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Advancing Photodynamic Therapy for Endodontic Disinfection with Nanoparticles: Present Evidence and Upcoming Approaches

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Advancing Photodynamic Therapy for Endodontic Disinfection with Nanoparticles: Present Evidence and Upcoming Approaches applied sciences Review Advancing Photodynamic Therapy for Endodontic Disinfection with Nanoparticles: Present Evidence and Upcoming Approaches Rayyan A. Alfirdous 1,2, Isadora M. Garcia 3 , Abdulrahman A. Balhaddad 1,4 , Fabrício M. Collares 3 , Frederico C. Martinho 1,5 and Mary Anne S. Melo 1,6,* 1 Dental Biomedical Sciences Ph.D. Program, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; ralfi[email protected] (R.A.A.); [email protected] (A.A.B.); [email protected] (F.C.M.); [email protected] (M.A.S.M.) 2 Department of Restorative Dental Sciences, Prince Abdulrahman Advanced Dental Institute, Riyadh 11564, Saudi Arabia 3 Department of Dental Materials, School of Dentistry, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2492, Rio Branco, Porto Alegre 90035-003, RS, Brazil; [email protected] (I.M.G.); [email protected] (F.M.C.) 4 Department of Restorative Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia 5 Division of Endodontics, Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA 6 Division of Operative Dentistry, Department of General Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA * Correspondence: [email protected] Abstract: The persistence of microorganisms in the root canal system is one of the leading causes Citation: Alfirdous, R.A.; Garcia, of root canal treatment failure. Root canal anatomy is complex, and it is often a challenge to obtain I.M.; Balhaddad, A.A.; Collares, F.M.; optimal disinfection. Biofilms of putative pathogens hidden inside dentin tubules and other root Martinho, F.C.; Melo, M.A.S. canal ramifications may limit current disinfection protocols. The search for additional disinfection of Advancing Photodynamic Therapy the root canal has been intensely carried out over the last twenty years. Antimicrobial photodynamic for Endodontic Disinfection with therapy (aPDT) is an adjunctive, conservative, non-selective bacterial kill approach. aPDT has been Nanoparticles: Present Evidence and used to improve root canals disinfection without inducing bacterial resistance. This review focuses Upcoming Approaches. Appl. Sci. on the up-to-date aPDT performance and upcoming promising strategies for disinfection of the 2021, 11, 4759. https://doi.org/ 10.3390/app11114759 root canal system. First, we summarized the barriers encountered by photosensitizer (PS) and light delivery applied to root canal disinfection. Second, we compile the most updated clinical literature. A Academic Editor: Ivana Mileti´c systematic search for scientific articles was conducted in PubMed, MEDLINE, SCOPUS, and EMBASE to screen the related in vivo studies about this theme. Third, we summarized and critically analyzed Received: 21 April 2021 the current developments to overcome the aPDT limitations, and we revealed upcoming perspectives Accepted: 20 May 2021 in this scoping literature review. We present a timely and opportune review article focusing on the Published: 22 May 2021 significant potential of aPDT in endodontic disinfection. aPDT offers multiple capabilities that may be considered toward the root canal system’s disinfection with future outlooks in nanosized-platforms’ Publisher’s Note: MDPI stays neutral design and performance. with regard to jurisdictional claims in published maps and institutional affil- Keywords: infection control, dental; dental pulp diseases; photosensitizing agents; dental care; iations. microbiology; biofilms Copyright: © 2021 by the authors. 1. Introduction Licensee MDPI, Basel, Switzerland. Root canal infections are initially treated by removing the infected tissues and disinfecting This article is an open access article the root canal system with instrumentation and irrigation protocols. After that, clinicians distributed under the terms and perform an adequate root canal and apical sealing with the obturation and place an appropriate conditions of the Creative Commons Attribution (CC BY) license (https:// coronal sealing with a permanent restoration [1]. The root canal treatment usually saves the creativecommons.org/licenses/by/ tooth and clears the infection; however, endodontic treatment can still fail [2]. Different factors 4.0/). have been identified as contributors to endodontic treatment failure, such as untreated or Appl. Sci. 2021, 11, 4759. https://doi.org/10.3390/app11114759 https://www.mdpi.com/journal/applsci Appl. Sci. 2021, 11, x FOR PEER REVIEW 2 of 22 Appl. Sci. 2021, 11, 4759 usually saves the tooth and clears the infection; however, endodontic treatment can2 ofstill 20 fail [2]. Different factors have been identified as contributors to endodontic treatment fail- ure, such as untreated or inadequate filling of the canals. However, pathogenic biofilms’ persistenceinadequate fillingafter the of thestandard canals. disinfection However, pathogenic has been strongly biofilms’ attributed persistence to after endodontic the standard fail- uredisinfection and is known has been as one strongly of the attributed prime causes to endodontic of unsuccess failure [3]. The and presence is known of as biofilms one of the of putativeprime causes pathogens of unsuccess trapped [3]. inside The presence dentinal of tubules biofilms, its of ramifications putative pathogens and its trapped relation inside with thedentinal recurrence tubules, ofits clinical ramifications symptoms and and its relation presence with of theperiapical recurrence radiolucency of clinical symptomsis well re- portedand presence in the ofliterature periapical [4] radiolucency. The geometry is well of dentinal reported intubules the literature with a [narrow4]. The geometrylumen (1– of2 µm)dentinal and tubulesconsiderable with a length narrow (2 lumen–3 mm) (1–2 challengeµm) and the considerable disinfection. length Previous (2–3 mm) reports challenge have shownthe disinfection. bacterial Previousmigration reports into dentinal have shown tubules bacterial of the migration root at intoa depth dentinal of approximately tubules of the 360root– at420 a depthμm [5] of. approximately 360–420 µm [5]. In contrast, the irrigating solution, most commonly commonly,, sodium hypochlorite (NaOCl), has penetrability into dentinal tubules of approximately 130 µµm.m. Over and above, the quantificationquantification of penetration of the photosensitizer (PS) Toluidine Ortho Blue (TBO) into the dentin substrates via confocal Raman micro micro-spectroscopy-spectroscopy noted the maximum depth of penetration of 45 45–60–60 µµmm [[6]6].. As illustrated in Figure1 1,, using using confocal confocal laserlaser scanning scanning microscopy, viable bacterial cells of E. faecalis strain, labeled to show fluorescence fluorescence in blue, penetrate deep into the dentinal tubules.tubules. Figure 1. Representative confocalconfocal microscopic microscopic image image of ofEnterococcus Enterococcus faecalis faecaliscolonizing colonizing inside inside dentinal dentinal tubules tubules (20 ×(20×magnifi- mag- cation)nification) may may complicate complicate the the chemo-mechanical chemo-mechanical disinfection disinfection of root of root canal canal therapy. therapy. The root canalcanal systemsystem is is very very complex complex with with an an isthmus, isthmus, lateral lateral canals, canals, accessory accessory canals, ca- nals,and root and canalroot canal ramifications ramifications [7]. Such [7]. complexity Such complexity offersa offers challenge a challenge for optimal for optimal disinfection dis- infectionof the root of canalthe root system. canalThese system. areas These of isthmusareas of andisthmus ramifications and ramifications can harbor can putative harbor putativepathogens pathogens that may that evade may the evade antimicrobial the antimicrobial activity of activity conventional of conventional disinfection disinfe protocols,ction protocols,including instrumentationincluding instrumentation and irrigation and of irrigation the canals of withthe canals auxiliary with chemical auxiliary substances. chemical substances.Previous investigations Previous investigations have shown thathave conventional shown that rootconventional canal therapy root iscanal limited therapy to 44% is limitedto 70% ofto disinfection44% to 70% [ 6of,8 ].disinfection Moreover, studies,[6,8]. Moreover, using culture-dependent studies, using culture approaches,-dependent have approachesindicated bacterial, have in growthdicated after bacterial root canalgrowth disinfection after root completioncanal disinfection [9]. completion [9]. Limited putative putative pathogens pathogens can can survive survive in in the the root root canal canal system system with with the thelack lack of nu- of trientsnutrients after after the the endodontic endodontic treatment treatment [10] [10. E.]. E.faecalis faecalis is ais Gram a Gram-positive-positive bacterium bacterium that that is frequentlyis frequently recovered recovered from from persistent persistent endodontic endodontic infections infections [11] [11].. E.E. faecalis faecalis isis detected in 333%3% of persistent endodontic infections [[12]12].. This pathogen can be found as a monoculture monoculture in root canals with failed treatment [[13]13].. E. faecalis has unique characteristics to survive survive,, even after after disinfection. disinfection. This This pathogen pathogen can can penetrate penetrate the thedentinal dentinal tubules, tubules, persist persist in a low in a- nutrientlow-nutrient environment
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