Table 2.

Characteristics of studies conducted on the application of EVs for periodontal regeneration

Origin/source	Study mode	Active EV cargo molecules	Key function/targeted genes	References
MSCs-EVs	In vitro and in vivo (rat periodontal defect model)	–	Improved periodontal ligament function and promoted regeneration/initiation of prosurvival AKT and ERK signaling in PDL cells/enhanced cell viability	[178]
ADSCs-EVs	In vivo (rat ligature model)	–	Improved periodontal repair and regeneration	[179]
Mobilized-DPSCs-CM	In vitro	–	Greater proliferation and migratory activity of NIH3T3 cells/higher immunomodulatory effects/decreased apoptosis	[180]
PDLSCs-CM	In vivo (rat periodontal defect model)	SerpinE1, MCP-1, TIMP-1, uPA, VEGF, IGFBP6, IGFBP2, PDGFR-β, and IFN-ɣ	Enhanced periodontal regeneration by suppressing the inflammatory response via decrease in TNF-α	[93]
MSCs-CM	In vitro and in vivo (rat periodontal defect model)	IGF-1, VEGF, TGF-β1, HGF	Increased wound-healing and angiogenesis/up-regulation of osteogenetic- and angiogenic-related genes expression/induced periodontal tissue regeneration	[181]
GMSCs-CM PDLSCs-CM	In vitro and in vivo (rat periodontal defect model)	–	Promoted periodontal defect regeneration/lower expression levels of TNF-α and IL-1β/higher IL-10 expression/higher expression levels of BSP-II and Runx2	[182]