|Year : 2015 | Volume
| Issue : 2 | Page : 86-90
Nanotechnology: An upcoming frontier in implant dentistry
Dipti Khullar, Nidhi Duggal, Sarabjit Kaur
Department of Prosthodontics and Crown and Bridge Work, GDC Patiala, Patiala, Punjab, India
|Date of Web Publication||2-Mar-2016|
142 Urban Estate, Kapurthala - 144 601, Punjab
Source of Support: None, Conflict of Interest: None
Osseointegration, i.e., structural and functional union of the surface of dental implant with surrounding bone is paramount for the success of device. In recent years, osteogenesis at the bone-implant interface has been induced by structural modifications of the implant surface, particularly at the nanoscale level. This has been achieved through modulation of osteoblast adhesion. There is strong belief that nanoscale features in materials processing is truly a new frontier. This paper reviews recent advances in fabrication of novel coatings and nanopatterning of dental implants and their subsequent cellular interactions, leading to an improvement in osseointegration and hence the long-term clinical success of the "third dentition" i.e., dental implants.
Keywords: Mesenchymal stem cells, nanopatterning, nanotechnology, implants
|How to cite this article:|
Khullar D, Duggal N, Kaur S. Nanotechnology: An upcoming frontier in implant dentistry. Saint Int Dent J 2015;1:86-90
Implant dentistry has undergone a slow and steady growth in the last 30 years. When the idea of osseointegration first emerged in the late 1970s, , nobody thought dental implants would have real breakthrough over the years.
The macroscopic level deals with the screw design, thread shape, and pitch distance while microscopic level deals with coating of the implant surface. Microscale features create a microenvironment that can modulate cells recruitment and function.  Roughness of surface can influence osseointegration using cell attraction, improving cells adhesion.
Nanotechnology is defined as the creation of functional materials, devices and systems through the control of matter on the nanometer scale (1-100 nm).  First promising avenue is through surface engineering that would include nanoscale topography and coatings for better and faster osseointegration of implants.
| Nanolevel Surface Modifications|| |
New coating technologies have been developed for applying hydroxyapatite (HA) and related calcium phosphates (CaP), onto the surface of implants. These CaP coatings provide titanium implants with osteoconductive surface. , Dissolution of CaP coatings in peri-implant region increased saturation of blood leading to precipitation of biological apatite nanocrystals onto surface of implants which incorporates proteins and promotes adhesion of osteoprogenitor cells that would produce extracellular matrix of bone tissue. Furthermore, it is seen that osteoclasts, bone resorbing cells, can degrade CaP coatings through enzymatic ways and create resorption pits on coated surface. , Presence of CaP coatings on metals promotes early osseointegration of implants with direct bone bonding as compared to noncoated surfaces. Challenge is to produce CaP coatings that would dissolve at similar rate than bone apposition to get direct bone contact on implant surfaces.
Idea is to apply thin ceramic layer that will bond both to the implant and to the surrounding tissues and promote bone apposition. Candidate coating materials are bioactive compounds that can promote cell attachment, differentiation, and bone formation.  When implanted, these bioactive ceramics form hydroxyl carbonated apatite on their surface through dissolution and precipitation.  This phase is equivalent in composition and structure to mineral phase of osseou tissue. ,,,
Benefits during healing and bone remodeling processes , include faster healing time,  enhanced bone formation, , firmer implant-bone attachment,  and reduction of metallic ion release.
Essential requirements of new family of coatings include (a) Strong adhesion to implant (b) good fixation to bone (c) their microstructure and dissolution rates programed to match in vivo healing processes (d) act as templates for in situ delivery of drugs and growth factors. 
Plasma spray [Figure 1] creates nanostructure, with features standing below 100 nm. The process enables wide range of materials (e.g., Ag, Au, Ti) to be coated on many underlying materials (metals, polymers and ceramics). Nanoparticulate coating with Ti particles has been demonstrated to increase osteoblast density on implant surface. Reising detected greater deposition of calcium on nano Ti-coated surfaces [Figure 2] as compared to uncoated surfaces. 
Plasma spraying of HA offers little control over coating thickness and composition. High processing temperature causes partial thermal decomposition of HA resulting in coatings with unacceptable heterogenous properties. Causes of failure of HA-coated implants include unreliable adhesion, continued dissolution of coating,  poor control of physicochemical properties and hence biological stability of coating. 
Use of bioactive glass in coating
Bioglass enhances adhesion of implant to bone [Figure 3]. There is a possibility of creating layers with finely tuned properties. Reverse transcription-polymerase chain reaction analysis showed silicate glass coating induced two-fold expression of RunX-2, key marker of osteoblast differentiation, compared to Ti6Al4V. 
Anodization [Figure 4] creates nanostructures with diameters >100 nm on titanium implants. Voltage and direct current (galvanic current) are used to thicken oxide layer among implant surface. Ti substrates serve as anode while inert platinum sheet serves the cathode and are submerged in electrolyte solution of diluted hydrogen fluoride. Subsequently, strong acid dissolves oxide layer creating a pattern that follows convective lines of galvanic current. 
Combination of acids (bases) and oxidants
The combination of strong acid is effective in creating thin grid of nanopits on titanium surface (diameter 20-100 nm). Treatment with H 2 SO 4 -H 2 O 2 on Ti implants create nanopattern associated with enhanced osteogenesis. Vetrone  confirmed promotion of stem cells growth by oxidative nanopatterning [Figure 5].
Blasting [Figure 6] creates porous layer on implant surface through collision with microscopic particles. Rough surface obtained enhances bone formation and osseointegration.
TiO 2 when used for blasting, caused significant enhancement of BIC in comparison to machined surfaces. 
Further enhancement in blasting was achieved through integration of bioceramic grit-blasting and acid etching (BGB/AE), to produce submicrometric topographies on implants. Evaluations showed significantly higher BIC and osteocyte density around modified implants as compared to simple dual-AE implants. Masaki  observed increased expression of type I collagen and alkaline phosphatase, key enzymes in biomineralization along bone-implant interface.
Different treatments are used to create hydrophilic implant surfaces (e.g., through chemical etching) to promote protein adhesion and cell attachment as implants with increased hydrophilicity exhibit faster integration with larger bone-to-implant contact.
The logical candidates for molecular grafting are proteins present in extracellular matrix, and implant surfaces that have been functionalized with fibronectin, vitronectin or laminin. 
Nanostructured metalloceramic coatings provide continuous variation from nanocrystalline metallic bond at interface to hard ceramic bond on surface. 
Nanostructured diamond causes good adhesion to Ti alloys. 
Nanostructured processing applied to HA coatings increases osteoblastic adhesion, proliferation and mineralization. 
| Interaction of Surface of Dental Implants with Blood|| |
During surgery, blood vessels are injured and implant surface interacts with blood components. Plasma proteins modified implant surface while activated platelets are responsible for thrombus formation and blood clotting. Migration of various cell types interacts with surface through membrane integrin receptors. These events occur before peri-implant tissue healing.
Blood interactions with implants lead to protein adsorption through complex series of adsorption and displacement steps known as Vroman effect. , After proteins absorption, osteointegration is characterized by platelet adhesion and fibrin clot formation at injured blood vessels site.
| Stem Cells and Bone Commitment|| |
Following blood clotting around dental implants, mesenchymal stem cells (MSCs) are attracted to injured site by chemotactic factors and have a determinant role in peri-implant tissue healing. MSCs are stem cells derived from somatic tissues which can be differentiated into mesenchymal lineages such as bone, cartilage, fat and skin.
Commitment and differentiation of MSCs towards osteogenic lineage is regulated by a certain group of factors [Figure 7]. Runx2, bone morphogenetic protein 2 (BMP 2), and distal-less homeobox 5 (Dlx 5) commit MSCs toward the osteogenic lineage. 
| Crosstalk Between Implant Surface and Stem Cells|| |
Migration, adhesion and proliferation
Integration of implant with neighboring bone and gingival tissues depend on successful crosstalk between old tissues and implant surface [Figure 8]. Cell migration, adhesion and proliferation on implant surface are prerequisite to initiate tissue regeneration. MSCs migration and proliferation were stimulated by growth factors including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), BMP2 and BMP4.  Plasma clot in contact with implant surface represents three-dimensional microporous structure that allows diffusion of regulatory factors  and is involved in migration, proliferation and differentiation of MSCs. After MSCs recruitment in injured site, cells adhere on local extracellular matrix and implant surface beginning extensive proliferation to build up new tissue.
|Figure 8: Intimate contact osteogenesis on the nanotextured implant surface|
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MSCs in contact with bone tissues switch to osteogenic cells while they differentiate into fibroblastic lineage in gingival tissue. These two pathways are in concurrence around dental implants. In some cases, implants are encapsulated by fibrous tissue due to proliferation and differentiation of MSCs into fibroblastic cells. In response to cytokines, fibroblasts migrate and generate collagen capsule, first step in generation of gingival tissue or rejection on contact to bone. This capsule prevents bonding between implant surface and bone and causes failure of the implant.  Both differentiation of MSCs into fibroblastic lineage and fibroblastic adhesion are desired in gingival upper part of dental implants[Figure 8]. Treatments as machining, grit blasting, Ti/HA plasma spray, chemical etching and anodization modify implant surface. Research demonstrate that nanorough Ti  and nanostructured Ti can enhance osteoblast adhesion and differentiation compared to nanosmooth control and enhance osseointegration [Figure 9]. 
|Figure 9: Difference in cellular surface interactions with and without nanofeatures|
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| Osseointegration of Dental Implants|| |
Cell-substratum interface serves not only as simple boundary of definition between host and implanted device, rather it presents primary cues for cellular adhesion and subsequent induction and tissue neogenesis.
Cells can use features as filopodia [Figure 10] to produce contact guidance with features as small as 10 nm high. Evidence that stem cells are exquisitely sensitive to their nanoenvironment adds further evidence that topographical environment is important for tissue-specific differentiation. 
Biomaterials that are biotolerable but never truly inert may be successfully employed for applications in which proteins absorbed on it and cellular interactions provide structural framework on which cellular adhesion may initiate. Modern implants make use of chemical and topographical modifications to regulate cellular adhesion, differentiation and de novo tissue deposition. 
|Figure 10: Filopodia of mesenchymal stem cells interacting with nanofeatures on the implant surface|
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| Conclusion|| |
Through this paper, importance of surface modifications on dental implant surfaces at nanometric level has been stressed upon. Nanotechnology has made numerous strides to improve bone-implant contact thus opening avenues of successful and durable implant therapy. However, the increasing interest in nanotechnology is undoubted and more researches are thus needed in this field.
Authors are greatful to Gaurav Khullar for his contribution in data collection.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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