Extracellular Vesicles as Orchestrators of Osteoimmunomodulation in Peri-Implantitis: Implications for Bone Regeneration

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction Peri-implantitis, characterized by inflammatory bone loss, is a leading cause of dental implant failure. Current regenerative strategies face limitations due to the persistent inflammatory microenvironment. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising acellular therapeutics with dual osteogenic and immunomodulatory capacities, offering a novel approach to address the complexity of peri-implant bone defects. Methods This narrative review synthesizes preclinical evidence on MSC-EVs for peri-implant bone regeneration. It examines methods for EV isolation from various sources. Furthermore, it analyzes advanced engineered delivery systems, such as peptide-functionalized implant surfaces and bioactive scaffolds, designed to enhance local retention and therapeutic efficacy. Results MSC-EVs orchestrate bone regeneration through multifaceted mechanisms. They directly stimulate osteogenesis by transferring pro-osteogenic miRNAs and proteins, activating key pathways like PI3K/AKT and Wnt/β-catenin. Crucially, they modulate the osteoimmune environment by reprogramming macrophages toward a reparative M2 phenotype, suppressing pro-inflammatory Th1/Th17 responses, and expanding regulatory T cells (Tregs). Concurrently, MSC-EVs inhibit bone resorption by favorably modulating the RANKL/OPG balance and directly interfering with osteoclast

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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