Novel technologies to improve the treatment of endodontic microbial infections: Inputs from a drug delivery perspective

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Abstract

Endodontic microbial infections are still a challenge for an effective treatment for being biofilm-mediated and very refractory to conventional therapies. Biomechanical preparation and chemical irrigants cannot fully eradicate biofilms due to the anatomic structure of the root canal system. Instruments employed in biomechanical preparation and irrigants solution cannot reach the narrow and deepest portion of root canals, especially the apical thirds. In addition, aside from the dentin surface, biofilms can also infiltrate dentine tubules and periapical tissues, compromising treatment success. Therefore, different technologies have been investigated to achieve a more effective outcome in the control of endodontic infections. However, these technologies continue to face great difficulties in reaching the apical region and eradicating biofilms to avoid the recurrence of infection. Here, we present an overview of the fundamentals of endodontics infections and review technologies currently available for root canal treatment. We discuss them from a drug delivery perspective, highlighting each technology’s strength to envision the best use of these technologies.

Introduction

Endodontics is the science focused on preventing and treating dental pathological alterations of the pulp, the entire root canal system, and periapical tissues (Sadr et al., 2021) (Fig. 1). Root canal infections are the main endodontic problem experienced by many people that commonly occur due to exposure to biological agents, such as bacteria. These microorganisms can access the dental space through carious lesions, traumatic pulp exposition, and fractures, leading to a painful and difficult-to-treat inflammation (Dioguardi et al., 2019).

Conventional endodontic treatment, briefly described, is based on three pillars: (i) biomechanical preparation, with mechanical removal of microorganisms in the pulp, followed by (ii) root canal irrigation for microbial control employing intracanal antimicrobial drugs, and (iii) finalization, with complete obturation of the root canal system (Pereira et al., 2019). Although it may appear straightforward, endodontic treatment can be very challenging, mainly due to endodontic infections being polymicrobial (Neelakantan et al., 2017) and often mediated by microbial biofilms, which contribute to bacterial resistance mechanisms (Prada et al., 2019). Besides, root canal ramifications, dentinal tubules, and other anatomical irregularities inaccessible to endodontic instrumentation and intracanal substances (Pozos-Guillen et al., 2016) represent an additional difficulty for the treatment (Neelakantan et al., 2017), leading to persistent infections, which is prone to develop further complications, such as apical periodontitis (Siqueira et al., 2014). Therefore, microorganisms’ substantial reduction or elimination is crucial for the endodontic treatment success.

In this sense, technological research has been dedicated to improving the disinfection process during endodontic treatment, seeking higher effectiveness. Thus, various innovative approaches have focused on increasing the distribution capacity of these auxiliary substances irrigated through root canals (Borges et al., 2017).

Here, we briefly present the fundamentals of endodontics infections and review the current technologies available for root canal treatment, primarily targeting inaccessible areas for biomechanical preparation and discussing them from a Drug Delivery perspective. We further discuss each technology’s strength and the characteristics that still need improvement.

Section snippets

Pathogenic microorganism

Anaerobes and facultative anaerobes microorganisms dominate the microbiota of root canal system infections. Endodontic infections are classified into primary infection, which is characterized by dental pulp inflammation and root canal infection by microorganisms or microbial by-products, and secondary infection or post-treatment reinfection, which can occur as an emergent, persistent, or recurrent infection that re-develops in teeth after an apparent cure by a previous treatment (Neelakantan et

Conventional treatment

As mentioned above, the main objective of endodontic treatment is the complete eradication or significant decrease of microorganisms in the root canal system (Nagata et al., 2020) by killing microorganisms or making the environment unsuitable for microbiological growth. The basic steps of conventional treatment involve the biomechanical preparation, microbial control, and obturation of root canals (Pereira et al., 2019).

Technologies used to enhance endodontic disinfection

Along with the advancement of endodontic instruments, different techniques have been proposed to improve the disinfection process in the root canal system, promoting smear layers removal and increasing irrigant diffusion through areas not reached by mechanical instrumentation as the apical third of the canal system (Urban et al., 2017) and their ramifications (Pozos-Guillen et al., 2016). This section discusses the recent use of ultrasound, laser, photodynamic therapy, and iontophoresis.

Conclusions and prospects

Endodontic infections affect the root canal system causing pulp inflammation, and the treatment is based on partial or total pulp removal. In addition, these infections are mediated by a vast microflora, often forming biofilms in the complex root canal anatomy and dentinal tubules, representing a challenge for conventional treatment. With this in mind, using ancillary technologies is highly beneficial for antimicrobial endodontic treatment.

Such technologies apply physical resources to increase

CRediT authorship contribution statement

Thamires C. Miranda: Writing – original draft. Jayanaraian F.M. Andrade: Writing – original draft. Guilherme M. Gelfuso: Conceptualization, Writing – review & editing. Marcilio Cunha-Filho: Conceptualization, Writing – review & editing. Laudimar A. Oliveira: Writing – review & editing. Tais Gratieri: Conceptualization, Supervision, Writing – review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors acknowledge the Brazilian funding agency CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, Grant n. 402587/2021-9), the Federal District Research Support Foundation (FAP-DF, Brazil, grant n. 00193–00000746/2021-08, FAP-DF, Brazil, grant n. 00193-00000802/2021-04), and Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil).

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