Synergistic potentials of small extracellular vesicles, biomaterials, and 3D bioprinting in periodontal regeneration: a scoping review

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• 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)

Periodontitis is a chronic inflammatory disease characterized by the progressive destruction of both soft (gingiva and periodontal ligament) and hard (cementum and alveolar bone) supporting tissues. The complex periodontal microenvironment often limits the effectiveness of current clinical treatments in achieving functional tissue regeneration. Although mesenchymal and immune cell-based therapies hold promise, concerns related to cell viability and immune compatibility limit their clinical translation. As a natural secretome, small extracellular vesicles (sEVs) are cell-secreted nanoparticles that deliver bioactive molecules for cell-to-cell communication to modulate immune response and promote tissue regeneration. To assess the translational readiness of sEVs therapy, this scoping review first outlines the current clinical trials of mesenchymal stem cells (MSCs)-sEVs in periodontitis, followed by a transition to preclinical application of integrating sEVs with biomaterial scaffolds to enhance localized regenerative outcomes. We then analyzed eight preclinical studies utilizing 3D bioprinted MSCs-sEVs/human umbilical vein endothelial cells-sEVs (or immune cell-derived sEVs) constructs in bone and vasculature regeneration models, and one study related to in vitro periodontal regeneration. These constructs exhibited improved outcomes in osteogenesis, angiogenesis, and immunomodul

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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