In the era of the growing population, the demand for dental care is increasing at a fast pace for both older and younger people. One of the dental diseases that has attracted significant research is periodontitis. Periodontal therapy aims to regenerate tissues that are injured by periodontal disease. During recent decades, various pioneering strategies and products have been introduced for restoring or regeneration of periodontal deficiencies. One of these involves the regeneration of tissues under guidance using enamel matrix derivatives (EMDs) or combinations of these. EMDs are mainly comprised of amelogenins, which is one of the most common biological agents used in periodontics. Multiple studies have been reported regarding the role of EMD in periodontal tissue regeneration; however, the extensive mechanism remains elusive. The EMDs could promote periodontal regeneration mainly through inducing periodontal attachment during tooth formation. EMD mimics biological processes that occur during periodontal tissue growth. During root development, enamel matrix proteins are formed on the root surface by Hertwig’s epithelial root sheath cells, initiating the process of cementogenesis. This article reviews the challenges and recent advances in preclinical and clinical applications of EMDs in periodontal regeneration. Moreover, we discuss the current evidence on the mechanisms of action of EMDs in the regeneration of periodontal tissues.
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