The immune system is an extremely complex biological network that plays a crucial role in the hemostasis of periapical tissue, pathogenesis of apical periodontitis (AP) as well as periapical tissue healing. The successful elimination of microbial infections remains a significant challenge, mostly due to the ever-growing development of antimicrobial-resistant pathogens. The bacterial endurance in the root canal system contributes to features ranging from altered post-treatment healing to exacerbation of chronic periradicular immune response, that compromise the outcome of endodontic treatment. A highly effective strategy for combating infectious diseases and the associated inflammation-mediated tissue damage is to modulate the host immune response in conjunction with antimicrobial therapy. There are several medications currently used in endodontic treatment, however, they suffer various levels of microbial resistance and do not deliver all the required characteristics to simultaneously address both intracanal bacteria and periapical inflammation. Interaction of antimicrobial agents with the immune system can impact its function, leading to immune-suppressive or immune-stimulatory effects. The group of non-conventional antimicrobial medications, such as antimicrobial peptides, propolis, and nanomaterials, are agents that provide strong antimicrobial effectiveness and concomitant immunomodulatory and/or reparative effect, without any host tissue damages. Herein, we provide an overview of local immune modulation in AP and a comprehensive review of the immunomodulatory effect of antimicrobials intracanal medications applied in endodontics with specific emphasis on the antimicrobial nanomaterial-based approaches that provide immunomodulatory potential for successful clinical deployment in endodontics.Copyright © 2022. Published by Elsevier Inc.
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