|Year : 2016 | Volume
| Issue : 2 | Page : 85-91
Current trends in surface textures of implants
D Krishna Prasad, Archana Ashok Swaminathan, D Anupama Prasad
Department of Prosthodontics and Crown and Bridge, A B Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore, Karnataka, India
|Date of Web Publication||15-Mar-2017|
D Krishna Prasad
Department of Prosthodontics and Crown and Bridge, A B Shetty Memorial Institute of Dental Sciences, Nitte University, Deralakatte, Mangalore - 575 018, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Success of implant technology is due to several other factors such as biologic factors, local factors, and clinician and implant-related factors. Dental implant surface technologies have evolved rapidly in the recent times to enhance the bone formation on their surface. Following the placement of the implant, there is a predictable sequence of bone turnover and replacement at the interface that allows the newly formed bone to adapt to the implant surface. Chemical composition of the implant surface can differ markedly due to manufacturing, finishing, thermal treatment, blasting, etching, coatings, and even sterilization procedures. Based on these considerations, a careful control of implant surface composition becomes a relevant procedure to produce high-quality devices. This paper reviews the impact of various macrotopographical, microtopographical, and nanotopographical features at various stages of osseointegration and gauges the relative merits of various current innovations to the surface topography of titanium endosseous implants.
Keywords: Implant designs, implant surface treatments, nanotopography, photofunctionalized implants, sandblasted and acid-etched treatment, surface modifications
|How to cite this article:|
Prasad D K, Swaminathan AA, Prasad D A. Current trends in surface textures of implants. J Dent Implant 2016;6:85-91
| Introduction|| |
Dental implant is one of the most successful treatment modalities currently available for rehabilitating edentulous state. The key element in the success of implants is its ability of osseointegration as given by Brånemark in his theory of osseointegration. Brånemark et al. defined osseointegration at a light microscopic level as the direct structural and functional connection between ordered living bone and surface of a load-carrying implant. Reliable fixation of currently used endosseous dental implants relies primarily on mechanical interlock of bone and implant surface features at a microscopic and/or macroscopic level. Among the properties of titanium, one of the most important is the surface quality.
Dental implant surface technologies have evolved rapidly in the recent times to enhance the bone formation on their surface. Following the placement of the implant, there is a predictable sequence of bone turnover and replacement at the interface that allows the newly formed bone to adapt to microscopic roughness on the implant surface, and even a nanotopography has been shown to preferably influence the formation of bone. Chemical composition of the implant surface can differ markedly from bulk composition due to manufacturing, finishing, thermal treatment, blasting, etching, coatings, and even sterilization procedures. Based on these considerations, a careful control of implant surface composition becomes a relevant procedure to produce high-quality devices.
This paper reviews the impact of various macrotopographical, microtopographical, and nanotopographical features at various stages of osseointegration and gauges the relative merits of various current innovations to the surface topography of titanium endosseous implants.
| Stages of Osseointegration Influenced by Implant Body and Implant Surface Texture|| |
Surface modifications and design of implants are said to influence the osseointegration at various stages of healing [Figure 1].
|Figure 1: Healing stages affected by the surface topography and design of implants|
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The surgical process of implant dentistry requires initial fixation and lack of relative movement during the initial phases of the development of bone–implant interface. The implant design is of primary importance to accomplish this step. When implant design is cylinder, or bone quality is poor, the surface roughness of the implant will improve the surgical fixation of the implant.
Initial healing period
The initial healing period of an implant is the phase of osseointegration process that is primarily affected by the surface condition of the implant. As a general rule, roughened surfaces increase the bone–implant contact (BIC) percentage during the initial bone-healing process. However, the presence of smooth collar within bone or roughened collar at tissue levels does not have favorable results.
Early loading phase
The early loading period of an implant has considerations from an implant body design and surface condition of the implant, both similar in importance. BIC will directly relate to the amount of strain at the bone–implant interface.
When the strain conditions are within the physiologic zone of bone, the bone–implant interface may maintain a lamellar bone organization, which is organized and mineralized and is best to resist occlusal loads to the interface.
Implant design also may affect the early loading period of the implant. For example, smooth surface cylinder implants do not respond favorably to occlusal load. Smooth surface-threaded implants have early loading success, especially in good bone types.
Mature loading period
It occurs after 3–5 years and continues throughout the life span of the implant interface. Surface condition of the implant is least important during this phase.
| Levels of Surface Topography|| |
The surface modification of implants may be broadly divided into three categories depending on the level of surface modification, namely – macrotopography, microtopopgraphy, and nanotopography. At each level, the various modifications and the methods of obtaining it are discussed.
| Macrotopography|| |
This refers to the shape, outline of the implant body, the three-dimensional structure of the implant, the presence of threads, and other modifications.
One of the main macroscopic characteristics is the presence or absence of implant threads. When threads are present, they are usually double-threaded or triple-threaded. Again, according to their shape, the threads are subdivided as V-shaped, square, buttress, and reverse buttress.
Outline of the implant
There are various shapes of implants available, the most common being the tapered. Other outlines include stepped, conical, and paralleled. The apex of the implant also varies between flat, pointed, and rounded.
Further modifications include the incorporation of ledges, flutes, indentations, grooves, and vents.
| Microtopography|| |
As a general rule, an ideal implant biomaterial should present a microtopographical surface that will not disrupt, and that may even enhance, the general processes of bone-healing, regardless of implantation site, bone quantity, bone quality. As described by Ito et al., the approaches can be classified as physicochemical, morphologic, or biochemical.
This method mainly involves the alteration of surface energy, surface charge, and surface composition with the aim of improving the bone–implant interface. The method employed is glow discharge method which increases the cell adhesion properties and is conducive to tissue integration. However, it has been found that it does not help in adhering selective cells and it has not been shown to increase bone–implant interfacial strength.,
These methods are an adjunct to physiochemical and morphological methods. It utilizes the current understanding of biology and biochemistry of cellular function and differentiation.,,
The goal of biochemical surface modification is to immobilize proteins, enzymes, or peptides on biomaterial for the purpose of inducing specific cells and tissue response or in other words to control the tissue implant interface with molecules delivered directly to the interface.
Two main approaches to achieve this goal are as follows:
First approach is to control cell-biomaterial interaction utilizing cell adhesion molecules. A particular sequence, i.e., Arg-Gly-Asp (RGD), has been known as mediator of attachment of cells to several plasma and extracellular matrix proteins including osteopontin, bone sialoprotein, and fibronectin. Researchers are working toward incorporating this particular sequence onto implant to modulate the interface.
Second approach mainly deals with the biomolecules with demonstrated osteotropic effects. Molecules such as interleukin, growth factor 1 and 2, platelet growth factor, and BMP are known to have this effect.
This refers to the alteration of surface morphology and roughness to influence cell and tissue response to implants. Many animal studies support that bone in growth into macrorough surfaces enhances the interfacial and shear strength. It increases the BIC by the increase in the surface area of the implant, and it prevents the epithelial down growth on dental implants.
Two categories of surface characteristics that commonly cited for determining tissue response are:
- Surface topography/morphological characteristics
- Surface chemistry/chemical topography.
| Surface Topography: Methods and Surfaces|| |
Surface topography can be classified as:
- Sykaras N et al., have classified implant surfaces as:
- Minimally rough (0.5–1 µm)
- Intermediately rough (1–2 µm)
- Rough (2–3 µm).
- Based on texture obtained
- Concave texture (mainly by additive treatments such as hydroxyapatite [HA] coating and titanium plasma spraying)
- Convex texture (mainly by subtractive treatment such as etching and blasting).
- Based on orientation of irregularities 
- Isotopic surfaces: It has the same topography independent of measuring direction
- Anisotropic surfaces: It has clear directionality and differs considerably in roughness.
| Methods of Increasing Surface Roughness|| |
Various methods of increasing the surface roughness are as follows [Figure 2]:
It was the most commonly used surfaces in the past. It became decontamination only after turning process. Microscopic observation reveals the presence of a slight roughness because of the grooves and ridges produced during turning process. The ideal roughness for a turned surface was suggested to be 0.9–1.3 µ.
Blasting with particles of various diameters is one of the frequently used methods of surface alteration. It is mainly done by Al2O3 and TiO2 with particle size ranging from small, medium, to large grit. Roughness depends on particle size, time of blasting, pressure, and distance from the source of particle to the implant surface.
It allows adhesion, proliferation, and differentiation of osteoblasts. It also removes surface contaminants and increases surface reactivity of the metal. Cells located on the rougher surfaces are seen to remain for a longer time in proliferative state before further differentiation.
Blasting procedures leave residual particles on the surface of the implant and this could modify the bone-healing process. Some authors believe that the presence of Al2O3 particles remaining may be beneficial to osseointegration, catalyzing this process; whereas other authors believe that aluminum ions may impair bone formation by a possible competitive action to calcium.
Blasting a surface with titanium dioxide was proposed to promote a modification on the implant using a component of the oxide layer naturally formed around the implants.
Metallic implants are immersed into an acidic solution which erodes its surface creating pits of specific diameter and shape. Factors determining the result of chemical attack and microstructure of the surface:
- Concentration of acidic solution
It proposed to modify the implant surface without leaving the residues found after the sandblasting procedures. It helps to avoid the nonuniform treatment of the surface and to control the loss of metallic substance from the body of the implant. Baths of hydrochloric acid (HCl), sulfuric acid (H2 SO4), hydrofluoric acid (HF), and HNO3 are used in different combinations.
Roughness before etching, the acid mixture, the bath temperature, and the etching time all affect the acid-etching process.
Researchers compared etched surfaces with turned surfaces by inserting implants in rabbit femurs. The roughened surfaces were characterized by an “even distribution of very small (1–2 µ) peaks and valleys.” The resistance to torque removal was found to be 4 times that of turned surfaces.
Dual acid-etched technique
It produces a microtextured instead of macrotextured surface, which could be more predisposed to achieve desirable results. This is because of higher adhesion of platelet genes and higher expression of extracellular genes was observed in this dual acid-etched surfaces.
Sandblasted and acid-etched
Surface is produced by a large grit 250–500 µ blasting process, followed by etching with HCl/H2 SO4. Sandblasting results in surface roughness, while on the other hand, acid etching leads to microtexture and cleaning. Better bone integration as compared to the rest of the surfaces has been stated. It has gained popularity.
Resultant surface was constituted by uniformly scattered gaps and holes, which was a favorable environment for cell spreading. This type of surface tends to promote greater osseous contact at earlier time points compared with plasma sprayed, coated implants. They also provide better osteoconductive properties and a higher capability to induce cell proliferation than plasma-sprayed surfaces.
These implants are prepared by spraying molten metal on the titanium base, which results in a surface with irregularly sized and shaped valleys, pores, and crevices, increasing the surface area by 6–10 times.
This improves fixation by growth of bone into the coating forming a mechanical interlock.
Detachment of titanium occurs after implant insertion. Franchi et al. investigated the detachment of particles around plasma-sprayed, sandblasted, and acid-etched and turned implants. Fourteen days after placement, titanium debris was seen only in plasma sprayed samples. This could be related to the friction between implant surface and host bone cavity during implant placement, but the implications are not clear.
Oxidation process can be used to change the characteristic of oxide layer and make it more biocompatible. This is done by applying a voltage onto the titanium implant immersed in electrolyte. It results in surface with micropores with variable diameter and demonstrates lack of cytotoxicity and increased cell attachment and proliferation.
HA coating was brought to dental profession by De Groot et al.
It has similar roughness and increase in functional surface area as titanium plasma spray. A direct bone bond shown with HA coating and strength of HA to bone interface is greater than titanium to bone and even greater than titanium plasma spray to bone. Gap healing is enhanced by the HA coating. The corrosion rate of metal is also reduced, which is more significant for cobalt-chrome alloys. It is indicated in Type 4 bone, freshly extraction sockets, and newly grafted sites.,, Disadvantages include the delamination of coating leading to failure of implant, dissolution/fracture of HA coating resulting in failure, and predisposition to plaque retention.
| Various Methods of Coating|| |
Pulsed laser deposition
It is the latest method of coating HA onto an implant surface. Pulsed laser deposition is a thin film deposition technique where a high power pulsed laser beam is focused inside a vacuum chamber to strike a target of the material that is to be deposited. This material is vaporized from the target (in a plasma plume) which deposits it as a thin film on a substrate This process can occur in ultra-high vacuum or in the presence of a background gas, such as oxygen.
In a vacuum chamber, atoms or molecules of material are ejected from a target by bombardment of high energy ions. The dislodged particles are deposited on a substrate also placed in a vacuum chamber. There are various sputtering techniques such as diode sputtering ion sputtering, radiofrequent/direct current sputtering, magnetron sputtering, and reactive sputtering. All these techniques are variant of above-mentioned physical phenomenon.
It is the process by which a thin layer of HA can be coated onto an implant substrate. This is done by directing a beam of ion onto an HA block which is vaporized to create plasma and then recondensing this plasma on to implant. The bond strength between the layer and the substrate increased steadily with increasing current, while the dissolution rate decreased remarkably.
Radio frequency sputtering technique
This technique involves the deposition of HA in thin films. Studies have shown that these coatings are more retentive and chemical structure is precisely controlled. The other major advantage of this technique is that the design of implant particularly threaded implant is maintained.
This technique shows strong HA titanium bonding associated with outward diffusion of titanium into HA layer forming TiO2 at an interface.
Functionally graded coating
The main disadvantage of plasma spraying coating is the delamination. However, this disadvantage is overcome by the use of HA along with Ti6Al4V. The coating becomes mechanically strong, bioinert, and biocompatible.
Gentamycin along with the layer of HA can be coated onto the implant surface. Gentamycin acts as a local prophylactic agent along with the systemic antibiotics in dental implant surgery.
Laser ablation technique
To control the morphology of coating of HA, i.e., either crystalline or amorphous, this technique is best suited.
| Nanotopography|| |
The advent of obtaining the surface roughness of 1–100 nm gave way to the introduction of nanotopography of implants.
There are many methods to attain nanotopography of the implant surface. The physical approach involved compacting nanosized particles of titanium dioxide onto metal core by ion beam deposition. It is also achievable through a chemical approach, by the deposition of sol-gel (colloidal particle) of calcium phosphate, aluminum, zirconia and other materials.
Discrete crystalline deposition which superimposes nanoscale topography can be achieved via lithography and other optical methods. Biomimetic also play a role in nanotopography. This occurs through alkali treatment and anodization.
| Surfaces of Commonly Marketed Implants|| |
- Dentsply-Friadent: The friadent plus implant surface (Dentsply-Friadent) is manufactured by large grit blasting (354–500 μm) and acid etching in HCl/H2 SO4/HF/oxalic acid and finally neutralized with a proprietary process of Dentsply-Friadent.
- Ankylos implants: Both photoelastic studies and finite-element stress analyses have confirmed that the Ankylos special thread design reduces the functional stresses at the cervical section (crestal bone) compared with other implant systems. The thread portion of the implant is grit blasted to produce a rough surface.
- OsseoSpeed (Astra Tech AB, Mölndal, Sweden): The OsseoSpeed surface (Astra Tech AB) possesses 50–100 nm structured features created by titanium oxide blasting, followed by chemical modification of the surface by hydrofluoric acid treatment.
- TiUnite (Nobel Biocare Holding AG, Zürich, Switzerland): The TiUnite implant surface (Nobel Biocare Holding AG) is manufactured by anodic oxidation process to modify machined surfaces. It has been shown that this electrochemical anodization process increases the surface microtexture and changes the surface chemistry.
| Discussion on the Current and Future Trends|| |
As with every other field, various milestones have been crossed in advancements in surface technologies.
One of the many concerns in implant dentistry is the crestal bone loss that occurs, irrespective of the mucosal, crestal, or submerged placement of implants. Laser-Lok microchannels is a series of cell-sized circumferential channels that are precisely created using laser ablation technology. This technology produces extremely consistent microchannels that are optimally sized to attach and organize both osteoblasts and fibroblasts. Altering implant surface topography through precisely configured laser-ablated microgrooves (Laser-Lok, BioHorizons) adjacent to the IAJ appears to reduce the interimplant crestal bone loss often seen at inter-implant distances of <3 mm.
Ultraviolet (UV) light treatment of titanium implants has been reported to increase BIC from 55% to a near maximum level of 98.2% in an animal model. The increased BIC resulted in a threefold increase in the strength of bone–implant integration. The effectiveness of UV treatment in challenging conditions such as bone-healing with short implants and a significant peri-implant gap has also been demonstrated.
These photofunctionalized titanium surfaces display superhydrophilicity and substantially enhanced osteoconductivity and improved early osseointegration capabilities, which can be attributed to chemical alterations within the TiO2 coating.
A recent study proposed a new implant-mediated drug delivery system (IMDDS), in which the titanium implant is hollow and has multiple microholes that can deliver therapeutic agents into systemic body. Drug delivery using IMDDS allowed a constant release of the drug without any apparent lag phase for a long period.
| Conclusion|| |
Patients never ask for implants, only for rehabilitation of their edentulous state. Hence, the knowledge of the benefits and limitations of various implant surfaces, designs and systems are vital for arriving at a clear clinical decision on how to utilize the patient's oral presentation to give them the best rehabilitation possible.
Different implant surface treatments seem to influence the outcome of dental implants but the magnitude and clinical relevance of this influence are still being investigated. Clinician should consider the fact that even if several new surface treatments have been proposed, only long-term results and rigorous studies can eventually prove its efficacy. However, it is important to emphasize that the surface condition of an implant is not the only requirement to ensure long-lasting success.
In the end, it is important to remember that the success of the treatment on the skill of the operator to use the various modifications in accordance with the situations to obtain maximum benefit for the patient.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Brånemark PI, Zarb GA, Albrektsson T. Tissue-integrated Prostheses: Osseointegration in Clinical Dentistry. Chicago: Quintessence; 1985.
Stanford CM. Surface modifications of dental implants. Aust Dent J 2008;53 Suppl 1:S26-33.
Misch CE. Contemporary Implant Dentistry. 3rd
ed. St. Louis: Mosby Elsevier; 2007.
Hermann JS, Cochran DL, Nummikoski PV, Buser D. Crestal bone changes around titanium implants. A radiographic evaluation of unloaded nonsubmerged and submerged implants in the canine mandible. J Periodontol 1997;68:1117-30.
Sykaras N, Iacopino AM, Marker VA, Triplett RG, Woody RD. Implant materials, designs, and surface topographies: Their effect on osseointegration. A literature review. Int J Oral Maxillofac Implants 2000;15:675-90.
Gupta A, Dhanraj M, Sivagami G. Implant surface modification: review of literature. The Internet Journal of Dental Science 2008;7:7 pages.
Ito Y, Kajihara M, Imanishi Y. Materials for enhancing cell adhesion by immobilization of cell-adhesive peptide. J Biomed Mater Res 1991;25:1325-37.
Puleo DA, Thomas MV. Implant surfaces. Dent Clin North Am 2006;50:323-38, v.
Puleo DA. Biochemical surface modification of Co-Cr-Mo. Biomaterials 1996;17:217-22.
Lumbikanonda N, Sammons R. Bone cell attachment to dental implants of different surface characteristics. Int J Oral Maxillofac Implants 2001;16:627-36.
Anselme K. Osteoblast adhesion on biomaterials. Biomaterials 2000;21:667-81.
Yoshinari M, Oda Y, Ueki H, Yokose S. Immobilization of bisphosphonates on surface modified titanium. Biomaterials 2001;22:709-15.
Wennerberg A, Albrektsson T. Suggested guidelines for the topographic evaluation of implant surfaces. Int J Oral Maxillofac Implants 2000;15:331-44.
Rompen E, Domken O, Degidi M, Pontes AE, Piattelli A. The effect of material characteristics, of surface topography and of implant components and connections on soft tissue integration: A literature review. Clin Oral Implants Res 2006;17 Suppl 2:55-67.
Brunette DM. The effects of implant surface topography on the behavior of cells. Int J Oral Maxillofac Implants 1988;3:231-46.
Cochran DL, Nummikoski PV, Higginbottom FL, Hermann JS, Makins SR, Buser D. Evaluation of an endosseous titanium implant with a sandblasted and acid-etched surface in the canine mandible: Radiographic results. Clin Oral Implants Res 1996;7:240-52.
Aparicio C, Gil FJ, Planell JA, Engel E. Human-osteoblast proliferation and differentiation on grit-blasted and bioactive titanium for dental applications. J Mater Sci Mater Med 2002;13:1105-11.
Wennerberg A, Albrektsson T, Andersson B. Bone tissue response to commercially pure titanium implants blasted with fine and coarse particles of aluminum oxide. Int J Oral Maxillofac Implants 1996;11:38-45.
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.
Klokkevold PR, Johnson P, Dadgostari S, Caputo A, Davies JE, Nishimura RD. Early endosseous integration enhanced by dual acid etching of titanium: A torque removal study in the rabbit. Clin Oral Implants Res 2001;12:350-7.
Franchia M, Bacchellia B, Martinia D, De Pasqualea V, Orsinia E, Ottania V, et al
. Early detachment of titanium particles from various different surfaces of endosseous dental implants. Biomaterials 2004;25:2239-46.
Zhu X, Chen J, Scheideler L, Reichl R, Geis-Gerstorfer J. Effects of topography and composition of titanium surface oxides on osteoblast responses. Biomaterials 2004;25:4087-103.
de Groot K, Geesink R, Klein CP, Serekian P. Plasma sprayed coatings of hydroxylapatite. J Biomed Mater Res 1987;21:1375-81.
Ducheyne P, Van Raemdonck W, Heughebaert JC, Heughebaert M. Structural analysis of hydroxyapatite coatings on titanium. Biomaterials 1986;7:97-103.
Manley MT, Koch R. Clinical results with the hydroxyapatite-coated Omnifit hip stem. Dent Clin North Am 1992;36:257-62.
Denissen HW, Kalk W, Velhduis MH, van den Hooff A. Eleven years of study of hydroxyapatite implants. J Prosthet Dent 1989;61:706-12.
Yoshinari M, Watanabe Y, Ohtsuka Y, Dérand T. Solubility control of thin calcium-phosphate coating with rapid heating. J Dent Res 1997;76:1485-94.
Blind O, Klein LH, Dailey B, Jordan L. Characterization of hydroxyapatite films obtained by pulsed-laser deposition on Ti and Ti-6Al-4V substrates. Biomaterials 2005;21:1017-24.
Jansen JA, Wolke JG, Swann S, Van der Waerden JP, de Groot K. Application of magnetron sputtering for producing ceramic coatings on implant materials. Clin Oral Implants Res 1993;4:28-34.
Yoshinari M, Ohtsuka Y, Dérand T. Thin hydroxyapatite coating produced by the ion beam dynamic mixing method. Biomaterials 1994;15:529-35.
Ong JL, Bessho K, Cavin R, Carnes DL. Bone response to radio frequency sputtered calcium phosphate implants and titanium implants in vivo
. J Biomed Mater Res 2002;59:184-90.
Wolke JG, van Dijk K, Schaeken HG, de Groot K, Jansen JA. Study of the surface characteristics of magnetron-sputter calcium phosphate coatings. J Biomed Mater Res 1994;28:1477-84.
Kangasniemi IM, Verheyen CC, van der Velde EA, de Groot K.In vivo
tensile testing of fluorapatite and hydroxylapatite plasma-sprayed coatings. J Biomed Mater Res 1994;28:563-72.
Clèries L, Martínez E, Fernández-Pradas JM, Sardin G, Esteve J, Morenza JL. Mechanical properties of calcium phosphate coatings deposited by laser ablation. Biomaterials 2000;21:967-71.
Mendonça G, Mendonça DB, Aragão FJ, Cooper LF. Advancing dental implant surface technology – from micron- to nanotopography. Biomaterials 2008;29:3822-35.
Nevins M, Nevins M, Gobbato L, Lee HJ, Wang CW, Kim DM. Maintaining interimplant crestal bone height via a combined platform-switched, Laser-Lok implant/abutment system: A proof-of-principle canine study. Int J Periodontics Restorative Dent 2013;33:261-7.
Aita H, Hori N, Takeuchi M, Suzuki T, Yamada M, Anpo M, et al.
The effect of ultraviolet functionalization of titanium on integration with bone. Biomaterials 2009;30:1015-25.
Funato A, Yamada M, Ogawa T. Success rate, healing time, and implant stability of photofunctionalized dental implants. Int J Oral Maxillofac Implants 2013;28:1261-71.
Park YS, Cho JY, Lee SJ, Hwang CI. Modified titanium implant as a gateway to the human body: The implant mediated drug delivery system. Biomed Res Int 2014;2014. Article ID: 801358, 6 pages. Available from: http://dx.doi.org/10.1155/2014/801358
[Figure 1], [Figure 2]