Dental implants are poised to achieve significant growth as increasing populations become aware of the long term benefits associated with implant supported restorations and prostheses. Implant surface character is one implant design factor that affects the rate and extent of osseointegration. Nano-surface topography effectively enhances adherent osteoblasts differentiation and extracellular matrix formation / mineralization.
Dental implants are poised to achieve significant growth as increasing populations become aware of the long term benefits associated with implant supported restorations and prostheses. Implant surface character is one implant design factor that affects the rate and extent of osseointegration. Nano-surface topography effectively enhances adherent osteoblasts differentiation and extracellular matrix formation / mineralization.
Dental implants are poised to achieve significant growth as increasing populations become aware of the long term benefits associated with implant supported restorations and prostheses. Implant surface character is one implant design factor that affects the rate and extent of osseointegration. Nano-surface topography effectively enhances adherent osteoblasts differentiation and extracellular matrix formation / mineralization.
Dental implants are poised to achieve significant growth as increasing populations become aware of the long term benefits associated with implant supported restorations and prostheses. Implant surface character is one implant design factor that affects the rate and extent of osseointegration. Nano-surface topography effectively enhances adherent osteoblasts differentiation and extracellular matrix formation / mineralization.
Nanosurface The Future of Implants Keywords: Dental implants, Osteogenesis, Osseointegration, Topography, Surface treatment, Nanotechnology
GK THAKRAL 1 , RASHMI THAKRAL 2 , NEERAJ SHARMA 3 , JYOTSANA SETH 4 , PALLAVI VASHISHT 5 INTRODUCTION Dental implant is a prosthetic device made of alloplastic material (s) implanted into the oral tissues beneath the mucosal and/or periosteal layer, and on/or within the bone to provide retention and support for a xed or removable dental prosthesis. Dental implants are poised to achieve signicant growth as increasing populations become aware of the long term benets associated with implant supported restorations and prostheses. Economically viable and technologically advanced dental implants are fast shifting from an optional surgical procedure to a more acceptable and much sought- after treatment option for missing teeth. Majority of dental implants today are made of commercially pure (cp) titanium (1-4 grades) or titanium alloys like Ti-6Al-4V. Factors that contribute to the ultimate success of an implant include the physiological conditions of the recipient, implant placement procedure, implant material, implant design and implant surface. Implant surface character is one implant design factor that affects the rate and extent of osseointegration. Precisely how much of implant surface directly contacts bone, how rapidly this bone accrual occurs, and the mechanical nature of the bone/implant connection is inuenced by the nature of the implant surface itself [1,2]. There is a range of micron level surface topography that enhances the adherent osteoblasts differentiation and extracellular matrix formation/ mineralization. It has been shown that nano-surface topography effectively enhances extracellular matrix synthesis of adherent cells and provides a faster and more reliable osseointegration response as compared to conventional implant surface [3]. The impact of nanotechnology has begun to appear on the dental implant surface designs in a signicant manner. The technology involves increasing the complexity of the surface topography with the addition of nanoscale molecules [Table/Fig-1] [4]. It is now an established fact that surface topography plays a determinant role in the osseointegration procedure. Titanium oxide nano-tubes have shown an increased osseointegration compared to conventional titanium surfaces. The surface holds promise for improving the longevity of dental implants. Since osteoblasts readily adhere to this novel surface, dental implants coated with TiO 2 nanotubes could signicantly improve healing following dental implant surgery [Table/ Fig-2] [4]. Nanotechnology is bound to change the prospects and longevity of dental implants within the next decade. The article discusses distinct advantages of nanosurface modications over D e n t i s t r y
S e c t i o n conventional implant surface encompassing various aspects of dental implantology. Nano Technology Nanotechnology can be dened as the science and engineering involved in the design, synthesis, characterization and application of materials and devices whose smallest functional organization, in at least one dimension is on the nanometer scale or one billionth of a meter [5]. Nanotechnology therefore, involves materials that have a nano-sized topography or are composed of nano-sized materials ranging between 1 and 100 nm (109m) [6]. An evaluation of nano- mechanical properties of the surrounding bone by nano-indentation revealed that while both implants exhibited similar bone-to-implant contact, the nano-indentation demonstrated that the tissue quality ABSTRACT Nanotechnology is a relatively newer eld of science that is nding enormous scope in the dental & medical science. Use of endosseous dental implant surfaces having nano-scale topography is fast becoming part of modern implantology. The purpose of this review is to discuss and understand the role of nanoscale surface modication of titanium materials for the purpose of improving various phases of implantology including osseointegration. Nanotechnology equips bioengineers with newer ways of interacting with relevant biological processes. On the other hand, the eld of nanotechnology provides means of understanding and achieving cell specic functions. An understanding of the role of nano-topography leads to the signicant osseointegration modulations by nanoscale modication of the implants surface. Use of nanotechnology to modify the topography of titanium endosseous implant can drastically improve cellular and tissue responses that may benet osseointegration and dental implant procedures. [Table/Fig-1]: A cluster of titanium dioxide nanotubes [Table/Fig-2]: Bone cell anchoring to a surface of titanium dioxide nanotubes GK Thakral et al., Nanosurface The Future of Implants www.jcdr.net Journal of Clinical and Diagnostic Research. 2014 May, Vol-8(5): ZE07-ZE10 88 One of the main concerns related to coating the implant surface is the risk of coating detachment and toxicity of related debris. An evaluation of relationship of particle size and cell viability and proliferation compared to micron-particles revealed that nanoparticles of titanium and alumina had less negative impact in cell viability and proliferation as compared to conventional particles. There may be an advantage to nanoscale modication of surfaces using solgel coating methods. The quantum interaction of high electron density at the atomic level can enforce high bond strength between the substrate and nano-scale coating [3]. Studies reveal that the addition of a nanometer-scale calcium phosphate treatment to a dual acid-etched implant surface appeared to increase the extent of bone development after 4 and 8 weeks of healing. It was observed that this rapid accrual of bone at the implant surface expedites the implant healing period and supports early loading protocols [10]. Some of the commercial establishment manufacturing dental implants have already started using the technology to modify their products. Others are on a fast track to catch-up through the process of research and development. Nanotechnology and Cellular activity Studies have highlighted the signicance of micron-scale topography that compared various surface preparations of cp titanium to an electro-polished surface negative control-group and a hydroxyapatite coated positive control-group [11]. Their observation that a micron-scale rough surface prepared by grit blasting and subsequent acid etching was capable of rapid and increased bone accumulation further strengthened an earlier report that a TiO 2 grit blasted surface also supported more rapid and increased bone accrual at cp titanium implants [12]. The study also pointed to a signicant fact that the cp titanium surface could be modied to enhance bone accumulation and suggested that cp titanium was not only bioinert or biocompatible, but was also capable to inuence cellular activity or tissue responses leading to better and greater osteogenesis and thereby promoting better osseointegration. Nanotopography seems to inuence cell interactions at surface of the material being used. It also leads to changed cell behavior when compared to conventional sized topography. The cellular protein adsorption is altered by nanoscale modication of bulk material. Depending on the nano-architecture, cell spreading may be increased or decreased. The present undened mechanisms indicate that cell proliferation appears to be enhanced by nanoscale topography. Several investigators have shown that nanoscale topography enhances osteoblast differentiation [13-15] [Table/ Fig-4] [15]. Protein/surface interactions (surface wettability) in Nano-surface Alteration in initial protein surface interaction is believed to control osteoblast adhesion, a critical aspect of the osseointegration process was signicantly enhanced around the hydroxyapatite (HA)-coated implants [7]. Nanotechnology may involve one-dimensional concepts (nanodots and nanowires) or the self-assembly of more complex structures (nanotubes). Materials are also classied according to their form and structure as nanostructures, nanocrystals, nanocoatings, nanoparticles, and nanobers [6]. Nano-scale modication of the titanium endosseous implant surface may lead to alteration in the topography as well as chemistry of the surface. Therefore, the goal of nanoscale modication should be a specic chemical modication of cp titanium (grade 4 and 5). A distinct implication associated with nanoscale manipulation of any material is that it also leads to inherent chemical changes on the material surface. Albrektsson and Wennerberg [8] divided implant surface quality into three categories: i) mechanical properties, ii) topographic properties, and iii) physico- chemical properties. They pointed out that these characteristics are inter-related and a change in any of these groups affects the others as well. This signicant observation is quite relevant to the study of nano-surface modications of the endosseous cp titanium implant surface. METHODS OF IMPARTING NANO FEATURES There are various methods to create nanoscale features at the implant surface. These methods include: i) Physical methods, like self-assembly of mono-layers, compaction of nano particles and ion beam deposition; ii) Chemical methods, like acid etching, peroxidation, alkali treatment (NaOH) and anodization; iii) Nano particle deposition like sol-gel (colloidal particle deposition) and discrete crystalline deposition; and iv) Lithography and contact printing technique [Table/Fig-3] [9]. [Table/Fig-3]: Methods for creating nano-features on cp titanium implants Methods Characteristics Self-assembly of monolayers The exposed functional end group could be a molecule with different functions (an osteoinductive or cell adhesive molecule). Compaction of nanoparticles Conserves the chemistry of the surface among different topographies. Not readily applied over implant surfaces. Ion beam deposition Can impart nanofeatures to the surface based on the material used. Acid etching Combined with other methods (sandblasting and/or peroxidation) can impart nanofeatures to the surface and remove contaminants. Peroxidation Produces a titania gel layer. Both chemical and topography changes are imparted. Alkali treatment (NaOH) Produces a sodium titanate gel layer allowing hydroxyapatite deposition. Both chemical and topographic changes are imparted. Anodization Can impart nanofeatures to the surface creating a new oxide layer (based on the material used). Solgel (colloidal particle adsorption) Creates a thin-lm of controlled chemical characteristics. Atomic-scale interactions display strong physical interactions Discrete crystalline deposition Superimposes a nanoscale surface topographical complexity on the surface Lithography and contact printing technique Many different shapes and materials can be applied over the surface. Approaches are labor intensive and require considerable development prior to clinical translation and application on implant surface. [Table/Fig-4]: Depiction of broad range of nano-scale topography effects observed in cellular protein adsorption in bulk materials. Both cell specicity and extent of cell adhesion are altered. Depending on the nano-architecture cell spreading may be increased or decreased www.jcdr.net GK Thakral et al., Nanosurface The Future of Implants Journal of Clinical and Diagnostic Research. 2014 May, Vol-8(5): ZE07-ZE10 99 such as smooth muscle cells and chondrocytes have also reported similar results [25]. All these observations may lead to some major implications in specication of tissue response at bone and mucosal surface of the dental implant/abutment assembly. Differentiation A rapid differentiation of adherent mesenchymal cells along the osteoblast lineage is as signicant for the process of osseointegration as supporting osteoblast-specic adhesion and adherent cellular proliferation. Studies have revealed that alkaline phosphatase synthesis and calcium mineral content increased in cell layers formed on nanosized materials after 21 and 28 days [26, 27]. Nanosurface and bacterial proliferation Another signicant nding with nanosurfaces has been found to be a diminished bacterial adhesion and proliferation [28]. There was a marked decrease in bacterial colonization on nanostructured TiO 2 and ZnO irrespective of the fact that these surfaces promote osteoblast adhesion and differentiation. These initial observations may suggest the need for further exploration of the implant abutment surface with focus on biolm accumulation and peri-implantitis. Nanosurface and surface-reactivity Endosseous implant surface reactivity may get inuenced by nanosurface modications. Insignicant bone bonding occurs at endosseous titanium implants, especially during the initial phases of bone formation [29]. Nano-scale topographic modications tend to change the chemical reactivity of materials and presence of bone on implant surface during early stages [30]. Bone bonding seems to be an advantage associated with titanium implants with nano-scale surface modications. Nano-surface implants in dentistry Advantages of nanotopography on biomaterials have been demonstrated as early as 1999 by Webster et al., [25]. The nanotopography is linked to increased gene expression and is indicative of faster osteoblastic differentiation. Various options are available to impart nanoscale surface modications on implants [Table/Fig-3]. Some of these have already been commercially deployed and clinically used to enhance bone response. A positive bone response on nanosurface biomaterials is already an established fact. Up to what extent the nanotechnology and nanotopography can be used to improve tissue and abutment interface bonding remain to be seen. Commercially available current implants using nanotopography may not have acquired the level of microstructure desired for the ultimate goal of perfection in the area. Further research and study in the eld may open up new horizons of a more favorable use of titanium with nanosurface in implant dentistry. The development may well make dental implants last for life in the mouth with practically no failures. CONCLUSION Available research data may just be the tip of an iceberg on a very complex issue of nano-surface modications in implants and an improved bone response associated with it. Nanosurface modication changes the chemical / biological reaction of the implant in the mouth. This altered behavioral pattern has been linked to a changed implant surface interaction with ions, biomolecules and cells. This change in interactions, in turn favorably inuences molecular and cellular activities leading to altered osseointegration. It still needs to be explored whether this changed behavior can be attributed to the nanosurface modications alone. The inherent benets and limitations of nanostructure modications on implant surface will become evident on further evaluation and clinical trials after their long term use in human mouth. REFERENCES [1] Cooper LF. Biologic determinants of bone formation for osseointegration: clues for future clinical improvements. J Prosth Dent. 1998;80:43949. [16]. When implant comes in contact with a biological environment, the initiation of protein adsorption (e.g. plasma bronectin) promotes subsequent cell attachment and proliferation. Change in surface energy or wettability of a biomaterial corresponds to a typical way of altering cell interactions with the surface. Nano-scale topography is now an established way of altering protein interactions within a surface. Webster et al., demonstrated an increased vitronectin adsorption on nanostructured surfaces when compared to conventional surfaces [17,18]. Their study also suggested an increased osteoblast adhesion when compared to other cell types, such as broblasts, on the nanosurfaces [18]. Cell adhesion, spreading and motility in Nanosurface Irrespective of the surface-adsorbed proteins, cells are remarkable in their ability to sense nanostructure. Nano-features of a surface affect both cell adhesion and cell motility. Both of these cell traits are attributed in part, to the function of integrins [18,19]. Underlying substratum topography inuences cell behaviors by both direct and indirect interactions. In 2040 nm features produced by H 2 O 2 /H 2 SO 4
treatment there were denitive interactive points for lamellipodia of spreading cells [Table/Fig-5] [18]. Nano structure of alloplastic surfaces may have distinctive traits affecting cell interactions. Cell behavior is affected by both, the dimension and the density of the nano structures [20]. [Table/Fig-5]: Nanoscale topography-cell interactions on a nano-surface produced by H 2 O 2 /H 2 SO 4 treatment(A) 10,000_ image of adherent cell, (B) and (C) represent 100,000_images of the same adherent cell and (D) 200,000_ magnication of the cell with nano-features. (B) Higher magnication of the rectangle in (A). (D) Higher magnication of the rectangle in (B) Proliferation in Nano-surface Nanosurface modications promote adherent cell proliferation. Zhao et al., utilizing three distinct methods electrochemical machining, anodization and chemical etching to produce reproducible submicron-scale structures on titanium surfaces reported an opposing relationship between cell proliferation and cell differentiation with increase in micro scale of surface features [20]. It has further been supported by studies that observed an increase in the osteoblast proliferation on nano scale materials like alumina, titanium and hydroxyapatite [21,22]. However, the mechanism involved is still not clear as to how nanostructured surfaces modulate the adherent osteoblast response. Selectivity of adhesion in Nano-surface Selectivity of cell adhesion is an interesting feature attributed to nanoscale topographic surfaces. Several studies have revealed a relative lowering of broblast adhesion compared to osteoblast adhesion on evaluation of nano and micron-structured surfaces [23,24]. The afnity ratio between osteoblasts and broblasts was 3 to 1 on nanosized materials as compared to the conventional materials depicting a ratio of 1 to 1 [18]. Studies on other cell types GK Thakral et al., Nanosurface The Future of Implants www.jcdr.net Journal of Clinical and Diagnostic Research. 2014 May, Vol-8(5): ZE07-ZE10 10 10
PARTICULARS OF CONTRIBUTORS: 1. Professor, Department of Prosthodontics, SDCH, Rishikesh, India. 2. Professor, Department of Periodontology, SDCH, Rishikesh, India. 3. Senior Lecturer, Department of Prosthodontics, SDCH, Rishikesh, India. 4. Senior Lecturer, Department of Prosthodontics, SDCH, Rishikesh, India. 5. Senior Lecturer, Department of Prosthodontics, SDCH, Rishikesh, India. NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR: Dr. GK Thakral, Saket, Kinkraig Bridle Path, Kulri, Mussoorie-248179, India. Phone: +91-98-972-60666, E-mail: [email protected] FINANCIAL OR OTHER COMPETING INTERESTS: None. Date of Submission: Feb 03, 2014 Date of Peer Review: Apr 05, 2014 Date of Acceptance: Apr 07, 2014 Date of Publishing: May 15, 2014 [2] Nanci A, et al. Chemical modication of titanium surfaces for covalent attachment of biological molecules. J Biomed Mater Res. 1998;40:32435. [3] Gutwein LG, Webster TJ. Increased viable osteoblast density in the presence of nanophase compared to conventional alumina and titania particles. IJ Biomaterials. 2004;25:417583. [4] Tolou Shokuhfar, et al. Intercalation of anti-inammatory drug molecules within TiO2 nanotubes. JRSC Adv. 2013;3(38):17380-6. [5] Silva GA. Introduction to nanotechnology and its application to medicine. J SurgNeurol. 2004;61:216-20. [6] Christenson EM, et al. Nanobiomaterial applications in orthopedics. J Orthop Res. 2007;25:1122. [7] R Jimbo, et al. Nano Hydroxyapatite-coated Implants Improve Bone Nanomechanical Properties. JDR. 2012:91:121172-7. [8] Albrektsson T, Wennerberg A. Oral implant surfaces: part 1, Focusing on topographic and chemical properties of different surfaces and in vivo responses to them. Int J Prosth. 2004;17:53643. [9] Webster TJ, Ejiofor JU. Increased osteoblast adhesion on nanophasemetals:Ti, Ti6Al4V, and CoCrMo. IJ Biomaterials. 2004;25:47319. [10] Goene RJ, et al. Inuence of a nanometer-scale surface enhancement on de novo bone formation on titanium implants: a histomorphometric study in human maxillae. Int J Perio Restorative Dent. 2007;27:2119. [11] Gotfredsen K, et al. Clinical and radiographic evaluation of submerged and nonsubmerged implants in monkeys. Int J Prosth. 1990;3:4639. [12] Klabunde KJ, et al. Nanocrystals as stoichiometric reagents with unique surface chemistry. J Phys Chem. 1996; 100:121. [13] Wu SJ, et al. Sintering of nanophase g-Al2O3 powder. J Am Ceram Soc. 1996; 79: 2207. [14] Baraton MI, et al. FTIR study of nanostructured alumina nitride powder surface: determination of the acidic/basic sites by CO, CO 2 , and acetic acid adsorptions. J Nano Mater. 1997;8:435. [15] Balasundaram G, et al. Using hydroxyapatite nanoparticles and decreased crystallinity to promote osteoblast adhesion similar to functionalizing with RGD. IJ Biomaterials. 2006;27:2798805. [16] Webster TJ, et al. Mechanisms of enhanced osteoblast adhesion on nanophase alumina involve vitronectin. J Tissue Eng. 2001;7:291301. [17] Webster TJ, et al. Specic proteins mediate enhanced osteoblast adhesion on nanophase ceramics. J Biomed Mater Res. 2000;51:47583. [18] Brunette DM. The effects of implant surface topography on the behavior of cells. Int J Oral Maxillofac Implants. 1988;3:2314. [19] Cavalcanti Adam EA, et al. Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. Biophys J. 2007;92:296474. [20] Zhao G, et al. Osteoblastlike cells are sensitive to submicron-scale surface structure. Clin Oral Implants Res. 2006;17:25864. [21] Webster TJ, et al. Enhanced functions of osteoblasts on nanophase ceramics. IJ Biomaterials. 2000;21:180310. [22] Price RL, et al. Osteoblast function on nanophase alumina materials: inuence of chemistry, phase, and topography. J Biomed Mater Res A. 2003;67:128493. [23] McManus AJ, et al. Evaluation of cytocompatibility and bending modulus of nanoceramic/polymer composites. J Biomed Mater Res. A 2005;72:98106. [24] Price RL, et al. Nanometer surface roughness increases select osteoblast adhesion on carbon nanober compacts. J Biomed Mater Res A. 2004;70:129 38. [25] Webster TJ, et al. Osteoblast adhesion on nanophase ceramics. IJ Biomaterials. 1999;20:12217. [26] Meirelles L. On nano size structures for enhanced early bone formation [Ph.D.]. Gothenburg: J Gothenburg University; 2007. [27] Colon G, et al. Increased osteoblast and decreased Staphylococcus epidermidis functions on nanophase ZnO and TiO2. J Biomed Mater Res A. 2006;78:595 604. [28] Davies JE. Bone bonding at natural and biomaterial surfaces. IJ Biomaterials. 2007;28:505867. [29] Tasker LH, et al. Applications of nanotechnology in orthopaedics. Clin Orthop Relat Res. 2007;456:2439. [30] Ellingsen JE, et al. Improved retention and bone-to-implant contact with uoride- modied titanium implants. IJ Oral Maxillofac Implants. 2004;19:65966.