Apical periodontitis is a biofilm-mediated disease; therefore, an antimicrobial approach is essential to cure or prevent its development. In the quest for efficient strategies to achieve this objective, antimicrobial photodynamic therapy (aPDT) has emerged as an alternative to classical endodontic irrigation solutions and antibiotics. The aim of the present critical review is to summarize the available evidence on photosensitizers (PSs) which has been confirmed in numerous studies from diverse areas combined with several antimicrobial strategies, as well as emerging options in order to optimize their properties and effects that might be translational and useful in the near future in basic endodontic research. Published data notably support the need for continuing the search for an ideal endodontic photosensitizer, that is, one which acts as an excellent antimicrobial agent without causing toxicity to the human host cells or presenting the risk of tooth discoloration. The current literature on experimental studies mainly relies on assessment of mixed disinfection protocols, combining approaches which are already available with aPDT as an adjunct therapy. In this review, several approaches concerning aPDT efficiency are appraised, such as the use of bacteriophages, biopolymers, drug and light delivery systems, efflux pump inhibitors, negative pressure systems, and peptides. The authors also analyzed their combination with other approaches for aPDT improvement, such as sonodynamic therapy. All of the aforementioned techniques have already been tested, and we highlight the biological challenges of each formulation, predicting that the collected information may encourage the development of other effective photoactive materials, in addition to being useful in endodontic basic research. Moreover, special attention is dedicated to studies on detailed conditions, aPDT features with a focus on PS enhancer strategies, and the respective final antimicrobial outcomes. From all the mentioned approaches, the two which are most widely discussed and which show the most promising outcomes for endodontic purposes are drug delivery systems (with strong development in nanoparticles) and PS solubilizers.
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