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Year : 2018  |  Volume : 8  |  Issue : 3  |  Page : 163-169

Clinical considerations of nanobiomaterials in endodontics: A systematic review

1 Ministry of Health, King Khalid Hospital, Alkharj, Saudi Arabia
2 Research Center, Riyadh Elm University, College of Dentistry, Riyadh, Saudi Arabia
3 Department of Restorative Dental Sciences, Riyadh Elm University, College of Dentistry, Riyadh, Saudi Arabia
4 Consultant in Prosthetic, Riyadh Elm University, College of Dentistry, Riyadh, Saudi Arabia

Date of Web Publication25-Jul-2018

Correspondence Address:
Dr. Mohammed S Alenazy
Ministry of Health, King Khalid Hospital (Kharj), P.O. Box 21437, Riyadh 11475
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sej.sej_67_16

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Introduction: Clinical dentistry and primary oral care continue to experience significant improvements in quality at different levels of dentistry. These changes and improvements are of great benefit to both patients and clinicians because of significant achievements and advances in the physical, chemical, and biological sciences. Nanotechnology and its varied products are eloquent examples of these revolutionary trajectories in scientific discoveries and endeavors. Scientific revolution of nanotechnology has afforded the dental profession with a wealth of novel nanobiomaterials, templates for dental tissues regeneration, oral fluid nanodiagnostics, and the potential ability to use nanoparticles to replace lost dental hard tissues.
Materials and Methods: A manual and systematic electronic search was conducted using the PubMed database. Several keywords were used: “nanocharacterization” “nanoclinical applications” “endodontics” “nanodentistry” “nanotechnology (263) (278) papers were excluded because they were duplicated papers,” “nanoparticles” and “regeneration.” Relevant articles published up to 2016 in the English language were retrieved.
Results: Initial electronic and manual searches identified (571) studies. Preliminary analysis was performed on a total of (332) publication by screening titles and abstracts of articles. A second phase, data studies, or unrelated reports were excluded. Full texts of the remaining (54) papers were retrieved. A manual search added (6) publications on the topic to give a total of (60) publications, literature reviews, which were included in this review.
Conclusions: Physical and chemical improvements in nanotechnology products continue to occur and may soon lead to the development of “smart” endodontic therapeutic agents and materials. The future looks auspicious for sustained dramatic inventions in novel nanomaterials for clinical dental applications.

Keywords: Endodontics, nanobiomaterials, nanotechnology, regeneration, sealer

How to cite this article:
Alenazy MS, Mosadomi HA, Al-Nazhan S, Rayyan MR. Clinical considerations of nanobiomaterials in endodontics: A systematic review. Saudi Endod J 2018;8:163-9

How to cite this URL:
Alenazy MS, Mosadomi HA, Al-Nazhan S, Rayyan MR. Clinical considerations of nanobiomaterials in endodontics: A systematic review. Saudi Endod J [serial online] 2018 [cited 2019 May 19];8:163-9. Available from: http://www.saudiendodj.com/text.asp?2018/8/3/163/237560

  Introduction Top

Over 60 years ago when the American Nobel Laureate physicist Richard Feynman [1] conceptualized the potential applications of “nanotechnology,” most likely he did not imagine the varied applications of nanotechnology that today pervade nearly all spheres of human activities. The concept, which evolved from Newton to Bernoulli, Dalton, Maxwell, Boltzmann, Rutherford and many other great minds, and the concept of atoms and molecules became real and researchable. In the process, small measurements in the order of angstrom, nanometers, and femtometers became realities that could be applied to linear and volumetric determinations.[2]

Nanotechnology and its products (i.e., applications) impact our everyday lives today. It involves the development of several materials and devices as well as systems exhibiting properties different from those of larger scale.

Descriptive new terminologies within the general field of nanotechnology have emerged: nanoparticles, nanowires, nanotubes, nanoshells, nanospheres, nanocapsules dendrimers, nanoassemblers, and many others.[2] Nanoparticles are microscopic particles with dimensions ranged from 1 to 100 nm. Between 2000 and 2014, over 60 published articles appeared in peer-reviewed journals describing the varied applications of nanotechnology and its products in all areas of dental and oral care.

Robert Freitas has been credited with announcing the new and emerging field of nanomedicine in 1993.[2] Nanomedicine may be defined the diagnosis, treatment, and prevention of diseases in health sciences with nanosized particles in various forms. New words in disease management have since entered drug usage, namely “nanoscaffolds” for tissue regeneration and “nanorobotics” for both diagnosis and therapy.[3] Dentistry, dental care, and dental biomaterials are beneficiaries or products of what may be called the “ocean” of nanotechnology that literally manipulates molecules and atoms to create new products, structures, and services.[4]

Despite the accumulation of knowledge of nanotechnology in relation to dental materials, the application of nanobiomaterials in endodontics needs to be highlighted. This systematic review will focus on the possible application of nanotechnology and nanobiomaterials in endodontics scientific topics.

  Materials and Methods Top

A literature review was performed to determine the potential uses of nanotechnology in endodontic treatments. The review was conducted using the PubMed database, a search engine mainly accessing the MEDLINE database of references. Several keywords were used: “nanocharacterization,” “nanoclinical applications,” “endodontics,” “nanodentistry,” “nanotechnology,” “nanoparticles,” and “regeneration.” Relevant articles published up to 2016 in English language were retrieved.

  Results Top

A total of 571 studies were initially identified. A preliminary total of 332 publications were included, and their titles and abstracts were screened. During the second phase, 263 (278) were excluded because they were duplicated papers, literature reviews, data studies, or unrelated reports. The full texts of the remaining 54 papers were retrieved. A manual search led to the discovery of six additional publications on the topic to give a total of 60 publications [Figure 1]. The publications were categorized according to the followings:
Figure 1: Data flowchart

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Nanotechnology in endodontics

Endodontic treatment over time has become a highly predictable procedure, reported to have more than 96% success rates in the absence of preexisting apical periodontitis.[5] Biomechanical steps, disinfection, and three-dimensional sealing and obturation of the root canal system are essential procedures in the success of endodontic treatment.[6] Despite the established high success rate of root canal treatment, failure still occurs due to the inadequacy of the biomechanical step of the complex anatomical canal system and/or microleakage of the sealing material. This microleakage most likely occurs because of quality deficiencies.[7],[8] Recent endodontic materials have particular limitations of shrinkage, dissolution in oral environment, and sensitivity to moisture.[9] Predictably, the development of suitable materials that have superior biomechanical and sealing properties for root canal systems is ensuring the longevity of endodontic treatment success.

A new era of nanomaterials studies has resulted in material development that improves clinical outcomes. A simple definition of nanotechnology is the “creation of functional materials with structures sized, 100 nm, or smaller.”[10] The field of endodontology has a considerable number of ongoing research activities that are attempting to improve several clinical management aspects such as files and filling materials. Some nanoparticles possess antimicrobial properties that might enhance the efficacy of endodontic materials, irrigation solutions, and intracanal medicaments because of their minute size and ability to spread into complex anatomical areas in root canal systems [11],[12] as shown in [Table 1].
Table 1: Numerous studies for different nanomaterial and their proposed application

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The majority of efforts have continuously focused on creating “nanomodified” materials. The spreading of these particles in recent and novel materials could strengthen the sealability of obturation and sealer materials, which are used either in root-repair and/or root-end filling materials.[12],[22]

Nanoapplications in endodontics instruments

Nickel-titanium (NiTi) endodontic rotary files are one of the most commonly used instruments in endodontic regular daily dental practice. These types of alloys have numerous favorable characteristics including high corrosion resistance and superelasticity which endows them with excellent shape memory. This type of rotary file makes it possible to explore the complex anatomy of a root canal to ensure appropriate endodontic treatment.[23],[24]

Cobalt coatings of the NiTi file with impregnated fullerene-like WS2 nanoparticles cause a significant improvement in the fatigue resistance and breakage time.

Nanoenhancement of the canal disinfection material

Various medical solutions are used for sterilizing root canal spaces, and these solutions are generally categorized as either irrigants or medicaments. Clinically, the usage of irrigants is often conducted in a significantly higher volume than medicaments. In addition, irrigants require longer contact times inside canal walls, and medicaments have to be applied over a longer period to achieve efficacy at disinfecting the canal system. The incorporation of nanoparticles has been proposed for irrigants and medications to enhance their ability at sealing and disinfecting the entire root canal system.

Endodontic canal irrigants

Eradication and disruption of microbial biofilms within the root canal space are the objectives behind implementing the biomechanical step. Despite emphasis being placed on the mechanical instrumentation of root canals, irrigants have been shown to play a key role in the disinfecting process within the canal system.[25] This property of disinfection is very important in complex canal anatomy systems (e.g., fins and the isthmuses) that cannot be easily cleaned or are easily missed by instrumentation alone.[26]

A fundamental concern with regard to irrigating fluids and their techniques is the ability to reach all regions of the canal spaces and remove debris such as the smear layer and biofilms without causing harm to normal tissues. Several types of irrigants and techniques are generally used manually or mechanically when disinfecting a root canal system. Recent reports have explored using nanoparticle-type irrigants to improve the cleaning of root canal systems; these studies have also focused on tissue responses to the use of such irrigants.[27] One of the materials that had been used over the last decade is silver nanoparticles. These nanoparticles have been used in different applications as an antibacterial and antifungal agent and as a component of biotechnology and bioengineering in dental care.[10],[28] A study using an animal model reported that animal tissue tolerated a sponge embedded with either 47 or 23 ppm sliver nanoparticles as dispersion material filled in polyethylene tube better than control animals tissue with a plain fibrin sponge embedded with 2.5% sodium hypochlorite over 3 months.[29] The authors concluded that a 23 ppm concentration of silver nanoparticle dispersion material was more biocompatible with tissue compared with other materials. Then, a concern about health issues was raised. After reviews of the toxicological effects of exposure to silver nanoparticles, it was reported that these nanoparticles might be linked to several problems with “inflammatory, oxidative, genotoxic, and cytotoxic consequences.”[30] Additional clinical trials studies were justified to confirm the safe utilization of these nanoparticles in both filed medical and dental applications. An alternative method of disinfecting root canal spaces, which is called nanoparticle-based antimicrobial photodynamic therapy, has been investigated with promising preliminary findings. In an in vitro study by Pagonis et al., the effectiveness of polyacticcoglycolic acid (PLGA) nanoparticles synergized with light against Enterococcus faecalis was assessed using transmission electron microscopy and photosensitizer methylene blue (MB).[13] These authors found that the nanoparticle component acted generally on microorganism's cell walls causing a significant reduction in the number of colony-forming units in the culture. They concluded that the use of PLGA nanoparticles encapsulated with protective drugs might be a promising step in antimicrobial root canal treatment. Another comparative study showed that the cationic photosensitizer had the ability to deactivate the content of microbial biofilm bacteria such as E. faecalis and worked to disrupt the structure of biofilm.[31] These nanoparticle-based disinfections may become important additions to the currently available conventional irrigants used in endodontic treatment.

Root canal sealers

The sealer enhances the conceivable achievement of an impervious seal and serves as filler for canal irregularities and minor discrepancies between the root canal spaces and the obturation material (e.g., gutta-percha). Sealers frequently get into accessory or lateral canals, and they can help with microbial control in case that there are microorganisms remaining in dentinal tubules.[32],[33] Sealers can likewise serve as lubricants to aid in the sealing of the obturation core-filling material in the thorough compaction. Inside root canals where the smear layer has been removed, numerous types of sealers exhibit expanded adhesive features to dentin tubules.[34],[35] Since the small size of nanoparticles ensures that they can penetrate dentinal tubules to seal all spaces effectively, the development of a sealer based on nanotechnology may be an important step to achieve a better sealer material in endodontics. Investigators have studied nanohydroxyapatite (NHA) crystals (279 nm) as the primary composition of new biotype root canal filling sealers based on calcium phosphate cement on extracted teeth.[36] This sealer exhibited stronger antimicrobial properties against Actinomyces naeslundii, Porphyromonas gingivalis, Porphyromonas endodontalis and Fusobacterium nucleatum than regular sealers. In addition, it demonstrated insignificant microleakage compared with different materials. In another preliminary study, nanocrystalline tetracalcium phosphate had essentially a higher antimicrobial strength in an agar-diffusion test.[14] The development of amorphous calcium hydroxide during setting was thought to increase the pH level in the agar gel around the examples yielding a zone of restraint. Others materials, available in the market-containing nanosize particles, include Mineral Trioxide Aggregate (MTA-Fillapex), iRoot SP, and EndoSequence BC root repair material. These materials are biocompatible, antimicrobial, and possess biomineralization.[22] In addition, they demonstrated a moderate toxicity that diminished over the time when completely set.[37]

Retrofilling and root-repair materials

Various studies have described the importance of retrograde root filling placement during periapical surgery such as MTA and EndoSequence BC root repair materiel putty. Wu et al.[38] recommended that a tight and durable seal of retrograde root fillings is of essential clinical importance. A few studies have shown that, in the absence of an acceptable root canal filling, surgical treatment can be compromised.[39] Moreover, various clinical studies pertaining to healing quality after periradicular surgery have affirmed the advantage of doing acceptable root canal filling before surgery.[40] MTA has become the material of choice for retrograde fillings despite its drawbacks of long handling and setting times. To remove these drawbacks, a recent study by Saghiri et al.[15] assessed a nanomodified MTA for upgraded physiochemical properties. They found that there was an increase in the surface area of the MTA powder with the addition of nanodispersion, which decreased the setting time and enhanced the microhardness of the material. This modification apparently aided the MTA in setting faster but compromised the required hardness once it was completely set. Other researchers are investigating and exploring new materials as opposed to adjusting current materials. The term polymer nanocomposite (PNC) is generally used for all polymeric materials that are loaded with a minimum amount of nanoparticles such as clays and carbon nanotubes compared with conventional composites.[41] The dispersed phase has a high surface-to-volume proportion. PNCs have therefore demonstrated significantly enhanced mechanical and thermal properties, even at very low content of fillers in the range of 0%–5%. The previous studies have demonstrated considerable enhancements in resistance to heat,[41] dimensional stability,[42] stiffness,[43] reduced electrical conductivity [44] and most remarkably, drug elution abilities.[45] Recently, two such novel nanocomposites polymer (NERP1 and NERP2) were examined for initial apical seal alongside a regularly used polymer-based compomer in an in vitro study model.[16] They found that NERP1 can reduce apical microleakage significantly. Modareszadeh et al. assessed the bioactivity values and cytotoxicity of two forms of novel root-end filling materials, PNC resins (C-18 amine montmorillonite [MMT] and vinylbenzyl-octadecyldimethylammonium chloride MMT) compared to ProRoot_ MTA and Geristore. Their results demonstrated no significant difference in cytotoxicity among ProRoots MTA, Geristores and PNC resin C-18 at all time intervals.[17]

Nanoapplications for repair and pulp regeneration

The primary concern of researchers and clinicians in dental tissues studies is to achieve total recovery of dental pulp tissues. In endodontology, repair and regeneration are concerned with systems and mechanisms involved in maintaining or restoring the original structures and functions by manipulating the embryonic stem cell development process. In the human body, there are several low-compliance systems, of which dental pulp is considered to be an example due to its enclosure between rigid encasement walls. An alterations in capillary filtration, such as in inflammation, can have dramatic effects. Therefore, it is difficult to access dental pulp without creating an inflammatory reaction. From this point of view, probable repair and/or regeneration of injured, inflamed or necrotic dental pulp must be preceded by an understanding of the nature of this action. An unusual attribute of dental pulp is that it has completely sensory tissue. Human pulp has several unusual features such as terminal microvascular supplies, few anastomoses, and a generally large volume of tissue with generally little vascular supply.[46] The types of vessels that enter and exit pulp tissue are arterioles and venules. Finally, the most likely significant obstacle to repair and regeneration in responding to pulp stress is that the pulp is enclosed by a hard tissues of dentin, enamel (crown), and cementum (root).[47] However, despite the surrounding environment of dental pulp, it possesses a considerable ability to repair itself.

The principal cause of pulpal reactions to stresses is the onset of dental caries. When it progress, pulpal inflammatory reaction is elicited, and as it gets deeper inside the enamel and dentin, the microorganism and their toxic products reach directly into pulp tissue. When the cause (caries) is removed at an early stage, the damage and the inflammation of the pulpal tissue will normally be resolved. Recently, investigations have shown that repair and regeneration can occur in a low-compliance system such as dental pulp.[47] Several studies have been carried out in animal models with dentition similar to humans.[48] The ultimate aim of these studies has always been to grow a natural tooth, including its soft and hard tissues, to replace a missing tooth. The technology is now available for this growth to be achieved in the not-so-distant future.

In recent studies, concern has been expressed about the application of results from animal models to humans in the area of tissue regeneration. The complexity of efforts is related to the components of stem and progenitor cell proliferation,[49] differentiation development,[50] scaffold types,[51] the regeneration of neural and vascular tissues,[52] and mechanisms of signaling and the proteins that are involved in the process of signaling.[53]

An investigation was conducted to test the microleakage of five bonding systems using nanoparticles of silver ammoniacal nitrate. The findings were evaluated under an SEM in emission environment in a backscattered electron mode of an yttrium aluminum garnet laser. Detection of the probable existence of silver particles was conducted using an electron dispersive system analysis in parallel. Three types of restorative systems indicated clear silver uptake in the adhesive and hybrid layers.[54] A recent study by Fioretti and his group tested the toxicity of nanostructured assemblies on the dental pulp tissues. Anti-inflammatory properties were demonstrated through alpha-melanocyte-stimulating hormone (MSH). The combination of substances polyglutamic acid-alpha-MSH decreased the amount of lipopolysaccharide caused the proliferation of fibroblast cells. Although the mechanism of action of this substance is not clear yet, it may play an important regulatory function in modulating pulpal inflammation.[18] Another study used caffeic acid phenyl ester, which prevented the endogenous matrix metalloproteinases that cause hybrid layer degradation.[55] The completion of maturation all through the crown and roots occurs through the continuous process of mineralization.

An odontoblast is a nondividing cell that functions over the lifetime of dental pulp. If it is succeeded by a cell, it is called an odontoblast-like cell in the case of infection or injury.

Secondary dentin forms due to physiological processes during the lifetime of a tooth from activities of the original odontoblastic layer by the same mechanism that produced the primary dentin. Both primary and secondary dentin have tubules.[56] Odontoblast-like cells are presumed to give rise to a form of a dentin-like structure.[57] Nanostructured polymer scaffolds had been developed and examined by Smith et al. for regeneration and bioengineering.[58] The investigation concentrated on nanofibrous (NF) scaffolds with combinations of components. This material is composed of extracellular matrices (ECM), the dimension of which range between 50 and 500 nm. A polymer with biodegradable properties is then cast through the scaffold porosity to form NF with nanofibers that have the same diameter as the ECM. In NF and composite control scaffolds, the ability of the cell to adhere, proliferate, and differentiate is improved.[58]

The production of an engineered replica of the naturally occurring ECM can promote new tissue development. This achievement is a significant step forward in understanding the improved biological regulation of cell behavior for tissue repair and regeneration.[58] One study has assessed the behavior of dental pulp stem cells (DPSCs) on different scaffolds such as NF/gelatin/nano-hydroxyapatite NHA. A seeding process of DPSCs was initiated on electrospun poly/gelatin scaffolds either with or without NHA. Different tests were conducted that analyzed the in vitro DNA content, the movement of alkaline phosphatase, and measurements of osteocalcin, which demonstrated that the scaffolds supported the adhesion of DPSCs, proliferation, and differentiation of odontoblasts. The two types of scaffolds were seeded with DPSCs that were embedded subcutaneously into immunocompromised nude mice. The control group contained scaffolds with NHA but without DPSCs. The results of the study demonstrated that the combination of NHA on scaffolds upregulated a specific expression of odontogenic gene, and then, NHAs with nanofibers enhanced the differentiation of DPSC to be odontoblast-like cells phenotypically in both in vitro and in vivo study models.[59]

One study assessed the differentiation of human odontogenic DPSCs on NF poly L-lactic acid (PLLA) scaffolds.[60] Another study used highly permeable scaffolds of NF-PLLA that mimicked collagen type-I fibers with and without the usage of growth factors “Bone Morphogenic Protein-7 (BMP-7)” and dexamethasone (DXM) medium. The mixing of the growth factor BMP-7 and DXM stimulated the differentiation of odontogenic DPSCs more effectively than DXM alone. Finally, the environment that was provided by the nanoscaffolds was excellent support for DPSCs in regenerating dental pulp, dentin, and enamel.[21]

  Conclusions Top

The cumulative literature data have indicated that the importance of nanotechnology revolution on endodontics practice is yet to be realized. Nanotechnology applications are relevant to root canal therapy in several aspects, namely, canal irrigation, instrumentation, obturation, canal sealers, pulp repair, and/or endodontic regeneration therapy. Physical and chemical improvements in nanotechnology products continue to occur and may soon lead to the development of “smart” endodontic therapeutic agents and materials. The future looks very promising for dramatic nanoenhancement in inventing novel materials in all aspects.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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