Periodontal therapy is aimed at regenerating oral tissue injured by chronic, inflammatory periodontal disease. During the current era, various treatment protocols, strategies and products have been introduced for new regeneration of periodontal deficiencies. One of these involves the regeneration of tissues under guidance using enamel matrix derivatives (EMDs) or combinations of these. EMDs being mainly comprised of amelogenins, is the most common biological agents used in periodontics. Multiple studies have been reported the role of EMD in periodontal tissue regeneration; however, the extensive mechanism remains elusive. EMDs could promote periodontal regeneration mainly through inducing periodontal attachment during tooth formation. 

EMD are also said to mimic the 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 tried to review and enumerate the challenges and recent advances in preclinical and clinical applications of EMDs in periodontal regeneration. The current evidence on the mechanisms of action of EMDs in the regeneration of periodontal tissues is also mentioned here. 

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