Peri-implantitis (PI) is a major cause of implant restoration failure, necessitating therapeutic strategies that integrate bone regeneration and anti-inflammatory effects. Despite advances in treatment, no existing agents simultaneously address both objectives. Exosomes (Exos), as key mediators of intercellular communication, have demonstrated dual anti-inflammatory and osteogenic capacities through microRNA (miRNA) delivery; however, their potential in PI therapy remains unexplored. This study evaluates the therapeutic efficacy of a composite hydrogel loaded with human umbilical cord blood-derived exosomes (UCB-Exos) in PI treatment, focusing on its dual anti-inflammatory and bone-regenerative functions, and elucidates the underlying molecular mechanisms.experiments revealed that UCB-Exos (30 μg/mL) enhanced the proliferation, migration, and osteogenic differentiation of BMSCs. Additionally, UCB-Exos suppressed pro-inflammatory cytokine expression (TNF-α and IL-1β) in RAW264.7 cells while upregulating anti-inflammatory IL-10. An nHAP-GelMA/AlgMA (nGA) composite hydrogel was developed, demonstrating a porous structure, excellent biocompatibility, and sustained UCB-Exos release., rat PI models were established to assess therapeutic outcomes. Micro-CT analysis following treatment with UCB-Exos-loaded nGA hydrogel showed significant PI bone regeneration, while H&E staining revealed reduced inflammatory cell infiltration. Furthermore, UCB-Exos could inhibit the expression of TNF-α and IL-1β and promote the expression of IL-10 in PI gingival tissues. High-throughput small RNA sequencing identified miR-182-5p as a key upregulated miRNA in the UCB-Exos group. Target gene prediction and dual-luciferase reporter assays confirmed that miR-182-5p directly targets the 3'UTR of MYD88. UCB-Exos, via miR-182-5p delivery, inhibited the MYD88/NF-κB signaling pathway, thereby promoting BMSCs osteogenic differentiation. These effects were reversed by miR-182-5p inhibitors. This study establishes UCB-Exos as a promising therapeutic agent for PI, demonstrating dual bone-regenerative and anti-inflammatory functions mediated by miR-182-5p inhibition of the MYD88/NF-κB pathway. These findings broaden the scope of UCB-Exos applications and offer a novel approach to the further development of medications for treating PI. In vitro In vivo
