CCL2-scavenging nanodecoy hydrogel multi-step remodel monocytes recruitment and macrophages polarization for periodontitis treatment

Periodontitis is a chronic inflammatory disease caused by pathogenic biofilms and over-activated host immune response, leading to sustained damage to periodontal supporting tissue and even tooth loss. A key therapeutic challenge in recurrence of periodontitis is persistent existence of infiltrating monocytes and macrophages in periodontal tissues. Particularly, C-C motif ligand 2 (CCL2) is vital for monocyte recruitment and macrophage polarization in periodontitis. In this study, we developed biomimetic caffeic acid phenethyl ester-loaded nanoparticles (M−CNPs) as nanodecoys by macrophage membrane encapsulation to block CCL2-mediated inflammatory response and tissue damage. M−CNPs were distributed in the thermosensitive gel matrix (M−CNPs@Gel) to improve the retention time and sustained-release in the periodontal pocket. Our study demonstrated that M−CNPs@Gel exhibited a significant nanodecoy effect by competitively binding to CCL2 in periodontium, which inhibited monocyte/macrophages recruitment. Additionally, biomimetic nanodecoy system could reprogram macrophages phenotype through multi-step blocking CCL-CCR2-PI3K pathway and ROS elimination. M−CNPs@Gel effectively reduced the infiltration of monocytes and macrophages, and promote alveolar bone regeneration by regulating the ratio of M1/M2 macrophages in vivo. This study develops a novel CCL2-scavenging biomimetic nanodecoy hydrogel that remodel monocytes recruitment and macrophages polarization for effective periodontitis treatment.