INTRODUCTION
Osseointegration is widely accepted as a vital factor for dental implant success.[1] The quality and rate of osseointegration are majorly affected by surface morphology, its composition, chemical, physical, and biomechanical properties.[2] Various techniques have been introduced over time to enhance the bioactivity of osteogenic cells in peri-implant area and ensure the success of bone-implant interface.[3] Different surface properties will induce completely different sequence and supermolecule expression within the osteogenic cells and conjointly different structural and biomechanical properties to the encompassing mineralized tissue[4,5] resulting in enhanced rate, amount, and quality of peri-implant bone formation.[6]
REVIEW
Biocompatibility of material
The biocompatibility profiles of bulk materials are undoubtedly an important concern in osseointegration. Their physical, mechanical, chemical, and electrical properties offer key inputs into the reticulate biomechanical and biological functions. In general, ceramic and titanium are used. The distinctive properties of ceramic materials, together with their corrosion resistance and glorious aesthetics, make them appealing candidates for several dental applications. However, their inferior mechanical properties, lower fracture resistance, hamper their load-bearing capacity.[7]
Titanium, over a decade, has evolved as a commonly used material due to its biocompatibility, high corrosion resistance, low weight, high strength/weight magnitude relation, and chemical stability (Commercially pure Titanium [CpTi]) and its alloys are commonly used in manufacturing dental implants. Although CpTi has higher corrosion resistance low mechanical strength compared to Ti–6Al–4V which has higher mechanical strength and fatigue resistance.[8] A crucial property of titanium is that the passive compound layer formed on surface which plays a crucial role in corrosion resistance, biocompatibility, and osteointegration.[9]
Polymeric implants made of polymethylmethacrylate and polytetraflouroethylene came into existence in 1930, however, their use is currently limited.[10]
Polyetheretherketone has been more and more used as a biomaterial for orthopedic and spinal implants because of their osseointegration capacity.[11] However, whether or not these implants can be used as viable alternative to titanium, is still under research. They have ketone and ether functional groups attached to the aromatic backbone[12] which provide stability at higher temperatures, resistance to chemical and radiation injury, bioinertness, compatibility with several reinforcing agents as glass and carbon fibers, and a larger strength on a per mass basis than several metals. Studies show that they are osteoconductive and promote proliferation and growth of osteoblastic cells in human.[13]
Importance of implant surface in osseointegration
Immediately after implant placement, a complex series of events occurs between the host bone and implant surface. This includes the initial interaction between blood and the implant surface, where proteins and ligands are dynamically adsorbed onto and released from the implant surface, through an inflammatory process, which is followed by initial bone formation around the implant (modeling), and through several remodeling cycles, where the bone surrounding the implant achieves its highest degree of organization and mechanical properties.[14] Precisely how much of the implant surface directly contacts bone, how rapidly this bone accrual occurs, and the mechanical nature of the bone/implant connection is influenced by the nature of the implant surface itself.[15,16] Molecular investigations have contributed to defining cellular responses to titanium as “compatible” and advantageous. For example, Amengual et al. showed relatively low inflammatory signaling within cells in tissues adjacent to titanium implants and suggested that this is a part of the osseointegration process.[17]
During the first 10–20 years of applied end osseous implant experience, the concept that titanium implant biocompatibility supported clinical osseointegration success dominated clinical thinking. The different physic/chemical properties can potentially lead to changes in the host-to-implant response.[18] In addition, specific surface effects on initial bone healing kinetics and mechanical properties evolution as implantation time elapse in vivo, as well as the in vivo stability of the surface (often regarded as one of the leading factors of long-term osseointegration) should be hierarchically investigated to more fully evaluate implant therapy surgical and or prosthetic protocol modifications.[9]
SURFACE ROUGHNESS OF IMPLANT ON THE BASIS OF IRREGULARITY SIZE
Micro scale surface irregularities
The significance of micron-scale topography was highlighted in an important report by Busser et al. that compared various surface preparations of titanium to an electro polished surface negative control and a hydroxyapatite-coated positive control group. These surfaces were capable of rapid and increased bone formation and osseointegration. At least, three different lines of thinking have evolved to better interpret or explain how surface topography at the micron-scale can increase bone-to-implant contact. One is the biomechanical theory of Hansson and Norton, the second is the concept of contact osteogenesis, and the third is a surface signaling hypothesis supported by many cell culture investigations.
Hansson has elegantly described the theoretical interaction of bone with the implant surface and mathematically defined the role of surface roughness at the micron-scale within this hypothetical construct. The result of the theoretical calculations – that an implant surface should be densely covered with pits of approximately 1.5 mm depth and 3–5 mm diameter – is supported by data collected in a series of studies on implant topography effects on bone-to-implant contact. There is an appreciation that the mechanical interlocking of bone is essential to the improved performance of endosseous implants.[19,20,21,22]
A principal role for fibrin clot stabilization by the interlocking of fibrin fibers with the surface features which promotes the directed on the growth of bone-forming cells directly at the implant/bone interface.[23] Topographic enhancement may aid in the stabilization of fragile extracellular matrix scaffolds for conduction of cells toward and onto the implant surface (contact guidance). A clearly defined role for extracellular matrix proteins-receptors (integrin) has been proposed to transduce topography-specific signals to the adherent cells. One possible way that topography may alter cellular differentiation is through imposed changes in cell shape.[24] Micron-level topography effects on increased bone-to-implant contact are observed in vivo, and in human clinical histology. Limited evidence that integrins are involved in cellular responses to implant surfaces has been obtained using MG63 cell culture studies.[24,25]
Nanoscale surface irregularities
These irregularities are of size range between 1 and 100 nm. The application of nanotechnology to the dental implant surface involves a two-dimensional association of surface features (across and away from the mean surface plane). These nanofeatures can be arranged in an organized manner (isotropic) or unorganized manner (anisotropic), often depending on the method of manufacture.[26] Isotropic features such as nanogrooves or nano pits that are created largely by optical methods are not readily applied to complex screw-shaped objects.[27,28] When these concepts are applied to the endosseous implant surface, it led to novel physicochemical behavior (e.g., bone-bonding) or biochemical events (e.g., altered protein adsorption, cell adhesion with changes in cell behavior).
The nanoscale modification affects both the morphology and the chemistry of the implant surface. A complicating feature of nanoscale manipulation of any material is that there are inherent chemical changes in the bulk material surface.
Nanotechnology requires newer methods of manipulating matter on the atomic scale. Several techniques are currently prevalent in the experimental application to endosseous implants.[29,30,31]
- The physical method of compaction of nanoparticles forming surfaces with nanoscale grain boundaries. An advantage of this method is that it conserves the chemistry of the surface among different topographies
- The process of molecular self-assembly. An example of this is the use of cell adhesive peptide domains (RGD domains) appended to self-assembly monolayer composed of polyethylene glycol and applied to the titanium implant surfaces[32]
- The chemical treatment of different surfaces to expose reactive groups on the material surface and create nanoscale topography. The NaOH treatment, H2O2 with acid etching, and treatment with hydrofluoric acid have been shown to create novel nanostructures of amorphous titanium oxide on the implant surface[33]
- Sol–gel transformation techniques achieve deposition of nanometer-scale calcium phosphate (CaP) accretions to the implant surface. The quantum interaction of high electron density at the atomic level can enforce high bond strength between the substrate and nanoscale coating. Examples of this have been reported for the CaP/discrete crystalline deposition (DCD) sol–gel coating of Ti alloy implant surfaces[34]
- The use of optical methods (typically lithography) reliant on wavelength-specific dimensions to achieve the appropriate methods for creating nanofeatures on cp-Ti implants.
Nanotopography results in enhanced cell adhesion, proliferation, differentiation, and cell-specific adhesion. Nanostructure imparts important chemical changes and permits biomimetic relationships between alloplastic surfaces and tissues. It is speculated that alloplastic nanosurfaces possess topographic elements scaled to naturally occurring substrates.[35,36,37,38]
METHODS OF SURFACE MODIFICATION
The various techniques used for surface modification aim at creating irregularities on the implant surface. Some techniques add material to give positive irregularities in contrast to others where particles will be removed from the surface, creating negative pits on the surface.
These are as follows:
SUBSTRACTIVE METHODS
Turned or machined dental implant surface
These are first generation of dental implants, which after being manufactured, are submitted to cleaning, decontamination, and sterilization procedures. The main disadvantage regarding the morphology of non-treated implants is the fact that osteoblastic cells are prone to grow along the grooves existing on the surface, which in terms of clinical implications means a longer healing time required. Studies have shown lower primary stability for the turned implants, while the secondary stability values and clinical success rates similar to other modified implants.[39] Due to lower resistance to removal torque, turned dental implants are becoming now mostly commercially unavailable.
Grit-blasting or sand blasting of implant surface
In this hard ceramic particles that are projected through a nozzle at high velocity toward the metallic substrate by means of compressed air and leading to different surface roughness, depending on the size of the ceramic particles.[40] This is usually performed with particles of silica (sand), alumina, titanium dioxide, or resorbable bioceramics such as calcium phosphate (CaP) producing surface irregularity of 1–2 μm. However, it is often embedded into the implant surface and residue remains even after ultrasonic cleaning, acid passivation and sterilization, and released later into the surrounding tissues interfering with the osteointegration.
Acid – Ethching implant surface
The immersion of a titanium dental implant in strong acids such as HCl, H2SO4, HNO3, and HF produces micro pits on titanium surfaces with sizes ranging from 0.5 to 2 μm in diameter. The resulting surface shows homogenous roughness, increased active surface area and improved adhesion of osteoblastic lineage cells. Dual acid-etching with a mixture of concentrated HCl and H2SO4 heated above 100°C to produce a micro-rough surface that may enhance the osteoconductive process through the attachment of fibrin and osteogenic cells, resulting in bone formation directly on the surface of the implant. Various studies hypothesized that implants treated by dual acid-etching have a specific topography able to attach to fibrin, improving the adhesion of osteogenic cells, and thus, promoting bone apposition. However, acid-etching can lead to hydrogen embrittlement of the titanium, creating micro cracks on its surface that could reduce the fatigue resistance of the implants which is related to the occurrence of fracture in dental implants.[41]
Grit-blasting and acid etching
In this following grit-blasting, the surface is submitted to acid-etching to further enhance the topographic profile of the surface and remove processing by products. The advantages of this method include an increase in the total surface area of the implant, achieved due to the selective removal resulting from electrochemical differences in the surface topography.[42,43] Nevertheless, this process should be carried out under controlled conditions, as over-etching the surface decreases surface topography and mechanical properties and may be detrimental to osteointegration. In addition, it is important that the etching procedures following grit-blasting removes any particle remaining, because chemical analyses of failed implants have shown evidence that the presence of such particles interferes with titanium osteoconductivity regardless of the established biocompatibility profiles of the biomaterial.
Anodisation of implant surface
In order to alter the topography and composition of the surface oxide layer of the implants, micro- or nano-porous surfaces may also be produced by potentiostatic or galvanostatic anodization of titanium in strong acids, such as sulfuric acid, phosphoric acid, nitric acid and hydrogen fluoride at high current density or potential. When strong acids are used in an electrolyte solution, the oxide layer will be dissolved along current convection lines and thickened in other regions which creates micro- or nano-pores on the titanium surface. This electrochemical process results in an increased thickness and modified crystalline structure of the titanium oxide layer. However, it is a complex procedure and depends on various parameters such as current density, concentration of acids, composition, and electrolyte temperature.[44]
ADDITIVE METHODS
Titanium plasma spraying hydrdoxyapettite surface coating method
Titanium plasma spraying (TPS) consists of injecting titanium particles into a plasma torch at high temperature, these particles are projected on to the surface of the implants where they condense and fuse together, forming a film about 30 μm thick resulting in an average roughness of around 7 μm. This increases the surface area of dental implants up to approximately six times and is dependent on implant geometry and processing variables, such as initial powder size, plasma temperature, and distance between the nozzle output and target. Plasma sprayed hydroxyapatite (PSHA) coatings are the most commonly found among the commercially available CaP coatings. The HA ceramic particles are heated to extremely high temperatures and deposited at a high velocity onto the metal surface where they condense and fuse together forming a 20–50 μm thick film. This resulting surface shows enhanced bioactivity, but, the mechanical resistance of the interface between the coating and titanium is considered to be a weak point, which has been further reports as cause of failure.[45]
Despite the substantiality for PSHA-coated implants, uniform coating composition and crystallinity have not always been achieved through the plasma spray process, and the overall literature database is controversial with respect to coating composition and crystalline content in relation to the in vivo performance.[44,45,46]
In order to improve PSHA coatings, a number of techniques have been developed with the aim of producing a thin-film nanostructured bioceramic coatings, such as sol–gel deposition, pulsed laser deposition, sputtering coating techniques, electrophoretic deposition, and ion-beam-assisted deposition. These techniques may offer a more accurate compositional control and the possibility of fabricating much thinner layers of the order of 1 μm or less which is advantageous for coating stability.
Calcium phosphate surface coating
CaP coatings, mainly composed of hydroxyapatite, have been used as a biocompatible, osteoconductive and resorbable blasting materials. In the resorbable ones, following implantation, the release of CaP into the peri-implant region increases the saturation of body fluids and precipitates a biological apatite onto the surface of the implant serving as a matrix for osteogenic cell attachment.[47]
However, recurrent drawbacks include controlling the calcium-phosphate layer composition, resorb ability, weak adhesion to the substrates, the use of high temperatures or the costs involved in the process. In fact, there are several reports of cracking and/or delamination of the coating due the generation of large thermal stresses during processing, which may affect the quality and rate of peri-implant bone formation.
Biomimetic calcium phosphate coatings
These involves the use of microstructures and functional domains of organismal tissue function to deposit CaP upon medical devices to improve their biocompatibility. This bioinspired method consist in the precipitation of CaP apatite crystals onto the dental implant surface through simulated body fluids under near-physiological or “biomimetic” conditions of temperature and pH.[48]
Ion beam-assisted deposition of nanothickness bioceramic coatings
It is an attempt to increase surface osteoconductivity while avoiding the limitations presented by the standard PSHA coating process, substantially thinner coatings (ranging in the nanometer to the micrometer thickness) have been applied on implant surfaces. Desirable features of thin-film coatings include coating controlled composition and thickness plus enhanced adhesion to the metallic substrate (40 MPa vs. \20 MPa for PSHA-coated implants) thereby potentially increasing osteoconductivity at early implantation times. However, rapid dissolution of thin films may result in the exposure of the metallic substructure.[49] Animal studies at early implantation times including sputtering-coated and ion beam-assisted deposition (IBAD)-coated Ca-and P-based thin-films on titanium implants have demonstrated higher biomechanical fixation bioactivity and BIC with 300–500 nm coating when compared with 20–50 nm coating thickness at early implantation times. A potential drawback of the novel processing techniques for thin-film deposition is its relatively high cost for large-scale production.[50]
Calcium phosphate discrete crystalline deposition method
Another engineering-based approach to incorporate Ca-and P-based components onto implant surfaces is the DCD method. This process incorporates nanometer-size crystals of CaP onto a previously treated surface (dual acid-etch). The DCD method yields a surface which is different in morphology and microstructure than IBAD and other thin coating deposition methods. This provides an increased osseoconductive component to the implant surface. Limitation of the studies on the DCD surface includes the measurement of bone-bonding by pullout force assessment in specimens of irregular shape and the utilization of implant shapes that are not representative of the endosseous implant in which the DCD surface is commercially available. Nonetheless, the DCD surface has shown promising results in a study in humans, where higher BIC was found after 2 months in vivo.[51]
Other techniques for incorporation of calcium and phosphorous at the nanometer scale
Other alternatives to commercially to IBAD and DCD have been explored to chemically modify implant surfaces to provide elemental Ca and P on rough implant surfaces. The technique comprises a combination of surface treatments used to increase implant surface roughness.[52] This modification of grit-blasting the surface with biocompatible bio ceramics (RBM) added to a selective cleaning procedure (modified acid-etching procedures) leading to a moderately rough surface with Ca and P remnants in the surface. From a theoretical standpoint, all “nano” surfaces presented may be a benefit from both surface roughness and chemistry viewpoints.[53] They have shown enhancement of the host response to implants. Although promising results have been obtained in preliminary studies and short-term clinical trials, more laboratory in vivo and controlled clinical trials should be performed to better characterize the performance of these surfaces at short- and long-term implantation times.
Biochemical methods of the surface modifications
The biochemical methods of the surface modifications offer an adjunct to the physiochemical and the morphological methods. Their goal is to immobilize proteins, enzymes, or peptides on biomaterials to induce specific cell and tissue responses. One approach uses cell-adhesion molecules such as fibronectin, vitronectin, Type I collagen, osteogenin, and bone sialoprotein.[54] While the second approach uses biomolecules with osteotropic effects which range from mitogenicity (interleukin growth factor-I, fibroblast growth factor-2, platelet-derived growth factor-BB) to the increasing activity of the bone cells, thereby enhancing the collagen synthesis for osteoinduction. The application of various biotolerant agents, for example, rhBMP-2, within the confined boundaries of the hollow chambered implant, has been tried to modify the surface topography or the chemistry of the implants.[55]
Photofunctionalization
Ultraviolet (UV) treatment of dental implant promotes interaction of cells and proteins to the implant on a molecular level, UV light is believed to enhance the osteoconductivity. It has been suggested to raise the level of protein absorption and cellular attachment to titanium surfaces and has been shown to restore bioactivity caused by age-related degradations.[56]
Nanotitania coatings
Nanotitania coatings were prepared using the sol-gel technique. Commercially available tetra isopropyl orthotitanate was dissolved in absolute ethanol. Ethyleneglycol monoethylether, deionized water, and fuming HCl 37% were dissolved in ethanol. The two solutions were mixed rapidly and stirred effectively for 3 min. The coating sol was aged at 0°C for 24 h before the Ti substrates were dip coated and the substrate was withdrawn at 0.30mm/s. The coated substrates were heat treated at 500°C for 10 min, cleaned ultrasonically in acetone for 5 min and dried at ambient temperature. The Nanotitania implants had an increased feature density and a large feature coverage area as compared to the nano-HA implants. This could present more binding sites for the protein cell attachment and for increased bone contact. The Nanotitania implants exhibited an ordered arrangement, forming a homogeneous layer on underlying topography.[57]
CONCLUSION
One of the main purposes for modifying dental implant surface is to decrease the healing period time for osseointegration. Along with implant macrodesign evolution, surface treatment appears to be another step toward minimizing healing period times before implant restoration[38,58] The available literature so far suggests that increases in surface texture through a variety of techniques favors wound healing and appear to be potentially advantageous at early implantation times despite little evidence of its long-term beneficial effect.
The emerging technology comprising bioceramic coatings at nanoscale dimensions appears to benefit from surface topographies and chemistries to increase surface osteoconductivity. This technology is under active basic and clinical investigation to determine what the prevailing properties (surface chemistry or subnanometer level texturing) may lead to the most favorable results.
The clinician is faced with a wide range of competing products with many different surface treatments. The actual nature of the surfaces on these implants and their manufacturing control is of concern.[53]
Given the number of products and surface treatments under study, the clinician should ask, based on the in vitro, in vivo data as well as the results of clinical studies as to effectiveness before use of any dental implant.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Bornstein MM, Cionca N, Mombelli A. Systemic conditions and treatments as risks for implant therapy Int J Oral Maxillofac
Implants. 2009;24(Suppl):12–27
2. Javed F, Ahmed HB, Crespi R, Romanos GE. Role of primary stability for successful osseointegration of dental
implants: Factors of influence and evaluation Interv Med Appl Sci. 2013;5:162–7
3. Santos Maria Cristina Leme Godoy Dos, et al Early dental implant failure: A review of the literature Brazilian Journal of Oral Sciences. 2002;1:103–11
4. Dierens M, Vandeweghe S, Kisch J, Nilner K, De Bruyn H. Long-term follow-up of turned single
implants placed in periodontally healthy patients after 16-22 years: Radiographic and peri-implant outcome Clin Oral
Implants Res. 2012;23:197–204
5. Ravald N, Dahlgren S, Teiwik A, Gröndahl K. Long-term evaluation of Astra Tech and brånemark
implants in patients treated with full-arch bridges. Results after 12-15 years Clin Oral
Implants Res. 2013;24:1144–51
6. Zarb GA, Schmitt A. Osseointegration and the edentulous predicament. The 10-year-old toronto study Br Dent J. 1991;170:439–44
7. Abraham CM. A brief historical perspective on dental
implants, their surface coatings and treatments Open Dent J. 2014;8:50–5
8. Cooper LF. A role for surface
topography in creating and maintaining bone at titanium endosseous
implants J Prosthet Dent. 2000;84:522–34
9. Bhasin SS, Perwez E, Sachdeva S, Mallick R. Trends in prosthetic biomaterials in implant dentistry J ICDRO. 2015;7:148–59
10. Saini M, Singh Y, Arora P, Arora V, Jain K. Implant biomaterials: A comprehensive review World J Clin Cases. 2015;3:52–7
11. Fujihara K, Huang ZM, Ramakrishna S, Satknanantham K, Hamada H. Performance study of braided carbon/PEEK composite compression bone plates Biomaterials. 2003;24:2661–7
12. Fujihara K, Huang ZM, Ramakrishna S, Satknanantham K, Hamada H. Feasibility of knitted carbon/PEEK composites for orthopedic bone plates Biomaterials. 2004;25:3877–85
13. Kurtz SM, Devine JN. PEEK biomaterials in trauma, orthopedic, and spinal
implants Biomaterials. 2007;28:4845–69
14. Junker R, Dimakis A, Thoneick M, Jansen JA. Effects of implant surface coatings and composition on bone integration: A systematic review Clin Oral
Implants Res. 2009;20(Suppl 4):185–206
15. Thakral G, Thakral R, Sharma N, Seth J, Vashisht P. Nanosurface – The future of
implants J Clin Diagn Res. 2014;8:E07–10
16. Wennerberg A, Albrektsson T. On implant surfaces: A review of current knowledge and opinions Int J Oral Maxillofac
Implants. 2010;25:63–74
17. Amengual-Peñafiel L, Córdova LA, Constanza Jara-Sepúlveda M, Brañes-Aroca M, Marchesani-Carrasco F, Cartes-Velásquez R. Osteoimmunology drives dental implant osseointegration: A new paradigm for implant dentistry Jpn Dent Sci Rev.. 2021;57:12–19 Epub 2021 Feb 16. PMID: 33737990; PMCID: PMC7946347.
18. Bowers KT, Keller JC, Randolph BA, Wick DG, Michaels CM. Optimization of surface micromorphology for enhanced osteoblast responses
in vitro Int J Oral Maxillofac
Implants. 1992;7:302–10
19. Mustafa K, Wroblewski J, Hultenby K, Lopez BS, Arvidson K. Effects of titanium surfaces blasted with TiO2 particles on the initial attachment of cells derived from human mandibular bone. A scanning electron microscopic and histomorphometric analysis Clin Oral
Implants Res. 2000;11:116–28
20. Buser D., Schenk R. K., Steinemann S., Fiorellini J. P., Fox C. H., Stich H.. “Influence of surface characteristics on bone integration of titanium
implants. A histomorphometric study in miniature pigs,” Journal of Biomedical Materials Research. 1991;Vol. 25(7):889–902
21. Chang PC, Lang NP, Giannobile WV. Evaluation of functional dynamics during osseointegration and regeneration associated with oral
implants Clin Oral
Implants Res. 2010;21:1–12
22. . Stig Hansson, Michael Norton, The relation between surface roughness and interfacial shear strength for bone-anchored
implants. A mathematical model Journal of Biomechanics. 1999;32(8):829–836
23. Smeets R, Stadlinger B, Schwarz F, Beck-Broichsitter B, Jung O, Precht C, et al Impact of Dental Implant Surface Modifications on Osseointegration Biomed Res Int.. 2016;2016:6285620 Epub 2016 Jul 11. PMID: 27478833; PMCID: PMC4958483.
24. Kroening S, Goppelt-Struebe M. Analysis of matrix-dependent cell migration with a barrier migration assay Sci Signal. 2010;3:pl1
25. Piattelli A, Manzon L, Scarano A, Paolantonio M, Piattelli M. Histologic and histomorphometric analysis of the bone response to machined and sandblasted titanium
implants: An experimental study in rabbits Int J Oral Maxillofac
Implants. 1998;13:805–10
26. Roccuzzo M, Aglietta M, Bunino M, Bonino L. Early loading of sandblasted and acid-etched
implants: A randomized-controlled double-blind split-mouth study. Five-year results Clin Oral
Implants Res. 2008;19:148–52
27. Sezin M, Croharé L, Ibañez JC. Microscopic study of surface microtopographic characteristics of dental
implants Open Dent J. 2016;10:139–47
28. Mendonça G, Mendonça DB, Aragão FJ, Cooper LF. Advancing dental implant surface technology--from micron- to nanotopography Biomaterials. 2008;29:3822–35
29. Wennerberg A, Albrektsson T, Andersson B, Krol JJ. A histomorphometric and removal torque study of screw-shaped titanium
implants with three different surface topographies Clin Oral
Implants Res. 1995;6:24–30
30. Gittens RA, Olivares-Navarrete R, Schwartz Z, Boyan BD. Implant osseointegration and the role of microroughness and nanostructures: Lessons for spine
implants Acta Biomater. 2014;10:3363–71
31. Gaviria L, Salcido JP, Guda T, Ong JL. Current trends in dental
implants J Korean Assoc Oral Maxillofac Surg. 2014;40:50–60
32. Whitesides GM, Kriebel JK, Love JC. Molecular engineering of surfaces using self-assembled monolayers Sci Prog. 2005;88:17–48
33. Sharma A, Rahul GR, Poduval S, Sharma R. Implant surface micro-design Glob J Med Res J Dent Otolaryngol. 2014;14(4)
34. Wennerberg A, Hallgren C, Johansson C, Danelli S. A histomorphometric evaluation of screw-shaped
implants each prepared with two surface roughnesses Clin Oral
Implants Res. 1998;9:11–9
35. Deogade S. Current Status of Nanotechnology Methods Applied For Dental
Implants International Journal of Pharmaceutical Science Invention. 2015;4:32–43
36. Larsson C, Thomsen P, Aronsson BO, Rodahl M, Lausmaa J, Kasemo B, et al Bone response to surface-modified titanium
implants: Studies on the early tissue response to machined and electropolished
implants with different oxide thicknesses Biomaterials. 1996;17:605–16
37. Ivanoff CJ, Widmark G, Johansson C, Wennerberg A. Histologic evaluation of bone response to oxidized and turned titanium micro-
implants in human jawbone Int J Oral Maxillofac
Implants. 2003;18:341–8
38. Zechner W, Tangl S, Fürst G, Tepper G, Thams U, Mailath G, et al Osseous healing characteristics of three different implant types Clin Oral
Implants Res. 2003;14:150–7
39. Chehroudi B, Gould TR, Brunette DM. Titanium-coated micromachined grooves of different dimensions affect epithelial and connective-tissue cells differently
in vivo J Biomed Mater Res. 1990;24:1203–19
40. Orsini G, Assenza B, Scarano A, Piattelli M, Piattelli A. Surface analysis of machined versus sandblasted and acid-etched titanium
implants Int J Oral Maxillofac
Implants. 2000;15:779–84
41. Memoli VA, Woodman JL, Urban RM, Galante JO. Long term biocompatibility of the porous titanium fibre metal composites [Abstract] Presented at the 29th Annual Orthopaedic Research Society, Anaheim, California; 8-10 March,. 1983
42. Blumenthal NC, Cosma V. Inhibition of apatite formation by titanium and vanadium ions J Biomed Mater Res. 1989;23:13–22
43. Lugowski SJ, Smith DC, McHugh AD, Van Loon JC. Release of metal ions from dental implant materials
in vivo: Determination of Al, Co, Cr, Mo, Ni, V, and Ti in organ tissue J Biomed Mater Res. 1991;25:1443–58
44. Jimbo R, Sawase T, Baba K, Kurogi T, Shibata Y, Atsuta M. Enhanced initial cell responses to chemically modified anodized titanium Clin Implant Dent Relat Res. 2008;10:55–61
45. Özcan M, Hämmerle C. Titanium as a Reconstruction and Implant Material in Dentistry: Advantages and Pitfalls Materials (Basel).. 2012;5(9):1528–45 PMCID: PMC5449026.
46. Hägi TT, Enggist L, Michel D, Ferguson SJ, Liu Y, Hunziker EB. Mechanical insertion properties of calcium-phosphate implant coatings Clin Oral
Implants Res. 2010;21:1214–22
47. Carreira AC, Lojudice FH, Halcsik E, Navarro RD, Sogayar MC, Granjeiro JM. Bone morphogenetic proteins: facts, challenges, and future perspectives J Dent Res. 2014;93:335–45
48. Schliephake H, Scharnweber D, Roesseler S, Dard M, Sewing A, Aref A. Biomimetic calcium phosphate composite coating of dental
implants Int J Oral Maxillofac
Implants. 2006;21:738–46
49. Coelho PG, Cardaropoli G, Suzuki M, Lemons JE. Histomorphometric evaluation of a nanothickness bioceramic deposition on endosseous
implants: A study in dogs Clin Implant Dent Relat Res. 2009;11:292–302
50. Coelho PG, Lemons JE. Physico/chemical characterization and
in vivo evaluation of nanothickness bioceramic depositions on alumina-blasted/acid-etched Ti-6Al-4V implant surfaces J Biomed Mater Res A. 2009;90:351–61
51. Mendes VC, Moineddin R, Davies JE. The effect of discrete calcium phosphate nanocrystals on bone-bonding to titanium surfaces Biomaterials. 2007;28:4748–55
52. Browne M, Gregson PJ. Effect of mechanical surface pretreatment on metal ion release Biomaterials. 2000;21:385–92
53. Taba Júnior M, Novaes AB Jr, Souza SL, Grisi MF, Palioto DB, Pardini LC. Radiographic evaluation of dental
implants with different surface treatments: An experimental study in dogs Implant Dent. 2003;12:252–8
54. Muddugangadhar BC, Amarnath GS, Tripathi S, Dikshit S, Divya MS. Biomaterials for dental
implants: An overview Int J Oral Implantol Clin Res. 2011;2:13–24
55. Sykaras N, Woody RD, Lacopino AM, Triplett RG, Nunn ME. Osseointegration of dental
implants complexed with rhBMP-2: A comparative histomorphometric and radiographic evaluation Int J Oral Maxillofac
Implants. 2004;19:667–78
56. Park KH, Koak JY, Kim SK, Han CH, Heo SJ. The effect of ultraviolet-C irradiation via a bactericidal ultraviolet sterilizer on an anodized titanium implant: A study in rabbits Int J Oral Maxillofac
Implants. 2013;28:57–66
57. Meirelles L, Melin L, Peltola T, Kjellin P, Kangasniemi I, Currie F, et al Effect of hydroxyapatite and titania nanostructures on early
in vivo bone response Clin Implant Dent Relat Res. 2008;10:245–54
58. Nicu EA, Van Assche N, Coucke W, Teughels W, Quirynen M. RCT comparing
implants with turned and anodically oxidized surfaces: A pilot study, a 3-year follow-up J Clin Periodontol. 2012;39:1183–90
