The concept of nanotechnology was touched upon by the concept “there’s plenty of room at the bottom”, a talk given by physicist Richard Feynman at an American Physical Society meeting at Caltech on December 29, 1959. The term ‘nanotechnology’ was first defined by Norio Taniguchi of the Tokyo Science University in 1974 [1]. Nanotechnology is on the verge of initiating extraordinary advances in biological and biomedical sciences that would be associated with both providing the tools for improved understanding of fundamental building blocks of materials and tissues at the nanoscale and designing technologies for probing, analysing and reconstructing them [2]. Nanotechnology or nanoscience refers to the research and development of an applied science at the atomic or molecular level (i.e. molecular engineering, manufacturing). Nanotechnology is applied to various medical fields like pharmacological research, clinical diagnosis, supplementing immune system, cryogenic storage of biological tissues. The growing interest in the dental applications of nanotechnology is leading to the emergence of a new field called Nano-dentistry [1]. Applications of such technology in dentistry and periodontics in particular, are no exception as periodontal destruction can be found to increase in prevalence with increasing age. The traditional clinical procedures of scaling, root planning and periodontal flap surgery, if followed by an adequate postoperative supportive periodontal care, results, in most cases, in successful management of progressive periodontal diseases. More recently, the regenerative treatment of periodontal defects with an agent or procedure, has attracted enormous interest from materials scientists and also from both private companies and government organizations because of its considerable economic potential and scientific significance. The necessary strategies for complete regeneration of human tissues should be the ultimate endpoint for the field of regenerative medicine and engineering. There has been significant progress made in recent years with the development and introduction of various metallic and polymeric materials structured in Nanoscales and the development of many biomaterials that form ideal interfaces with tissues. Using natural processes as a guide, substantial advances have been made at the interface of nanomaterials and biology, including the fabrication of nanofiber materials for three-dimensional cell culture and tissue engineering [3].

Advances in the Field of Periodontal Diagnosis

The use of nanotechnologies for diagnostic applications shows great promise to meet the rigorous demands of the clinical laboratory for sensitivity and cost-effectiveness. The use of nanodevices provides higher accuracy when performing diagnostic tests in the mouth by marking specific bacteria. Once marked, the bacteria can be easily identified and removed. Azzazy et al. [4] described nanodiagnostic tools such as quantum dots (QDs), gold nanoparticles and cantilevers, all of which showed a promising increased sensitivity, multiplexing capabilities. Quantum dots are beneficial in diagnosing oral cancer by, binding to cancer cells. Once they bind, UV light is radiated to them and starts UV light emission, making it easier to detect oral cancers. They can also be used as drug or gene carriers. Nathalia et al. described various diagnostic tools like nanopores that can detect carcinogenic molecules, nanotubes which are used for analysing dentin collagen network, dentin pores and their effects on tooth hypersensitivity, the surface of dental implants and colonies formed on tooth surfaces. Nanowire sensors can detect proteins or viruses in saliva samples. Nanosystems, such as the oral fluid nanosensor test, are effective in detection of salivary proteomic biomarkers and nucleic acids specific for oral cancer.

Whether nanodiagnostics will replace current diagnostic methods remains to be seen. Many aspects of these nanodiagnostic techniques need to be evaluated further, especially the safety issues.

Nanomaterials Used in Therapeutic Agents

Dentinal hypersensitivity is a common condition in patients with periodontal disease, which is even more pronounced after initial periodontal therapy. A wide range of commercially available products for the treatment of dentinal hypersensitivity are available. More recently, the toothpastes containing carbonated hydroxyapatite nanocrystals are being studied. These have high reactivity by which they bind to enamel and dentine apatite producing a biomimetic coating on enamel, contrasting plaque formation. They also prevent tooth from decay, rebuild and revitalize the teeth and seal dentinal tubules, annulling hypersensitivity. In near future new products of this kind will be a breakthrough in the treatment of dentinal hypersensitivity [5]. Dental nanorobots are able to move through teeth and surrounding tissues by using specific movement mechanisms. Nanocomputers that have been previously programmed via acoustic signals used for ultrasonography can control nanorobotic functions. Nanorobots known as dentifrobots, left by mouthwash or toothpaste on the occlusal surfaces of teeth can clean organic residues by moving throughout the supragingival and subgingival surfaces, continuously preventing the accumulation of calculus. Dentifrobots could also provide a continuous barrier to halitosis, since bacterial putrefaction is the central metabolic process involved in oral malodour [6].

Recently synthetic Carbonate hydroxyapatite (CHA) biomimetic nanocrystals similar to biogenic CHA nanocrystals have been shown to produce, In Vitro, re-mineralization of the altered enamel surfaces and closing of dentinal tubules, thus showing a potential use in desensitizing dentifrices. Hefferren et al. have suggested that, increased re-mineralization occurs more with apatite particles sizes <4μm. The potential desensitizing effect of biomimetic CHA nanocrystals, is due to the progressive closure of the tubular openings of the dentine with plugs within a few minutes until the regeneration of a mineralized layer has occurred within a few hours [5].

Seneviratne described a novel synthesis of mesoporous silica NPs encapsulated with pure (non-salt-form) chlorhexidine (CHX). They coated CHX on mesoporous silica NPs with inner pore channels of approximately 2.5 nm. The results obtained demonstrated that these CHX NPs had anti-bacterial effects against both planktonic and biofilm bacteria. Nano-CHX can act against several oral pathogens such as A. actinomycetemcomitans, E. faecalis, F. nucleatum, S. mutans and Streptococcus sobrinus (S. sobrinus) in planktonic modes and in mono-species biofilms, respectively. Moreover, CHX NPs can inhibit the growth of multi-species oral biofilm composed of S. sobrinus, P. gingivalis and F. nucleatum [7].

Nanotechnology Incorporated Regenerative Materials

Periodontal regeneration involves a set of complex tissues and structures in and around the tooth, hence, an ideal biomaterial-driven approach should include a functionally-graded scaffold where the chemical composition and 3D architecture can be achieved. Synthetic bioresorbable biomimetic hydroxyapatite nano and micro crystals exhibit excellent properties like bone filler biomaterial, such as biocompatibility, bioactivity, osteoconductivity, direct bonding to bone [8]. In a literature review on properties of nanocrystalline hydroxyapatite as a bone graft material in treatment of periodontal defects by Bayani et al. [9] reported that Nanohydroxyapatite can be considered a suitable alternative for autogenous bone graft in periodontal tissue regeneration.

Sowmya et al. [10] developed a 3-layer scaffold for the simultaneous regeneration of cementum, alveolar bone and periodontal ligament using nano-sized bioactive glass layer loaded with chitosan, cementum protein 1 (CEMP1), fibroblast growth factor 2 and nano-sized bioactive glass layer loaded with platelet-rich plasma (PRP) growth factors for bone regeneration. Histological and tomographic evaluations showed that the implantation of this scaffold in rabbits led to complete periodontal healing and new alveolar bone deposition. Zhang et al. [11] fabricated MBG/silk fibroin scaffolds incorporating BMP-7 and/or PDGF-B adenovirus and implanted them in dogs. These scaffolds loaded with PDGF-B were able to partially regenerate the periodontal ligament while those loaded with BMP-7 primarily improved new alveolar bone formation. Mota et al. [12] developed a combination of chitosan (CHT) with bioactive glass nanoparticles (BG-NPs) for bone regeneration in an in-vitro test. The results indicate that the CHT/BG-NP composite membrane could potentially be used as a temporary guided tissue regeneration membrane in periodontal regeneration, with the possibility to induce bone regeneration.

Nanomaterials in the Field of Implantology 

Dental implant has demonstrated clinical success over recent years despite its major problem due to implant fixation that leads to bacterial infection and rejection of the implant. Recently, nanomaterial coatings have been reported to have beneficial properties to improve implant fixation and increase the success rate. Nanoparticles are used as particle coatings on the implant surface that may increase the functionality and improve the stability and fixation of the implant. Coating of dental implants by osteoconductive nanomaterials could induce a chemical bond with bone and attain good biological fixation. Bone generation and regenerative potential of these materials can also provide a good condition [13]. Elemental Ag has been applied as an antimicrobial agent in many fields of medicine and Ag nanoparticles embedded in various film coatings have been applied to Ti implant surfaces to present antimicrobial activity. Zhang et al. [14] coated TiO2 implants by silver nanoparticle using Micro Arc Oxidation (MAO) method and the results showed enhanced antimicrobial effect resulted from interaction between the silver nanocrystals and the bacterial membrane. Their cell culture tests also indicated that the Ag-containing coatings possessed superior biocompatibility and non-cytotoxicity. Memarzadeh et al. tested a system containing mixtures of ZnO nanoparticles and nanohydroxyapatite as a coating material to reduce bacterial adhesion and support osteoblast growth. They found that ZnO can be considered as an optimal coating for implants in terms of both antimicrobial activity and biocompatibility [15].

Anu et al. [16] studied the Qualitative antibacterial activity of copper oxide nanoparticles coated titanium dental implants using Standard slurry dipping technique and wet chemical synthesis and this showed promising results against the entire varied test cultures used in the study. Quercitrin is a natural flavonoid with the ability to improve soft tissue integration and therefore, can increase dental implants success. Gomez-Florit et al. [17] tested the anti-inflammatory properties and potential of quercitrin-nanocoated titanium surfaces to improve soft tissue regeneration using human gingival fibroblasts. The anti-inflammatory results showed increased collagen mRNA levels, decreased matrix metalloproteinase-1/tissue inhibitor of metalloproteinanse-1 mRNA ratio and decreased pro-inflammatory prostaglandin E2 release under basal and inflammatory conditions.

Kim et al. [18] conducted an experiment for implant fixture surface modification. They prepared a sol containing TiO2 nanoparticles and coated it as a thin film on the implant surface using sol-gel method and found that the fixture treated with TiO2 nanoparticles leads to nontoxic and effective surface appearance and can induce initial bone formation after the implantation. The authors suggested that, to increase the uniformity of the coated TiO2 nanoparticles on the surface of the fixture and to enhance the adhesion of nanoparticles, anodic oxidation technique can be used as a complementary method together with the sol-gel method. Nanocrystalline diamond coatings with nano sized crystallites, has shown a great potential for different applications in biomedicine and biotechnology due to its high corrosion resistance and bio tolerance. Such a coating may be a selective protective barrier between the implant and the human environment. Metzler et al. [19] investigated the osseointegration of diamond-coated Ti-Al6-V4 dental implants after healing periods of 2 and 5 months in the frontal skull of eight adult domestic pigs. Their histomorphometry analyses showed the bone-to-implant contact and an adequate interface between the bone and the diamond surface.

Nanomaterials as Local Drug Delivery

Nanocomposite hydrogels are synthesized as model systems for in situ cured local drug delivery devices for the treatment of periodontal infections. Harungana madagascariensis leaf extract (HLE) investigated by Moulari et al. on oral bacterial strains used to treat gingival infections and dental caries, showed an improved antibacterial property and diminution of the bacterial concentration [20]. Dung et al. [21] used Antisense oligonucleotide-loaded chitosan tripolyphosphate (TPP) nanoparticles and showed the sustained release of oligonucleotides which is suitable for the local therapeutic application in periodontal diseases.

Herbal Nanomaterials for Periodontal Disease

Herbal medicines have been used worldwide for their better therapeutic values and fewer adverse effects as compared to modern medicines. Many herbal formulations have been produced for the treatment of oral diseases. Farjana et al. [22] and Zambrano et al. [23] found curcumin effective in preventing the activation of inflammatory mediators and its therapeutic effects on periodontal diseases. Curcumin Nano-curcumin capsules have a systemic target site with more bioavailability than topical forms. Malekzadeh et al. [24] studied the effects of oral nano-curcumin on gingival inflammation in patients with gingivitis and mild periodontitis and showed positive effects on the decrease of inflammation and gingival bleeding. Yang et al. [25] studied the antibacterial activities of silver nanoparticle composites made by pomegranate (Punica granatum) rind extract. The antibacterial experimental results indicated that when the concentration of Ag/Ag+/Ag3+ nanocomposites was 1.16 _ 10_4 mol/L, it had strong bacteriostatic action against gram positive and gram-negative bacteria.

The advent of nanotechnology in the field of dentistry has refined the traditional methods and helped in the development of advanced restorative materials and new medications. These approaches will continue to improve dental care. The advancement in periodontal diagnosis and treatment planning has developed immensely over the past few years. Nanotechnology has made the development of potent restorative nanomaterials possible and such materials can promote the growth of new bone structure in intrabony defect. Therapeutic agents could be loaded in carriers that can facilitate targeted, sustained and controlled release of the loaded drugs to the intended location. It is anticipated that the effectual and valuable relevance of the natural products and herbal remedies being applied with the nanocarrier will enhance the significance of existing drug delivery systems improving periodontal health. These nanotechnology-based drug carrier systems will play a vital role in future drug delivery systems for not only periodontal disease, but for a lot of other diseases of the oral cavity. However, the field of nanotechnology is still in its early stages. Extended investigations and research opportunities in this field may help advance dental therapeutics providing promising opportunities for the effective management of periodontitis.

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