Challenges and strategy in treatment with exosomes for cell-free-based tissue engineering in dentistry

In dentistry, problems of craniofacial, osteochondral, periodontal tissue, nerve, pulp or endodontics injuries, and osteoarthritis need regenerative therapy. The use of stem cells in dental tissue engineering pays a lot of increased attention, but there are challenges for its clinical applications. Therefore, cell-free-based tissue engineering using exosomes isolated from stem cells is regarded an alternative approach in regenerative dentistry. However, practical use of exosome is restricted by limited secretion capability of cells. For future regenerative treatment with exosomes, efficient strategies for large-scale clinical applications are being studied, including the use of ceramics-based scaffold to enhance exosome production and secretion which can resolve limited exosome secretory from the cells when compared with the existing methods available. Indeed, more research needs to be done on these strategies going forward. [GRAPHICS] Lay abstract: Application of stem cells in dental tissue engineering such as in osteochondral, periodontal, pulp, salivary gland or nerve regeneration as well as in osteoarthritis, mucosal, skin and oral wound healing, is still problematic, especially for its large clinical scales. Therefore, cell-free-based tissue engineering using exosomes isolated from stem cells is regarded next-generation treatment in dentistry. In this study, basic understanding on the exosomes, status, the potential for regenerative therapy including challenges and strategies for the clinical applications are reviewed. Future approaches to increase production and secretion from the cells are also proposed to resolve limitation in exosomes availability.