Understanding exosomes: Part 3-therapeutic + diagnostic potential in dentistry

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of various diseases. Over 5000 publications are currently being published on this topic yearly, many of which in the dental space. This extensive review article is the first scoping review aimed at summarizing all therapeutic uses of exosomes in regenerative dentistry. A total of 944 articles were identified as using exosomes in the dental field for either their regenerative/therapeutic potential or for diagnostic purposes derived from the oral cavity. In total, 113 research articles were selected for their regenerative potential (102 in vitro, 60 in vivo, 50 studies included both). Therapeutic exosomes were most commonly derived from dental pulps, periodontal ligament cells, gingival fibroblasts, stem cells from exfoliated deciduous teeth, and the apical papilla which have all been shown to facilitate the regenerative potential of a number of tissues including bone, cementum, the periodontal ligament, nerves, aid in orthodontic tooth movement, and relieve temporomandibular joint disorders, among others. Results demonstrate that the use of exosomes led to positive outcomes in 100% of studies. In the bone field, exosomes were found to perform equally as well or better than rhBMP2 while significantly reducing inflammation. Periodontitis animal models were treated with simple gingival injections of exosomes and benefits were even observed when the exosomes were administered intravenously. Exosomes are much more stable than growth factors and were shown to be far more resistant against degradation by periodontal pathogens found routinely in a periodontitis environment. Comparative studies in the field of periodontal regeneration found better outcomes for exosomes even when compared to their native parent stem cells. In total 47 diagnostic studies revealed a role for salivary/crevicular fluid exosomes for the diagnosis of birth defects, cardiovascular disease, diabetes, gingival recession detection, gingivitis, irritable bowel syndrome, neurodegenerative disease, oral lichen planus, oral squamous cell carcinoma, oropharyngeal cancer detection, orthodontic root resorption, pancreatic cancer, periodontitis, peri-implantitis, Sjögren syndrome, and various systemic diseases. Hence, we characterize the exosomes as possessing "remarkable" potential, serving as a valuable tool for clinicians with significant advantages.