioxidant, anti‐ferroptosis, anti‐inflammatory, and pro‐osteogenic effects, and exhibits favorable antibacterial bioactivity. The in vivo studies further reveal that PM@RCM promotes periodontal tissue regeneration and remodeled periodontal homeostasis in periodontitis mice. Collectively, these findings highlight the unique pathological changes in periodontitis. Moreover, the novel NDDS developed in this study, which leverages the excellent natural properties of cell membrane‐coated nanotechnology and the versatility of nanoparticle cores, provides a promising strategy for the clinical treatment of periodontitis.