Superficies y oseointegración (1)

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Modern dental implantology began almosthalf a century ago. A review of the currentliterature shows great evolution not only onimplant design and surgical techniques, butalso on the classification of clinical success,failure and different surface treatments [1–3].

Brånemark coined the term ‘osseointegration’, which defines success and failure of dentalimplants [4]. Osseointegration was originallydefined at the light microscopic level as “adirect structural and functional connectionbetween ordered, living bone and the surfaceof a load-carrying implant” [4]. Later, a moreclinically oriented definition was devised forosseointegration as a process in which clini-cally asymptomatic rigid fixation of alloplasticmaterials is achieved and maintained in boneduring functional loading. According to this

revised definition, “clinical osseointegrationimplies histologic osseointegration, it is neces-sary [there is] a contiguous contact between thealveolar bone and the implant surface” [5]. Theconventional protocol proposed by Bränemarkfor treatment with dental implants establishesthat implant procedures should be carried outin two phases. In the first, the ‘surgical phase’,the alveolus is prepared and the implant isinstalled. Furthermore, during the ‘prostheticphase’, the prosthesis is molded, prepared andinserted. A 3-month interval between the sur-

gical and prosthetic phase is recommended to

allow proper healing of mandibular implant whereas a 6-month interval is required for maillary implants. During the healing period, tpatient may experience discomfort and, in somcases, installation of provisional prosthesbecomes difficult.

Primary stability and a healing time 3–6 months before loading have been cosidered essential to allow osseointegration dental implants [6]. However, the need of thealing time to load a dental implant was nscientifically determined, but was only a clincal observation. Consequently, the originBränemark protocol has been modified ovthe years. Today, there are protocols descriing installation conditions with early implaloading or even immediate implant loadin[7]. Immediate implant loading is defined

an implant loaded within the first 24–48 after surgical implant placement, whereas earloading has been defined as loading performless than 14 days after the surgical implaplacement [8]. Previous results suggest ththere is no difference in implant failure rabetween early and conventional implant loaing [9]. Changes in the implant protocol cabe attributed to the improvement of surgicprocedures, biomechanical understanding the implants, modifications of the impladesign and development of new surface trea

ments to obtain optimal biological response

Carlos Nelson Elias† and Luiz Meirelles† Author for correspondenceInstituto Militar de Engenharia,Biomaterials Laboratory, Pr. Gen.Tiburcio 80, 22290-270 Rio de Janeiro, RJ, BrazilTel.: +55 212 546 [email protected]

In the beginning of implantology, the procedures adopted for treating patients were performein two surgical phases with an interval of 3–6 months. Nowadays, it is possible to insert anload a dental implant in the same surgical procedure. This change is due to several factors, sucas improvement of surgical technique, modifications of the implant design, increased quality implant manufacturing, development of the surgical instruments’ quality, careful patiescreening and adequate treatment of the implant surface. The clinical results show that adequatreatment of surfaces is crucial for reducing healing time and treating at-risk patients. The surfa

properties of dental implants can be significantly improved at the manufacturing stage, affectincells’ activity during the healing phase that will ultimately determine the host tissue responsa fundamental requirement for clinical success. This review focuses on different types of dentimplant surfaces and the influence of surface characteristics on osseointegration.

KEYWORDS: bone formation • dental implant • nanostructure • osseointegration • surface properties

Improving osseointegration of

dental implantsExpert Rev. Med. Devices 7(2), 241–256 (2010)


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Expert Rev Med Devices 7(2) (2010)242

Review Elias & Meirelles

titanium implants. To submit implants to masticatory load itis necessary to take into consideration that the body requires aminimum time to promote reactions leading to osseointegra-tion. The strategy consists of altering titanium implant surfaceproperties, modifying the surgical technique and selecting the

most adequate implant design for a given situation. The implantdesign has an influence on both primary stability and load dis-tribution, and there is no standardization of implant shapes.FIGURE 1 shows examples of avai lable dental implants with differ-ent designs. Among the various designs, the original cylindricalscrewed implants with an external hexagon are still largely in useafter approximately 50 years of clinical success.

The osseointegration of dental implants is critically depen-dent on their surface properties. Several investigations haveanalyzed the influence of implant surface properties for osseo-integration [10–15] . It has been shown that surface morphology,topography, roughness, chemical composition, surface energy,

chemical potential, strain hardening, the presence of impu-rities, thickness of titanium oxide layer and the presence ofmetal and non-metal composites have a significant influence onbone tissue reactions. The goal is to improve tissue response,decreasing the conventional waiting time for implant loadingand allowing immediate-early loading protocols. However, thebone–implant interface of immediate-early loaded implantsmust have similar mechanical strength compared with theinterface of a dental implant restored by the conventional pro-tocol, where the host tissue has 3–6 months of healing time andthe bone biomineralization process is likely to be completed,resulting in a tissue strong enough to resist oral forces. Allbiomaterials trigger biological responses from the body when

they are implanted. During implant insertion and further celladsorption on the material surface, cells activate mechanismsthat can identify the material chemical composition and inducedifferent reactions. There are three classes of biocompatiblematerials: bioinert, bioresorbable and bioactive [16]. With bio-inert materials (e.g., stainless steel, cobalt–chromium alloy,zirconium, aluminum and polyamides), the organism inducesformation of fibrous-tissue capsules surrounding the foreignbody (scar tissue). Bioresorbable materials dissolve in contact

with body fluids, such as polyglycolic acid and poly-l-lacticacid. Bioactive materials stimulate a biological response fromthe body, such as bonding to tissue. Hench and Jones sug-gested that there are two classes of bioactive materials: osteo-conductive and osteoproductive [16]. Osteoconductive materials

(e.g., synthetic hydroxyapatite [HA] and tricalcium phosphate)bond to hard tissue. Osteoproductive materials stimulate thegrowth of new bone on the biomaterial surface (una lloyed tita-nium and tantalum) and spontaneously bind to living bone ifthey have been previously subjected to a treatment involving asoak in NaOH solution, followed by a subsequent heat treat-ment. Therefore, these metals can be called bioactive metals [17].Bioactive materials a re those that elicit positive bone response, which could ultimately results in bone growth. They can bindto bone through a bone-like apatite layer on the implant surface, where a chemical bonding along the bone–implant interfaceis observed. There are similar biomaterial classifications dis-

cussing the different aspects of biomaterial cell–tissue interac-tion [18,19]. According to Yan, biomaterial may be described byrepresenting the tissues responses: biotolerant (e.g., stainlesssteel and polymethyl-methacrylate ), bioinert (e.g., aluminaand zirconia) and bioactive (e.g., tricalcium phosphate and bio-glass) [19]. Biotolerant materials release substances in nontoxicconcentrations, which may lead to the formation of a fibrousconnective tissue capsule. Bioinert materials exhibit minimalchemical interactions with adjacent tissue, and a fibrous capsulecan form around bioinert materials.

Osseointegration of dental implants

Osseointegration was defined initially as a direct bone-to-

implant contact and later considered, on a more functionalbasis, as a direct bone-to-implant contact under load [6]. Inthese definitions, the dynamic cellular and acellular processesthat occur at the interface on the micro- or nano-scale levelare not elucidated. Albrektsson et al. highlighted six factorsthat are especially important for the establishment of reliableosseointegration: implant material, implant design, surfaceconditions, status of the bone, surgical technique and implantloading conditions [20].

Osseointegration can occur only if the cells adhere to the bio-material surface. At this phase, reorganization of the cytoskeletonand information exchange between cells and the extracellular

matrix at the cell–biomaterial interface occur, generating geneactivation and specific tissue remodeling. Both the morphologyand roughness of the biomaterial’s surface have an influence oncell proliferation and differentiation, extracellular matrix syn-thesis, local factor production and even cell morphology [10]. Adhesion of osteoblasts onto implant surfaces is not enough toensure osseointegration; it is necessary for cells to receive signalsinducing them to proliferate. For example, coating the titaniumsurface with bone morphogenic protein-2 induces osteoblasticcell division after adhesion. The presence of fibronectin dur-ing the interaction between these cells and the implant surface,or the presence of protein, increases the cell division of human

osteoblasts. This phenomenon is associated with the fact that

Figure 1. Examples of commercially available dentalimplant designs.


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www expert reviews com 24

ReviewImproving osseointegration of dental implants

fibronectin has an amino acid sequence (RGD) signaling activa-tion of cell cycles, resulting in cell division of osteoblasts [21,22].Silva and Menezes cited that the success in the integration ofbiomaterial implants depends on responses such as cell attachmentand cell adhesion [23]. Cell adhesion must be regarded as a condi-

tion sine qua non for the effective application of the modern bio-engineering, particularly in those cases that involve implantationof 3D matrices colonized by the patient’s own cells. Therefore,one should analyze adsorption, adhesion and behavior of cellson the implant surfaces in order to speed up cell division, whileseeking to prevent apoptosis or cell death during contact withimplant surface.

During the initial healing phases, the complex 3D structureof the fibrin network with attached adhesive proteins provides asubstrate for cell adhesion and migration [24]. The compositionand conformation of proteins adsorbed on surfaces provide sig-nals or ligands for the adhesion of cells. The protein film on the

biomaterial surface has an influence on the adjacent host tissue, which may lead to changes in coagulation time, cell absorptionand tissue repair [24].

Interaction between cells & the surface of the

dental implants

Implant surface morphology affects attachment, proliferation,extracellular matrix synthesis, growth factor release and cyto-kine production. Boyan et al. analyzed the role of material sur-faces in regulating bone and cartilage cell response [21]. Initialevents at the surface include the adsorption of molecules fromthe surrounding fluid, creating a conditioned interface to whichthe cell responds. The surface morphology, as well as the micro-

topography and chemistry, determines the cell adsortion andhow cells will attach and align themselves [21]. It was suggestedthat distinct alterations in cell adhesion structures related tothe surface topography are responsible for differences in cellsignaling, which lead to changes in cellular functions, such asmineralization [25]. The attachment mechanisms used by thecells on the biomaterial surface determine cell shape, whichis transmitted via the cytoskeleton to the nucleus, resultingin expression of specific phenotypes. Insertion of biomaterialsinto the human body and their contact with body fluids trig-gers several events. The body fluids contain ions, as well aslipids, carbohydrates and proteins, that can be adsorbed at the

biomaterial surface. In this process, proteins play an importantrole in inducing the desired response. In the past, it was thoughtthat cells identifying the presence of a foreign body inducedinflammatory reactions that resulted in encapsulation of thebiomaterial, thus isolating the organism. Today, it is possibleto select the desired protein reaction by choosing the correctbiomaterial and treating the biomaterial’s surface. It is also pos-sible to obtain adsorption of a specific type of cell, or even avoidadhesion of organic material. For example, the surface of dentalprosthetic components may have properties controlling biofilmformation. In a similar way, the surfaces of dental implantsshould allow specific proteins to be adsorbed in order to trigger

the mechanisms of osseointegration [26].

After the initial protein reaction to the foreign body at the phyological level, the ensuing responses are controlled by a sequenof events that lead to acceptance or rejection of the material. Theresponses involve recruitment of various types of cells existinat the material’s surface, all accounting for activities such as t

remodeling of the extracellular matrix [27]. With regard to dentimplants, it is not desirable for cell recruitment to lead to encapslation of the material and consequent isolation from body fluidChanges in the implant surface, as well as control of both load anmicromovements, are crucial for preventing formation of fibrotissue at the bone–implant interface. The commercially pure titnium implant under overloading and higher micromovement donot present any osseointegration.

Based on the concepts above, one can conclude that the surfatopography is one of the key parameters influencing cellular reations towards artificial materials. The properties of dental implasurfaces are extremely important for controlling the reactio

that lead to osseointegration and optimal implant performancSurfaces with defined microstructures may be useful for enhancment of the stable anchorage of transcutaneous implants in conective tissue or for prevention of epithelial down growth ansubsequent exfoliation [28]. The surface morphology modulatthe response of cells to a dental implant [29–31]. These observatiosuggest that specific interactions of bone cells with the implasurface will result in altered phenotypic expression [32].

Surface properties, such as morphology, roughness, oxide laythickness, impurity level and oxide types, depend on the treatmeprocess of the implants. The difficulty in analyzing the individuinfluence of these parameters stems from the impossibility of alteing only one parameter without affecting others. For instanc

it is not viable to modify the type or chemical composition ancrystal structure of titanium oxide while keeping the roughneunchanged. When an implant is inserted into a tissue it woube expected to create an adhesive gradient [32]. Irrespective of ttype of implant material, a general sequence of inflammatory anrepair events take place in the surrounding tissue after implanttion [33]. After implant insertion, the surface comes immediateinto contact with blood. When in contact with the physiologicenvironment or blood plasma, titanium absorbs molecules, factI, factor III, IgG and CIq. A few seconds after the insertion, is possible to find platelets and polymorphonuclear granulocytadhered to the titanium surface. Adhesion of mature granul

leukocytes, neutrophils, acidophils and basophils occurs lateThe polymorphonuclear granulocytes are the first leukocytes be recruited to adhere to the titanium surface. Depending on tpreparation of the surface, there is a difference in cell adsorptioand reaction caused by the titanium exposed to human blood [3

The adhesion of monocytes (mononuclear leukocytes chaacterized by high phagocytic activity, representing 3–7% the circulating leukocytes) is sensitive to the thickness of thtitanium oxide layer [30]. Polymorphonuclear granulocytes amore dependent on the surface roughness of the implant, wheremacrophages prefer smoother surfaces.

A few months after insertion, treated implants show a great

amount of bone tissue covering their surface compared wi


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machined implants. Despite this finding, it is not clear how theimplant surface promotes or inhibits osteogenesis. It is possiblethat a successful implantation depends on how quickly osteo-genesis occurs around the implant – that is, rapid adhesion ofosteoblasts to the surface of the implant and extracellular matrix

synthesis. So far, there are not enough data regarding how theinitial osteoblast adhesion occurs; cell behavior depends on bothinteraction and triggering activities by cells and molecules.

Biomaterials in contact with the biological environmentexperience dynamic changes in their surface properties, whichinvolve a cascade of reactions at the interface between host andbiomaterial, thus forming a ‘conditioning film’ that modulatescell responses [34]. Cells possess mechanical receptive propertiescapable of identifying whether the implant surface has adequatecharacteristics favoring the initial process of differentiation andformation of bone matrix. The proteins adhering to implant sur-faces induce adsorption of osteoblastic and pre-osteoblastic cells.

Studies show that surface treatments change interface forces, wet-tability, roughness, energy and capacity of adsorption of moleculesthat recognize osteoblasts [30]. Cell adhesion is one of the initialevents, and is essential to subsequent proliferation and differen-tiation of bone cells before bone tissue formation [35]. It has beendemonstrated that cell adhesion to the surrounding extracellu-lar matrix can influence many fundamental cellular processes,including cell growth and differentiation [36].

Wettability and surface energy influence the adsorption of pro-teins, and increase osteoblast focal adhesion on the implant surface.The cell behavior on a hydrophilic surface is completely differentfrom that on a hydrophobic one. The expressions of bone-specificdifferentiation factors for osteoblasts, such as type I collagen and

osteoprotegerin, are higher on hydrophilic surfaces [37]. Cells onhydrophilic surfaces may generate an osteogenic environment byproducing more cytokines, such as TGF-1 and PGE-2. Animalresearch compared hydrophilic with hydrophobic dental implants with equally rough surfaces. The results showed that a hydrophilicsurface presents a significantly higher bone-to-implant contact at 2and 4 weeks of healing compared with a hydrophobic surface [38].

A study analyzed and compared differences in the initial adhe-sion of osteoblasts on two groups of titanium substrates differingonly in surface energy. The results showed that higher implantsurface energy enhances cellular adhesion owing to wettability;more cells bind directly to the surface [39]. Understanding the

influence of surface topography and chemical functionality onthe growth and adhesion of cells to biomaterials is importantfor improving tissue–implant interfacial strength. Ismail et al. analyzed the influence of surface chemistry and topography onthe contact guidance of MG63 osteoblast cells [40]. When bonecells are attached to a solid substrate, their behavior and functiondepends on the physicochemical and morphological properties ofthe biomaterial surface. These surface characteristics determinehow biological molecules will adsorb on the surface and, moreparticularly, determine the orientation of adsorbed molecules [41].

The insertion of dental implants in low-density bone is a prob-lem and the probability of failure increases during the treatment.

An example is the treatment of patients with a systemic disorder,

such as osteoporosis, or after being exposed to radiotherapy.Patients submitted to irradiation demand new approaches toimplant osseointegration [42]. Such circumstances imply a chal-lenging bone healing situation. Under these conditions, the sur-vival rate of dental implants may decrease. The development of

surface modifications may increase the success of dental implantsin compromised patients. Patients with medical conditions, suchas diabetes, radiation treatment for cancer, xerostomia and osteo-porosis, do not exhibit the optimum bone conditions for placementof dental implants and the establishment of osseointegration.

Implant surface topography

Although commercially pure titanium is the prime material of dentalimplants, there is a different rate of success among available dentalimplant systems. The exact explanation of the difference betweensuccess or failure among commercial implants is not clear. The pro-cess of osseointegration depends on several factors and is not yet fully

understood. The effect of implant surface topography, chemicalcomposition and surface roughness on the process of bone forma-tion are the most studied factors. Studies have shown that titaniumimplants with adequate roughness may enhance bone-to-implantcontact [43] and may increase removal torque force [44–46].

In addition, the roughness of implant surfaces also affectsthe primary stability of dental implants [47]. Some mechanismsinvolved in the osseointegration vary depending on whether theimplant surface is smooth or rough, since cells react differentlyto these conditions. Fibroblasts and epithelial cells adhere morestrongly to smooth surfaces, whereas osteoblastic proliferation andcollagen synthesis are increased on rough surfaces [48].

Several authors have tried to quantify the influence of roughness

on osseointegration in order to obtain optimal surface conditions[11,13,49]. Despite the importance of roughness for osseointegration,there is no ideal pattern of roughness regarding dental implants.Buser et al. observed a tendency for increased bone-to-implantcontact with increasing implant surface roughness [50]. Londonet al. could not confirm this observation [51]. Another study sug-gested that only dental implants with Ra value between 1 and1.5 µm induce an optimal surface for bone integration, so-calledmoderately rough implants [52].

In T ABLE 1, one can observe that Ra has a significant influence onthe torque needed to remove the implant. Other parameters areused to quantify the degree of roughness, such as quadratic aver-

age roughness (Rq), peak to valley roughness (Rz), and maximumroughness height (Rmax). Among the space descriptive param-eters used were highest peak (Rpkx), highest valley (Rvkx), peakarea (A1) and valley area (A2). Although the parameter Ra willnot always be useful to characterize the morphology of a givensurface, it has been used because no other variable of roughnessis known to better describe and predict the implant behavior.Doubts exist as to whether the height of surface irregularitiesis more important than the distance between them, and whichcombination of these factors could improve osseointegration.

Although the increase in surface roughness promotes greatermechanical anchorage, the implant–bone interface strength will

not increase with the continuous increase of surface roughness


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values. Wennerberg et al. analyzed machined and Al2O

3-blasted

implants (particles sized 25 and 250 µm) [53]. They observed abetter bone response for implant blasted with 25-µm particlescompared with an as-machined surface (MS); however, no differ-ences were found between the implant blasted with 25-µm par-

ticles (Ra = 0.82 + 0.2 µm) and the implant blasted with 250-µmparticles (Ra = 2.11 + 0.1 µm). Additionally, implants blasted with 25-µm particles of Al

2O

3 exhibited a greater bone–implant

contact area (46.4%) compared with those blasted with 250-µmparticles (39.2%), despite the lower Ra values. The results indi-cated that there is an optimal range regarding surface roughnessfor bone formation, and an average height deviation parameterbetween 1 and 2 µm is recommended for dental implants [54].

Takeuchi et al. [55] and Brunette [32] have observed that the mor-phology and composition of a surface affect both shape and functionof the cells. The cell shape regulates growth, gene expression, proteinsecretion, differentiation and apoptosis, while increased roughness

influences differentiation of osteoblasts and osteoclasts[32]

.Osteoblasts become flattened on smooth surfaces and they tendto grow towards the machined grooves (FIGURE 2). Grooves havinga depth of 0.5 µm and a width ranging from 4.9 to 200 µm allowcells to grow along them. This cell behavior is different for sur-faces exhibiting homogenous roughness. Cells present haptotaxis,rugophobia and rugopholy. Regardless of the situation, there isno direct contact between implant surface and bone because ofthe existence of a thin layer of adsorbed proteins (fibronectin andvitronectin) [56].

The production of extracellular matrix is sensitive to rough-ness. Cell proliferation on implant surfaces is different becausethe cells can identify rough surfaces. Cells cultivated on a rough

surface increase production of osteocalcin and alkaline phospha-tase. These parameters are, therefore, indicative of osteoblasticdifferentiation and consequent increases in osteoblast number [48].Production of growth factors, such as TGF-1, is increased onrough surfaces, and this is known to stimulate collagen formationand prostaglandin production. There is a relationship betweenosteogenic differentiation and increases in both roughness andproduction of PGE-1 and -2 [48]. Inhibition of prostaglandin pro-duction depends on a decrease in cell proliferation and an increasein phenotypic expression, as well as on the production of TGF-1, which suggests that the production of prostaglandin involved withthe mechanism of surface roughness depends on the stimulation

of osteogenic differentiation [29].

Nanotopography

Nanotopography modifications are commonly described in tliterature both as nanoroughness and nanofeatures. It is importato understand that the overall surface roughness of the sample wbe modified when features are added to the surface, that is, b

adding nanofeatures the surface roughness will also be modifieMoreover, the nanorough material will also possess nanofeaturehowever, the modifications commonly used to produce the scalled nanorough materials (e.g., acid etching) did not intetionally produce such nanofeatures, and from the usual surfaroughness parameters alone in use, is not possible to evaluate tdimension of each individual feature at the surface. By contrasnanofabricated samples have well-defined dimensions that aito modulate cell activity, such as migration, attachment, proleration and differentiation. FIGURE 3 shows an example of dentimplant surface submitted to a nanotopography modification.

Nanoroughness

Webster et al. evaluated osteoblast adhesion in vitro on almina and titania discs prepared by compacting powders widifferent sized particles onto the surface [57]. The discs wesintered at different temperatures to obtain different nanroughness parameters of alumina and titania. Higher osteoblaadhesion was observed on both alumina and titania discs wiincreased mean root square deviation (S

q) and larger surfa

area. Additionally, discs prepared with an identical methoconsisting of Ti, Ti

6 Al

4 and CoCrMo was tested. As previous

reported on alumina and titania discs, increased osteoblaadhesion was found on the discs from the different grou with increased mean root square deviation [58]. Webster et ainvestigated osteoblast adhesion and concentration of differeproteins adsorbed on alumina, titania and HA, with diffeent nanoroughnesses [59]. Pore diameter and porosity (%) wealso calculated. Once again, the osteoblast adhesion was greaton the discs that exhibited increased nanoroughness, indepedently of the surface chemistry. Surface porosity was higher anpore diameter decreased in discs with increased nanoroughneProtein adsorption revealed a greater amount of vitronectassociated with increased osteoblast adhesion on the roughdiscs. Osteoblast proliferation and alkaline phosphatase sythesis on these surfaces was evaluated in another study from tsame group; alkaline phosphatase synthesis was higher after

and 28 days on the discs with increased nanoroughness value

Table 1. Dental implant roughness and torque required to remove from rabbit’s tibia.

Surface Ra (µm) Rq (µm) Rz (µm) Rmax(µm)

Rpkx (µm) Rvkx(µm)

A1 (µm2) A2 (µm2) Torque(N.cm)

Machined 0.65 ± 0.11 0.81 ± 0.17 6.09 ± 0.37 7.76 ± 1.37 21.6 ± 0.41 3.14 ± 0.52 24.71 ± 5.42 70.66 ± 16.20 57.0 ± 18

Acid etched 0.51 ± 0.10 0.71 ± 0.07 5.09 ± 0.46 6.78 ± 1.33 1.77 ± 0.37 2.74 ± 0.42 34.76 ± 7.35 103.86 ± 14.80 75.4 ± 10

Sandblasted 0.75 ± 0.05 0.98 ± 0.04 5.55 ± 0.21 12.44 ± 9.7 6.75 ± 0.76 9.91 ± 1.71 99.75 ± 6.76 190.13 ± 4.90 72.1 ± 14

Anodized 0.87 ± 0.14 1.12 ± 0.18 5.14 ± 0.69 19.84 ± 2.13 16.71 ± 2.47 6.25 ± 1.23 97.67 ± 11.43 215.37 ± 1.67 83.1 ± 12.

A1: Peak area; A2: Valley area; Ra: Roughness average; Rmax: Maximum roughness height; Rpkx: Highest peak; Rq: Quadratic average roughness; Rvkx: Highestvalley; Rz: Peak to valley roughness.Data taken from [13].


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De Oliveira and Nanci cultured bone rat calvaria cells on tita-nium discs etched with H

2SO

4 and H

2O

2[60]. They observed

that the acid-etched surface revealed nanopits, whereas the con-trol failed to show such features, although the surface roughness was not numerically evaluated. The results indicated an overex-pression of osteopontin and bone sialoprotein, both intra- andextra-cellularly, on cells seeded on the nano-modified group. Inaddition, a higher proportion of cells with peripheral cytoplasmicdistribution of osteopontin were observed as early as 6 h.

Larlsson et al. evaluated turned plus anodized, electropolished,and electropolished plus anodized implants on a rabbit modelafter 1–6 weeks [61]. The electropolished implant investigated withatomic force microscope (AFM) showed the smoothest surface. After 6 weeks, the electropolished implants showed decreasedbone formation compared with the rougher implants. In an identi-

cal study, similar implants were investigated after 7–12 weeks ofhealing [62]. After 7 weeks, the results were similar to the previ-ous study, which indicated higher bone formation to implants with increased surface roughness values (anodized) compared with the smooth implants (electropolished). After 12 weeks, thevalues for the rough implants were steady and the values for theelectropolished implants increased to approximately the same levelas that found for the rougher implants. Long-term evaluation ofthese implants for 1 year did not reveal any difference in boneformation [63]. It is concluded by in vitro and in vivo experimentsthat cell activity and bone healing may be optimized by modulat-ing surface roughness on the nanometer level of resolution.

Nanofeatures

The literature cited in the following section includes nanofeaturemodifications that exhibit at least one dimension below 100 nm.The first commonly investigated design with controlled dimen-sions on the surfaces was the paral lel groove and ridge arrange-ment at the microscale [32]. Cell orientation was related to thegroove/ridge, and this phenomenon was described as contactguidance. Approximately 10 years later, cell activity was alsorelated to nanofeatures. Wojciak-Stothard et al. investigatedmurine macrophages on flat and nanogrooved surfaces withdifferent depth [64]. By 15 min after plating, most cells remained

in the vicinity of the plain substrata, compared with well-spread

cells observed on the nanogrooved sub-strata, which indicates cell activation.Moreover, cell adhesion increased gradu-ally from plain substrata with shallow(30 nm) grooved substrata to higher values

observed on deeper (282 nm) grooved sub-strata. Similar results were found for cellorientation; the deeper the grooves, themore orientated the cells became. Anotherapproach to optimize cell activity withnanofeatures includes the so-called islands[65] or hemispherical pillars [66] obtained bythe polymer demixing process or colloidallithography. Dalby et al. compared fibro-blast activity on flat surface and surface

with 13-nm high islands with a diameter of 263 nm [65]. After3 days, increased fibroblast spreading, more focal contacts asso-

ciated to vinculin, upregulation of genes involved with cell sig-naling and collagen precursors were observed on the surface withnanoislands compared with the flat surface. In another study,endothelial cell activity was tested on surfaces with islands withheights of 13, 35 and 95 nm [67]. Similar to fibroblasts, endothe-lial cells on the surface with 13-nm islands exhibited the largestcell areas (longer and wider axes) and well-defined cytoskeletons,compared with the flat, and the 35- and 95-nm surface islands.Contrary to the increased activity of the fibroblast and endo-thelial cells, surfaces with similar features (18-, 35- and 95-nmislands) did not influence rat calvaria bone cells [68]. In a recentpaper, by Dalby et al., cell activity was compared on surfaces with different nanofeatures, including 35- and 45-nm islands

with diameters of 2.2 and 1.7 µm, respectively [69]. Features with columns 10-nm high and 144-µm in diameter were alsoadded on the flat (control) substrata. The human bone marrowcells showed increased cell spreading in the three groups, withcells extending filopodia towards the nanofeatures. It also dem-onstrated a well-defined cytoskeleton, enhanced expression ofstress fibers with clear focal contacts and increased expression ofosteocalcin and osteopontin on the substrata with nanofeatures.

Mendes et al. demonstrated higher bone formation withnano-CaP coated cpTi and Ti6Al4V compared with uncoatedcpTi and Ti6Al4V groups placed in rats [70]. Nano-CaP features were analyzed by field-emission scanning electron microscopy, and

the size varying from 20–100 nm was estimated by high magnifica-tion analysis of the samples. Similar implant surface modification with nano-CaP was also evaluated in a human study. Goéne et al. placed microimplants into human posterior maxilla, and higherbone contact was observed to nano-CaP-coated compared withuncoated implants after 4 and 8 weeks of healing [71].

In a series of studies, nanostructures of different sizes and chem-ical composition were evaluated both on smooth and moderatelyrough implants inserted in a rabbit model [72]. Turned cylindricalsmooth implants were electropolished or mechanically polished tocontrol the effect of microstructures, that is the bone response eval-uated depended only on the nanomodification. In one experiment,

electropolished implants were compared with electropolished

10 µm20 µm

Figure 2. Surface morphology influences the osteoblast shape.


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implants modified with nano-HA [73]. AFM characterizationrevealed an increase of 7 nm in size and 5 nm in diameter of thedetected nanofeatures present at the nano-HA surface, and similarfeature density compared with electropolished implants; whileboth nano- and micro-roughness were similar. After 4 weeks of

healing, significantly higher bone formation was observed aroundthe nano-HA implant. Later, in an identical model, nano-HA andnano-titania implants were compared for 4 weeks, an alternativeto differentiate the influence of nanometer features and chemicalcomposition [74]. AFM characterization showed larger features with remarkably lower density on the nano-HA surface compared with the nano-titania. Histological analyses demonstrated a ten-dency for enhanced bone formation to nano-titania compared with nano-HA implants. The influence of nanofeatures was alsoevaluated on moderately rough screw-shaped implants [75]. Themoderately rough blasted implant group was the control groupof the experiment and the underlying substrate for the two test

groups included in the experiment: nano-HA modified and acid-etched with fluoride. Field-emission scanning electron microscopeanalysis revealed particular nanofeatures at the fluoride-treatedand nano-HA implants, whereas the blasted implants failed toshow such small features. The microroughness analysis with aninterferometer showed similar values (surface roughness [Sa]1.3 µm). After 4 weeks, screw-shaped moderately rough implantsthat exhibited particular nanostructures showed higher removaltorque values compared with blasted control implants that lackedsuch structures. The presence of nanostructures, irrespective ofvarying surface chemistry, resulted in evidence of supported boneformation. The next step for continuous development of biomate-rial surfaces may focus on the ideal nanostructure dimension and

distribution at the implant surface [72].

Influence of the implant surface morphology

on osseointegration

Doubts exist about the optimal procedure for obtaining the bestbiological response to dental implants. When the importance theimplant surface properties have for osseointegration is analyzed,one should separate the influence of implant design and the mor-phology of surface. Analysis of implant design involves dimen-sions (length, diameter and wall thickness), shape (cylindrical,conical and hybrid), screw thread type (triangular, squared, trape-zoidal, rounded, microscrew and grooved), paths of screw threads,

angle of screw threads and type of prosthesis connection (e.g.,external hexagonal, internal hexagonal connection, Morse coneand star grip). Some of those parameters influence the primarystability [47] and mechanical strength of the implant. With regardto the surface morphology, one should analyze the macro-, micro-,and nano-structures, as well as the surface homogeneity, chemicaland physical properties, type of oxide and its crystal structure.

Dental implant surface modification

Several techniques to modify the implant surface have been pro-posed to improve the success rate of oral rehabilitation with osseo-integrated implants [13,38,49,76–86]. The results provide guidelines

for the development of implant surfaces.

The differences between commercially available implants cinvolve roughness, chemical composition, surface energy, chemicpotential, presence of hydrates and nitrates, layer with residual streimpurities resulting from manufacturing or handling proceduretype of titanium oxide, crystal structure of oxide and thickness

oxide layer. Analysis of these differences is important, as proteiinteract with the oxides existing on implant surfaces. The surfaroughness of dental implants can be assessed at three scales: maroscopically, microscopically and nanoscopically [87]. Each rougness determines different contacts with cells and biomolecules, thbeing responsible for intensity and types of biological bonds indvidually. Initially, one could expect that increasing the surface arof the implant should result in more sites for cell attachment, facitating tissue growth and improving mechanical stability. Howevthis is not a general rule and may vary depending on the cell typFibroblasts avoid rough surfaces and accumulate on smooth oneOn the other hand, macrophages exhibit rugophilia, that is, th

prefer rough surfaces, whereas epithelial cells are more attracted rough surfaces than to smooth ones. Osteoblastic cells adhere rough surfaces more easily, a finding also observed in commerciaavailable implants with chemically treated surfaces [27,56,88].

Besides the surface topography and roughness, surface chemistry has been investigated. Chemical composition of the surfahas an influence on the secondary stability and reactivity of thimplant. Schneider et al. reported the effect of surface chemiston the cell behavior of osteoblasts using a variety of cell cutures and animal models [89]. Schwarz et al. analyzed the effecof surface hydrophilicity and microtopography on early stagof soft- and hard-tissue integration at nonsubmerged titaniuimplants [90]. The results indicated that titanium surfaces wi

a higher surface energy may possess higher potency to promodifferentiation of osteoblasts by a higher expression of cell dferentiation and cell activity markers, such as ALP, OC and TII. Their results confirm data from other authors [91,92].

The morphology of dental implant surfaces may be modified chemical, mechanical, electrochemical and laser beam treatmenBy treating the implant surface, it is possible to reduce the loadin

Figure 3. Example of dental implant surface submitted tonanotopography modification.


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time following surgery [49], accelerate bone growth and matura-tion [44], increase primary stability [47] and ensure a successfulimplantation [2]. There are numberless variables, combinationsof parameters related to surface treatment and factors influencingosseointegration (material, implant design, implant surface, bone

quality and quantity, surgical technique and loading conditions).However, researchers have established no consensus on whichsurface, roughness and even implant design would be optimal.

The manufacturers adopt a variety of techniques for treatingimplant surfaces. Such treatments increase the implant surfacearea, improve primary stability, modify wettability, increase thebone-to-implant contact area and increase the bone–implantinterface strength.

Selection of the methodology to be used for implant surface treat-ment is initiated by choosing the desirable roughness, since macro-,micro- and nano-roughness are differently achieved. Today, there is atendency of obtaining hybrid surfaces morphologically characterized

by micro- and nano-structures[72,75]

.In some cases, the manufacturers change the chemical com-position of the implant surfaces by adding calcium, phosphorusand fluoride [80,93].

Nowadays, the dental implant surface modifications can beimparted by different methods, including ion beam, laser etch-ing, acid etching, anodization and biomimetic coatings. Forstudy purposes, the surface modifications can be divided intoseven groups: machined, plasma spray and laser, acid etching,grit blasting follow acid etching, laser etching, anodizing andbiomimetic coatings.

Machined dental implants

Machined or turned implants were used in early implantology,introduced by Brånemark [4]. After being manufactured, theseimplants are submitted to cleaning, decontamination and steriliza-tion procedures. Scanning electron microscopy analysis shows thatthe surfaces of machined implants have grooves, ridges and marksof the tools used for their manufacturing (FIGURE 4). These surfacedefects provide mechanical resistance through bone interlocking.

The disadvantage regarding the morphology of nontreatedimplants (machined) is the fact that osteoblastic cells are rugo-philic – that is, they are prone to grow along the grooves existingon the surface, as shown in FIGURE 2. This characteristic requiresa longer waiting time between surgery and implant load-

ing. The use of these implants follows a protocol suggested byBrånemark: 3–6-month healing or waiting time prior to loading.

Owing to morphological characteristics and lower resistance toremoval torque (T ABLE 1), machined dental implants are becomingcommercially unavailable.

Plasma spraying & laser treatments

An alternative surface treatment is laser ablation and plasma spray-ing a metal or ceramic onto an implant’s surface. The surfacetreatment processes using laser and plasma spraying induce highvalues for roughness parameters, which may be characterized asmacrorugosities. FIGURE 5 shows the morphology of the implant sur-face treated with laser. The surface exhibits macroroughness at lowmagnification, whereas melting structures can be observed at highmagnification. At higher magnification, a laser-treated surface issmoother than others. Interestingly, surfaces with layers deposedby plasma spraying have similar characteristics, macroroughnessand melting structures.

Plasma spraying and laser treatments are no longer being used,

because the resulting macrorugosities have greater effects on pri-mary stability than secondary stability. It is expected that surfacecharacteristics exhibit biological influence during implant instal-lation and interaction with cells by modifying the mechanismsinvolved in cell adsorption and differentiation.

The osseointegration of the dental implant with plasma-sprayedHA is faster than uncoated implants. However, studies haveshown that these coatings may be partially dissolved/resorbedafter long periods of function [94]. In addition, the HA coatingis chemically unstable and bonds weakly to the implant surface.Considering the potential of the association between laser abla-tion and smaller scale HA coatings to create a stable and bioactivesurface on titanium dental implants, Faeda et al. analyzed theeffects of a surface treatment created by laser-ablation (neodym-ium-doped yttrium aluminum garnet [Nd:YAG]) and, later, thindeposition of HA particles by a chemical process [95]. They com-pared the removal torque of implants treated with laser followedby acid etching, implants with only laser-ablation and implants with MS. After 4, 8 and 12 weeks of healing, the removal torque was measured. Average removal torque in each period was 23.3,24.0 and 33.9 Ncm to MS, 33.0, 39.9 and 54.6 Ncm to laser-modified surface (LMS), and 55.4, 63.7 and 64.0 Ncm to HA.The difference was statistically significant (p < 0.05) betweenthe LMS-MS and HA-MS surfaces in all periods of evaluation,and between LMS-HA to 4 and 8 weeks of healing. The surface

characterization showed a deep, rough and regular topographyprovided by the laser conditioning that was followed by the HA

coating. They conclude that the implants with laser surface modification associated with HA biomimetic coating can shortenthe implant healing period by the increaseof bone implant interaction during the first2 months after implant placement [95].

Acid-etched dental implants

Every manufacturer has its own acid-etching method regarding concentration,

time and temperature for treating implant

100 µm 100 µm 20 µm

Figure 4. Machined dental implant surface morphology. It is possible to observetool irregularities from the machining process.


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surfaces. In general, acid treatment is performed by immersingthe implants into solutions of HCl + H

2SO

4, HF + HNO

3 and

HNO3. After acid attack, the implant is again immersed into anaqueous solution of HNO3 for passivation of titanium oxide and

formation of a stable oxide layer. An example of the morphologyof an acid-etched surface of a commercially available implant isshown in FIGURE 6.

Acid treatment provides homogeneous roughness, increasedactive surface area and improved bioadhesion. The morphologyof the implant surface shown in FIGURE 5 is isotropic and exhibitsmicro-cavities with defined edges. This type of surface not onlyfacilitates retention of osteogenic cells, but also allows them tomigrate towards the implant surface. Implants having surface mor-phology similar to that shown in FIGURE 5 induce fibrin retention,favor adsorption of fibronectin and facilitate osseointegration [96].

Despite the high success of dental implants with treated sur-faces, complications can occur, such as loss of integration, peri-implantitis and mucositis, prothesis screw loosening and fractureof the implant itself. FIGURE 7 shows the apical part of a dentalimplant fractured 4 years after the surgery. The broken implant was removed surgica lly and the implant presented acid etchingsurface morphology characteristics. The failure occurred after thehealing period due to implant overloading. The dental implantpresented a good osseointegration. Scanning electron microscopyobservations showed, in some areas, the presence of organic mate-n some areas, the presence of organic mate-rial, which was present directly on the implant surface.

Acid etching yields low surface energy

and reduces the possibility of contamina-tion since no particles are encrusted in thesurface. Among the commercially avail-able acid-treated implants, one can cite theMaster Porous System® (Conexão Sistemade Próteses, Brazil), Osseotite® (Biomet 3i,USA), Friadenty Plus® (Friadent GmbH,Germany), Defcon TSA ® (Impladent SL,Spain) and BlackFix ® (TitaniumFix, Brazil).

Blasted implants & etching

The atomic arrangement at the external sur-

face of bulk metallic materials is different in

terms of internal distribution. Atoms locatat the surface are surrounded by a smallnumber of neighbors compared with thoatoms in the inner regions, which increasthe level of atomic energy at the impla

surface. As a result, there is a greater tedency of adsorption of foreign atoms anmolecules. The greater the surface enerper unit area is, the greater the possibility reactions between body and material. Whthe implant is blasted, its surface suffers platic microdeformation, in which a layer wicompressive residual stress is created. Part the kinetic energy of the particles is stored the form of crystal defects, such as disloc

tions, twins and grain boundaries, and these modifications increathe material surface energy [97], as well as the possibility of mod

fication in the interaction between cells and implant. The residustress values obtained from blasting procedures depend on bohardness and granulometric distribution of the particles used. Tgreater the granulometric distribution, the more heterogeneous tstrain distribution. Although acid treatment after blasting removsome atomic layers of the titanium surface deformed by the blastinprocedure, part of the residual strain remains at the implant surfac

Surfaces with Ra equal to 1 µm have a good performance [1This level of roughness can be obtained by blasting followed bacid treatment (FIGURE 8 ). The blasting procedure allows controf the size of microcavities, but particles may be encrusted anthen contaminate the surface of the implant (FIGURE 7B).The gblasting or sandblasting technique is normally made with titan

or alumina. After the grit blasting procedure, performed particlremain on the surface of implants and must be removed with acand ultrasonic bath.

The influence of surface roughness on bone formation on titnium-blasted surfaces was evaluated [53]. The samples were blast with Al

2O

3 particles. After surface preparation, the samples we

passivated, washed with distilled water and dried. The resulfrom animal experiments showed higher values for removal torquand bone-to-implant contact for samples blasted with 25- an75-µm sized particles compared with those machined or blast with 250-µm particles.

10 µm5 µm

Figure 5. Dental implant surface treated with a laser. It is possible to observemacroroughness and morphology with melting characteristics.

20 µm3 µm

Figure 6. Typical dental implant surface morphologies with acid etching treatmenImage courtesy of Conexão Sistemas e Proteses, Brazil.


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Alumina particles in the size range 25–50 µm are used tosandblast the Sand-blasted, Large grit, Acid-etched (SLA™)implant (Straumann ITI, Germany). The sandblasting is fol-lowed by an acid etch in hot HCl/H

2SO

4 acid solution. These

processes create micropits superimposed on the rough-blastedsurface. The pits have an average diameter of 1 µm, and coalesceto form larger craters with an average diameter of 10 µm.Sandblasting surfaces have Ra equal to 1.19 µm and the totalroughness (Rt) equal to 10.53 µm. Jarmar et al. measured theroughness on SLA and Sa and found it to be 1.98 ± 0.08 µm [98].

The dental implant denominate TiOblast™ (Astra Tech AB,Sweden) made of commercially pure titanium is another exampleof a gritblasted and then acid-etched treated implant. TiOblastis gritblasted with 25-µm titanium oxide particles, which createsmall pits of predetermined size and shape.

The OsseoSpeed™ (Astra Tech AB, Sweden) dental implantsurface is fluoride-modified (hydrofluoric acid-treated surface).The implant surface is blasted and later etched with dilutedhydrofluoric acid, which slightly reduces the high peaks. Thefinal surface structure has an isotropic roughness – that is, thereis no preferred direction of the surface irregularities [93]. During

the blasting procedure, the surface roughness is increased. TheOsseoSpeed surface has Sa = 0.91 ± 0.14 µm and the TiOblastsurface has Sa = 1.12 ± 0.24 µm. The hydrofluoric acid treat-ment does not only change the microstructure, but also thesurface chemistry. According to the authors [93,99], the surfacefluoride incorporated in the oxide acts as a precipitation site forcalcium and phosphorus, and also allows covalent bonding tothe phosphate to create fluoridated HA and fluorapatite.

Anodized implants

Titanium has a high surface energy following the machiningprocedure, which facilitates adsorption of oxygen molecules.

Approximately 10 ns after oxygen adsorption, the molecules

dissociate to form the first atomic monolayer of oxygen. Theadsorbed oxygen transforms into titanium oxide within a fewmilliseconds. Therefore, direct contact between pure titaniumand the host bone is very unlikely because the presence of thetitanium oxide layer and the properties of titanium oxide are

more important in terms of biocompatibility than those of puretitanium. Based on this principle, researchers have modified boththe morphology and the crystal structure of the titanium oxideof the implant surfaces. One of the methods consists of increas-ing the thickness of the oxide layer by anodization. This can beachieved by several electrochemical procedures [13,44,100].

Anodization is an electrochemical process where the implant isimmersed in an electrolyte while a current is applied, which willmake the implant the anode in an electric cell. Commercial den-tal implants, such as TiUnite™ (NobelBiocare, Switzland) andVulcano Actives™ (Conexão Sistemas de Prótese, Brazil), areanozided. The electrolyte and the current used in the implants

treatment process create a porous surface structure(FIGURE 9)

.The high chemical stability and biocompatibility of titaniumare due the formation of titanium oxide on its surface. Titaniumoxide has three crystalline structures: anatase (tetragonal), rutile(tetragonal) and brookite (orthorhombic) [101]. Crystallinity willincrease as the oxide layer thickness increases. Rutile and anataseforms are the most important oxide structures for osseointegrationof implants. In addition to the increase in oxide layer thickness,the titanium oxide film obtained from electrochemical anod-ization incorporates calcium and phosphorus as a heritage fromthe electrolyte. The surface has more than 7% phosphorus inthe oxide layer, the highest percentage of amorphous hydroxidescompared with other implants assessed by x-ray photoelectron

spectroscopy (XPS). As a result, the titanium oxide existing onthe implant surface shows changes in its morphology and crystalstructure [102].

By characterizing anodized implant surfaces with x-ray dif-fraction, Raman and XPS, it was found that a predominance ofanatase forms on anodized surfaces compared with MS, wherethe rutile form is predominant (FIGURE 9A). The results showedthat the differences between commercial implants depend onthe method used for surface treatment. Blasted and acid-treatedsurfaces exhibit predominantly rutile forms, although their mor-phologies are different. On the other hand, anodized surfaceshave a predominance of anatase forms (FIGURE 10) and micropores

measuring 0.5–3.0 µm (FIGURE 9) . The XPS spectra indicate thatthe chemical composition of the outermost surface oxide layer onthe anodized implant surface contains calcium and phosphoruselectrochemically incorporated from the mixed electrolyte solu-tion during the oxidation process (FIGURE 10B).

The tissue healing process around anodized or acid etchedimplants, inserted in bone sites with and without defects, isquicker than in machined implants. In order to assess the effi-ciency of anodized implants, Gurgel el al. used dog teeth, and3 months after extraction, they produced defects measuring 5 mmhigh and 4 mm wide before inserting the implants [103]. The ani-mals were sacrificed 3 months after the implant insertion. The

researchers found that the percentages of bone-to-implant contact

25 µm

Figure 7. Apical part of broken osseintegrated dental

implant with acid etching treatment. The fracture occurred4 years after the surgery. It is possible to observe the adhesion oforganic material on the implant surface.


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and bone density of anodized implants were 57.03 ± 21.86% and40.86 ± 22.73%, whereas machined implants had 37.39 ± 23.33%

and 3.52 ± 4.87%, respectively.Sul et al. compared mechanical strength and osseous-con-ductivity of anodized implants containing magnesium, TiUnite(anodized) and Osseotite (double acid attack) [104]. The implants were inserted into rabbit tibia, and 3– 6 weeks later removaltorques and the percentage of bone-to-implant contact weremeasured. Magnesium implants demonstrated significantlygreater removal torque values and more new bone formationthan Osseotite at 3 and 6 weeks. Magnesium implants alsoshowed higher removal torque values at 3 weeks and new boneformation at 6 weeks than TiUnite. The results indicate thatsurface chemistry facilitated more rapid and stronger osseoin-tegration of the magnesium implants. This suggests potential

advantages of magnesium implants for reducing high implantfailure rates in the early postimplantation stage and in compro-mised bone, making it possible to shorten bone healing timefrom surgery to functional loading, and enhancing the possibilityof immediate/early loading. The anodized surface implant hasa higher polarity compared with that of acid-treated samples, which causes adsorption of water and molecules. Adsorption ofthese molecules creates an electric field along the oxide thickness.This electric field induces titanium oxidation and, at the sametime, the oxide layer thickness increases, thus decreasing bothpotential difference and the driving force for dissolution [104].In this way, taking into account that surface structure as well

as morphology are correlated with wettability, changes in theirproperties affect adsorption of proteins needed for cell adhe-sion on the implant surface. Consequently, the performance ofa given treated surface depends on the biological response of theimplants used.

Mechanisms of bioactive dental implants

Bioactive materials form bioactive bonding with the livingbone by growing an apatite layer on their surfaces after they areimplanted in the bony site [17,105] . Titanium oxide has a tendencyto adsorb water at the surface, resulting in the formation of tita-nium hydroxide groups. Experimental results showed that tita-

nium metal and its a lloys subjected to NaOH and heat treatments

exhibit an apatite-forming ability and intgrate with living bone. The apatite-formbone. The apatite-forming ability of the metal is attributed to tamorphous sodium titanate that is formduring the NaOH and heat treatment [10

The bioactivity of a material depends espcially on the structure and the amount functional groups such as amino (–NHand hydroxyl (–OH) groups. The preence of hydroxide groups on the surface implant materials plays an important ro with respect to biointeraction with bocells and can stimulate cell attachment the artificial hydroxyl-containing surfacIt was also observed that the basic titaniu

hydroxide groups induce apatite nucleation and crystallizatiin simulated body fluid. Titanium oxides derived using som

techniques, such as a sol-gel process and treatment of metaltitanium with H2O

2 or alkali, have abundant titanium hydroxi

groups on the surface, and bone-like apatite is formed on tsurface. However, the apatite is not biomimetically formed osingle crystal titanium oxide (anatase).

Conclusions

• Various processes exist to treat the surface of commerciaavailable implants. Most of these surfaces have been analyzby in vivo and in vitro studies, showing high clinical succerates. However, the methodologies used to prepare these sufaces are mostly empirical, requiring a great number of assayMoreover, the tests are not standardized and this makesdifficult to compare the results;

• The results from in vivo and in vitro studies show that the surfacharacteristics of the dental implants influence cell activity;

• The dental implant surface treatment influences the way ceadhere to the surface, which influences differentiation, proleration, differentiation and formation of extracellular matri

15 µm 10 µm

Figure 8. Typical titanium dental implant surface sandblasted. (A) Clean surface.(B) Surface with alumina particle contamination.

20 µm

Figure 9. Anodized dental implant surface morphology.


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• Topographic characteristics, roughness, energy and chemicalcomposition modify cell growth and change cell function atthe initial stages of osseointegration;

• Further studies are needed to improve and describe the inter-action between cells and implant surfaces, as well as to assessthe influence of different parameters involved, such as pro-teins, bone formation stimuli and individual therapy, forcompromised patients.

Expert commentary & five-year viewThe development of dental implant surfaces over the past yearshas improved oral rehabilitation in terms of patient inclu-sion criteria and overall tissue response. Bone and soft-tissueresponses to dental implants and attached prosthesis havebecome more predictable, fulfilling the higher expectationsfrom the patients and also f rom the dentists. There is a generalagreement regarding material selection and which elementsshould be avoided at the implant surfaces, reducing the possibil-ity of failures, despite the constant increase of inserted dentalimplants worldwide.

Current standards for surface characterization of dental

implant-related materials commonly focus on limited surfaceproperties and evaluation techniques that may not represent whathas really changed on the material surface. A so-called chemi-cal modification, for example, will probably add new structures

on the surface and, at the same time, change the wettability ofthe material. These three surface properties (among others) areknown to modify cell–tissue interactions. Thus, a specific surfaceanalysis protocol could be established, providing guidelines forfuture developments.

The recent focus on nano-based modifications has given oneextra alternative to improve tissue response. In addition, the pos-sibility to investigate the cell–tissue interaction on the nanoscale wil l provide results for better understanding the mechanismbehind implant success or failure. At this stage, it is difficult to

determine the ideal size and configuration of the nanostructuresfor dental implant surfaces, but preliminary results indicate thatsolely the presence of specific nanostructures will improve boneformation. The clinical follow-up of these modifications will indi-cate the potential benefits for the patients, with special attentionto tissue preservation and costs.

Financial & competing interests disclosure

The work was financially supported by the Brazilian Government (CNPqProcess 472449/2004-4, 400603/2004-7 e 500126/2003-6 and FAPERJ

Process E-26/151.970/2004). The authors have no other relevant affiliations

or financial involvement with any organization or entity with a financial

interest in or financial conflict with the subject matter or materials discussedin the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this

manuscript.

Raman shift cm-1100 200 300 400 500 600 700 800

0

250

500

750

1000

1250

1500

1750

2000

I n t e n s i t y

( a . u . )

1 4 6

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5 1 5 6

3 7

11001000 900 800 700 600 500 400 300 200 100 0

5

10

15

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Binding energy/eV

I n t e n s i t y / c o u n t s

• 1 0 0 0

•

0 K L L

• 0 1 s

• T 1 2 p

• C a 2 s

• C a 2 p

• C a L M M • C

K L L

+ C

1 s

• P 2 s

• P 2 p

• S 1 2 s

• S 1 2 p

• C a 3 p , 0 2 s

Figure 10. Anodized dental implant spectra. (A) Raman spectrum. (B) x-ray photoelectron spectroscopy spectrum.

Key issues

• Titanium dental implant success is increasing because the surgery technique has changed, implant manufacturing improved and implant

surface treatments are used.

• Titanium surface treatments change cell activities.

• Surface roughness changes the cells’ behavior.

• Dental implant surface treatment is essential to reduce the implant loading time, and for the treatment of patients with a systemic disorder.

• To improve the dental implant osseointegration, the surface treatment is the most important procedure.


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ReferencesPapers of special note have been highlighted as:• of interest

•• of considerable interest

1 Bartlett D. Implants for life? A criticalreview of implant-supported restorations.

J. Dent. 35(10), 768–772 (2007).

2 Creugers NH, Kreulen CM, Snoek PA,De Kanter RJ. A systematic review ofsingle-tooth restorations supported byimplants. J. Dent. 28(4), 209–217 (2000).

3 Pye AD, Lockhart DE, Dawson MP,Murray CA, Smith AJ. A review of dentalimplants and infection. J. Hosp. Infect. 72(2), 104–110 (2009).

4 Brånemark Pi, Hansson BO, Adell R et al. Osseointegrated implants in the treatmentof the edentulous jaw. Experience from a10-year period. Scand. J. Plast. Reconstr.

Surg. Suppl. 16, 1–132 (1977).

•• One of the first publicat ions presenting

the osseointegration concept as accepted

and applied today.

5 Brånemark PI, Adell R, Albrektsson T,Lekholm U, Lundkvist S, Rockler B.Osseointegrated titanium fixtures in thetreatment of edentulousness. Biomaterials 4(1), 25–28 (1983).

6 Brånemark PI, Zarb GA, Albrektsson T.Tissue-integrated prostheses: Osseointegrationin clinical dentistry. Quintessence, Chicago,IL, USA (1985).

7 Attard NJ, Zarb GA. Immediate and earlyimplant loading protocols: a literaturereview of clinical studies. J. Prosthet . Dent. 94(3), 242–258 (2005).

8 Chiapasco M. Early and immediaterestoration and loading of implants incompletely edentulous patients. Int. J. Oral Maxillofac. Implants 19(Suppl.), 76–91(2004).

9 Ioannidou E, Doufexi A. Does loadingtime affect implant survival? A meta-analysis of 1,266 implants. J. Periodontol. 76(8), 1252–1258 (2005).

10 Anselme K, Bigerelle M. Topographyeffects of pure titanium substrates onhuman osteoblast long-term adhesion. ActaBiomater. 1(2), 211–222 (2005).

11 Wennerberg A. The importance of surfaceroughness for implant incorporation. Int. J. Mach. Tool Manufact. 38(5–6), 657–662(1998).

12 Zhu X, Chen J, Scheideler L, Reichl R,Geis-Gerstorfer J. Effects of topographyand composition of titanium surface oxideson osteoblast responses. Biomaterials 25(18), 4087–4103 (2004).

13 Elias CN, Oshida Y, Lima JH, Muller CA.Relationship between surface properties(roughness, wettability and morphology) oftitanium and dental implant removaltorque. J. Mech. Behav. Biomed. Mater. 1(3), 234–242 (2008).

14 Tete S, Mastrangelo F, Traini T et al. A macro- and nanostructure eva luation of anovel dental implant. Implant. Dent. 17(3),309–320 (2008).

15 Zhang S, Yan L, Altman M et al. Biologicalsurface engineering: a simple system for cellpattern formation. Biomaterials 20(13),1213–1220 (1999).

16 Hench LL, Jones JR. Biomaterials ArtificialOrgans and Tissue Engineering. WoodheadPublishing Limited, Cambridge, UK (2005).

• Offers an overview of biomaterials for

beginners and advanced readers.

17 Kokubo T, Kim HM, Kawashita M,Nakamura T. Bioactive metals: preparationand properties. J. Mater. Sci . Mater. Med. 15(2), 99–107 (2004).

18 Osborn JF, Newesely H. Dynamic aspectsof the implant-bone-interface. In: DentalImplants. Heimke G (Ed.). Carl HanserVerlag, Munich, Germany 111–123 (1979).

19 Yan W. Nanocoating for orthopaedic anddental application. In: Nanocomposite ThinFilms and Coating: Processing, Properties andPerformance. Zhang S, Ali N (Eds).Imperial College Press, London, UK

573–588 (2007).

20 Albrektsson T, Brånemark PI, HanssonHA, Lindstrom J. Osseointegratedtitanium implants. Requirements forensuring a long-lasting, direct bone-to-implant anchorage in man. Acta Orthop.Scand. 52(2), 155–170 (1981).

21 Boyan BD, Hummert TW, Dean DD,Schwartz Z. Role of material surfaces inregulating bone and cartilage cell response.Biomaterials 17(2), 137–146 (1996).

22 Schliephake H, Aref A, Scharnweber D,Bierbaum S, Roessler S, Sewing A. Effect of

immobilized bone morphogenic protein 2coating of titanium implants on peri-implant bone formation. Clin. OralImplants Res. 16(5), 563–569 (2005).

23 Silva FC, Menezes GC. Osteoblastsattachment and adhesion: how bone cellsfit fibronectin-coated surfaces. Mat. Sci .Eng. C-Bio. S. 24(5), 637–641 (2004).

24 Anderson JM. Biologica l responses tomaterials. Annu. Rev. Mater. Res. 31,81–110 (2001).

25 Nebe B, Luthen F, Lange R, Becker P,Beck U, Rychly J. Topography-induced

alterations in adhesion structures affect

mineralization in human osteoblasts ontitanium. Mat. Sci . Eng. C-Bio. S . 24(5),619–624 (2004).

26 Lim JY, Liu X, Vogler EA, Donahue HJ. Systematic variation in osteoblast adhesioand phenotype with substratum surface

characteristics. J. Biomed. Mater. Res. A 68(3), 504–512 (2004).

27 Thull R. Physicochemical principles oftissue material interactions. Biomol. Eng. 19(2–6), 43–50 (2002).

28 Scheideler L, Geis-Gerstorfer J, Kern D et al. Investigation of cell reactions tomicrostructured implant surfaces. Mat. SEng. C-Bio. S. 23(3), 455–459 (2003).

29 Eisenbarth E, Velten D, Schenk-Meuser Ket al. Interactions between cells andtitanium surfaces. Biomol. Eng. 19(2–6),243–249 (2002).

30 Eriksson C, Lausmaa J, Nygren H.Interactions between human whole bloodand modified tio2-surfaces: influence ofsurface topography and oxide thickness oleukocyte adhesion and activation.Biomaterials 22(14), 1987–1996 (2001).

31 Hennessy KM, Pollot BE, Clem WC et aThe effect of collagen i mimetic peptideson mesenchymal stem cell adhesion anddifferentiation, and on bone formation athydroxyapatite surfaces. Biomaterials 30(10), 1898–1909 (2009).

32 Brunette DM. Principle of cell behaviour

on titanium surfaces and their applicationto implanted devices. In: Titanium in Medicine. Brunette DM, Tengvall P,Textor M, Thomsen P (Eds). SpingerVerlag, Berlin, Germany 485–512 (2001)

33 Holgers KM, Esposito M, Kalltorp M,Thomsen P. Titanium in soft tissue. In:Titanium In Medicine. Brunette DM,Tengvall P, Textor M, Thomsen P (Eds).Spinger Verlag, Berlin, Germany 513–560(2001).

34 Kanagaraja S, Alaeddine S, Eriksson C et aSurface characterization, protein adsorptioand initial cell-surface reactions onglutathione and 3-mercapto-1,2,-propanediol immobilized to gold. J. Biome Mater. Res. 46(4), 582–591 (1999).

35 Anselme K. Osteoblast adhesion onbiomaterials. Biomaterials 21(7), 667–681(2000).

•• Excellent review on cell–material

interactions, with special emphasis on

proteins associated to osteoblast adhesio

36 Damsky CH. Extracellular matrix-integrinteractions in osteoblast function andtissue remodeling. Bone 25(1), 95–96(1999).


14/17



37 Qu Z, Rausch-Fan X, Wieland M,Matejka M, Schedle A. The initialattachment and subsequent behaviorregulation of osteoblasts by dental implantsurface modification. J. Biomed. Mater. Res . A 82(3), 658–668 (2007).

38 Zollner A, Ganeles J, Korostoff J, Guerra F,Krafft T, Bragger U. Immediate and earlynon-occlusal loading of Straumannimplants with a chemically modifiedsurface (SLActive) in the posteriormandible and maxilla: Interim results froma prospective multicenter randomized-controlled study. Clin. Oral Implants Res. 19(5), 442–450 (2008).

39 Rupp F, Scheideler L, Olshanska N,De Wild M, Wieland M, Geis-Gerstorfer J.Enhancing surface free energy andhydrophilicity through chemical

modification of microstructured titaniumimplant surfaces. J. Biomed. Mater. Res . A 76(2), 323–334 (2006).

40 Ismail FS, Rohanizadeh R, Atwa S et al. The influence of surface chemistry andtopography on the contact guidance ofmg63 osteoblast cells. J. Mater. Sci . Mater. Med. 18(5), 705–714 (2007).

41 Walivaara B, Aronsson BO, Rodahl M,Lausmaa J, Tengvall P. Titanium withdifferent oxides: In vitro studies of proteinadsorption and contact activation.Biomaterials 15(10), 827–834 (1994).

42 Granstrom G. Radiotherapy,osseointegration and hyperbaric oxygentherapy. Periodontol 2000 33, 145–162(2003).

43 Wennerberg A. On Surface Roughness andImplant Incorporation (PhD thesis). Universityof Göteborg, Göteborg, Sweden (1996).

44 Sul YT, Johansson CB, Jeong Y, Wennerberg A, Albrektsson T. Resonancefrequency and removal torque analysis ofimplants with turned and anodized surfaceoxides. Clin. Oral Implants Res. 13(3),252–259 (2002).

45 Wennerberg A, Ektessabi A, Albrektsson T,

Johansson C, Andersson B. A 1-yearfollow-up of implants of differing surfaceroughness placed in rabbit bone. Int. J. Oral Maxillofac. Implants 12(4), 486–494 (1997).

46 Klokkevold PR, Nishimura RD, Adachi M,Caputo A. Osseointegration enhanced bychemical etching of the titanium surface. Atorque removal study in the rabbit. Clin.Oral Implants Res. 8(6), 442–447 (1997).

47 Dos Santos MV, Elias CN, Cavalcanti Lima JH. The effects of superficial roughness anddesign on the primary stability of dentalimplants. Clin. Implant Dent. Relat. Res.

(2009) (Epub ahead of print).

48 Boyan BD, Dean DD, Lohmann CH.The titanium bone cell interface in vitro: therole of the surface in promotingosteointegration. In: Titanium in Medicine. Brunette DM, Tengvall P, Textor M,Thomsen P (Eds). Springer Verlag, Berlin,

Germany (2001).49 Cochran DL, Schenk RK, Lussi A,

Higginbottom FL, Buser D. Bone responseto unloaded and loaded titanium implants with a sandblasted and acid-etched sur face:a histometric study in the canine mandible. J. Biomed. Mater. Res. 40(1), 1–11 (1998).

50 Buser D, Schenk RK, Steinemann S,Fiorellini JP, Fox CH, Stich H. Influence ofsurface characteristics on bone integrationof titanium implants. A histomorphometricstudy in miniature pigs. J. Biomed. Mater.Res. 25(7), 889–902 (1991).

51 London RM, Roberts FA, Baker DA,Rohrer MD, O’Neal RB. Histologiccomparison of a thermal dual-etchedimplant surface to machined, tps, and hasurfaces: bone contact in vivo in rabbits.Int. J. Oral Maxillofac. Implants 17(3),369–376 (2002).

52 Wennerberg A, Albrekts son T. Suggestedguidelines for the topographic evaluation ofimplant surfaces. Int. J. Oral Maxillofac.Implants 15(3), 331–344 (2000).

53 Wennerberg A, Albrekts son T, Andersson B. An animal study of cptitanium screws with dif ferent surfacetopographies. J. Mater. Sci . Mater. Med. 6(5), 302–309 (1995).

54 Albrektsson T, Wennerberg A. Ora limplant surfaces: Part 1 – review focusingon topographic and chemical properties ofdifferent surfaces and in vivo responses tothem. Int. J. Prosthodont. 17(5), 536–543(2004).

•• Guidelines for surface roughness

evaluation of dental implants.

55 Takeuchi K, Saruwatari L , Nakamura HK, Yang JM, Ogawa T. Enhanced intrinsicbiomechanical properties of osteoblasticmineralized tissue on roughened titaniumsurface. J. Biomed. Mater. Res . A 72(3),296–305 (2005).

56 Leduc P, Wang Y. Protein adsorption at thebiomaterial/tissue interface. In: AnIntroduction to Biomaterials. Guelcher SA,Hollinger JO (Ed.), The BiomedicalMaterials Series. CRC Taylor & FrancisGroup, Boca Raton, FL, USA, 47–61(2006).

57 Webster TJ, Siegel RW, Bizios R. Osteoblastadhesion on nanophase ceramics.Biomaterials 20(13), 1221–1227 (1999).

58 Webster TJ, Ejiofor JU. Increasedosteoblast adhesion on nanophase metals:Ti, Ti6Al4V, and CoCrMo. Biomaterials 25(19), 4731–4739 (2004).

59 Webster TJ, Ergun C, Doremus RH,Siegel RW, Bizios R. Enhanced functions

of osteoblasts on nanophase ceramics.Biomaterials 21(17), 1803–1810 (2000).

60 De Oliveira PT, Nanci A. Nanotexturing oftitanium-based surfaces upregulatesexpression of bone sialoprotein andosteopontin by cultured osteogenic cells.Biomaterials 25(3), 403–413 (2004).

61 Larsson C, Thomsen P, Aronsson BO et al. Bone response to surface-modified titaniumimplants: studies on the early tissueresponse to machined and electropolishedimplants with different oxide thicknesses.Biomaterials 17(6), 605–616 (1996).

62 Larsson C, Thomsen P, Lausmaa J,Rodahl M, Kasemo B, Ericson LE. Boneresponse to surface modified titaniumimplants: studies on electropolishedimplants with different oxide thicknessesand morphology. Biomaterials 15(13),1062–1074 (1994).

63 Larsson C, Emanuelsson L, Thomsen P et al. Bone response to surface modifiedtitanium implants – studies on the tissueresponse after 1 year to machined andelectropolished implants with differentoxide thicknesses. J. Mater. Sci . Mater. Med. 8(12), 721–729 (1997).

64 Wojciak-Stothard B, Curtis A, Monaghan W, Macdonald K, Wilkinson C. Guidanceand activation of murine macrophages bynanometric scale topography. Exp. Cell Res. 223(2), 426–435 (1996).

•• First publication of this group

demonstrating the cell response to

nanometer size structures. Many references

are available from this group in this field.

65 Dalby MJ, Yarwood SJ, Riehle MO, Johnstone HJ, Affrossman S, Cur tis AS.Increasing fibroblast response to materialsusing nanotopography: morphological andgenetic measurements of cell response to13-nm-high polymer demixed islands. Exp.Cell Res. 276(1), 1–9 (2002).

66 Andersson AS, Backhed F, Von Euler A,Richter-Dahlfors A, Sutherland D,Kasemo B. Nanoscale features influenceepithelial cell morphology and cytokineproduction. Biomaterials 24(20),3427–3436 (2003).

67 Dalby MJ, Riehle MO, Johnstone H, Aff rossman S, Curtis AS. In vitro reactionof endothelial cells to polymer demixednanotopography. Biomaterials 23(14),

2945–2954 (2002).


15/17



68 Riehle MO, Dalby MJ, Johnstone H,Macintosh A, Affrossman S. Cell behaviourof rat calvarial bone cells on surfaces withrandom nanometric features. Mat. Sci . Eng.C-Bio. S. 23(3), 337–340 (2003).

69 Dalby MJ, Mccloy D, Robertson M et al. Osteoprogenitor response to semi-orderedand random nanotopographies.Biomaterials 27(15), 2980–2987 (2006).

70 Mendes VC, Moineddin R, Davies JE.The effect of discrete calcium phosphatenanocrystals on bone-bonding to titaniumsurfaces. Biomaterials 28(32), 4748–4755(2007).

71 Goené RJ, Testori T, Trisi P. Influence of ananometer-scale surface enhancement onde novo bone formation on titaniumimplants: a histomorphometric study inhuman maxillae. Int. J. Periodontics

Restorative Dent. 27(3), 211–219 (2007).72 Meirelles L. On Nano Size Structures for

Enhanced Early Bone Formation. PhDThesis. Göteborgs University, Göterborgs,Sweden (2007).

73 Meirelles L, Arvidsson A, Andersson M,Kjellin P, Albrektsson T, Wennerberg A.Nano hydroxyapatite structures influenceearly bone formation. J. Biomed. Mater.Res. A 87(2), 299–307 (2008).

74 Meirelles L, Melin L, Peltola T et al. Effectof hydroxyapatite and titaniananostructures on early in vivo bone

response. Clin. Implant Dent. Relat. Res. 10(4), 245–254 (2008).

75 Meirelles L, Currie F, Jacobsson M, Albrekts son T, Wennerberg A. The effectof chemical and nanotopographicalmodifications on the early stages ofosseointegration. Int. J. Oral Maxillofac.Implants 23(4), 641–647 (2008).

76 Cooper LF, Zhou Y, Takebe J et al. Fluoride modification effects on osteoblastbehavior and bone formation at TiO

2

grit-blasted c.p. titanium endosseousimplants. Biomaterials 27(6), 926–936(2006).

77 De Assis AF, Beloti MM, Crippa GE,De Oliveira PT, Morra M, Rosa AL.Development of the osteoblastic phenotypein human alveolar bone-derived cells grownon a collagen type I-coated titaniumsurface. Clin. Oral Implants Res. 20(3),240–246 (2009).

78 Franco RL, Chiesa R, Beloti Mm,De Oliveira PT, Rosa AL. Humanosteoblastic cell response to a Ca- andP-enriched titanium surface obtained byanodization. J. Biomed. Mater. Res. A 88(4), 841–848 (2009).

79 Franco Rde L, Chiesa R, De Oliveira PT,Beloti MM, Rosa AL. Bone response to aCa- and P-enriched titanium surfaceobtained by anodization. Braz. Dent. J. 19(1), 15–20 (2008).

80 Granato R, Marin C, Suzuki M, Gil JN,

Janal MN, Coelho PG. Biomechanical andhistomorphometric evaluation of a thin ionbeam bioceramic deposition on plateauroot form implants: an experimental studyin dogs. J. Biomed. Mater. Res . B Appl .Biomater. 90(1), 396–403 (2009).

81 Guo J, Padilla RJ, Ambrose W, De Kok IJ,Cooper LF. The effect of hydrofluoric acidtreatment of TiO

2 grit blasted titanium

implants on adherent osteoblast geneexpression in vitro and in vivo. Biomaterials 28(36), 5418–5425 (2007).

82 Mendonca G, Mendonca DB, Simoes LG

et al. The effects of implant surfacenanoscale features on osteoblast-specificgene expression. Biomaterials 30(25),4053–4062 (2009).

83 Mendonca G, Mendonca DB, Simoes LG et al. Nanostructured alumina-coatedimplant surface: effect on osteoblast-relatedgene expression and bone-to-implantcontact in vivo. Int. J. Oral Maxillofac.Implants 24(2), 205–215 (2009).

84 Monjo M, Lamolle SF, Lyngstadaas SP,Ronold HJ, Ellingsen JE. In vivo expressionof osteogenic markers and bone mineraldensity at the surface of fluoride-modifiedtitanium implants. Biomaterials 29(28),3771–3780 (2008).

85 Tavares MG, De Oliveira PT, Nanci A,Hawthorne AC, Rosa AL, Xavier SP.Treatment of a commercial, machinedsurface titanium implant with H

2SO

4/

H2O

2 enhances contact osteogenesis. Clin.

Oral Implants Res. 18(4), 452–458 (2007).

86 Vetrone F, Variola F, Tambasco DeOliveira P et al. Nanoscale oxidativepatterning of metallic surfaces tomodulate cell activity and fate. Nano Lett. 9(2), 659–665 (2009).

87 Mendonca G, Mendonca DB, Aragao FJ,Cooper LF. Advancing dental implantsurface technology from micro tonanotopography. Biomaterials 29(28),3822–3835 (2008).

• Review of current developments on

nano- and micro-structures related mainly

to bone formation.

88 Jayaraman M, Meyer U, Buhner M, Joos U, Wiesmann HP. Influence oftitanium surfaces on attachment ofosteoblast-like cells in vitro. Biomaterials 25(4), 625–631 (2004).

89 Schneider GB, Zaharias R, Seabold D,Keller J, Stanford C. Differentiation ofpreosteoblasts is affected by implant surfamicrotopographies. J. Biomed. Mater.Res. A 69(3), 462–468 (2004).

90 Schwarz F, Ferrari D, Herten M et al. Effects of surface hydrophilicity andmicrotopography on early stages of soft anhard tissue integration at non-submergedtitanium implants: animmunohistochemical study in dogs. J. Periodontol . 78(11), 2171–2184 (2007)

91 Buser D, Broggini N, Wieland M et al. Enhanced bone apposition to a chemicallmodified SLA titanium surface. J. Dent.Res. 83(7), 529–533 (2004).

92 Zhao G, Schwartz Z, Wieland M et al. High surface energy enhances cell responto titanium substrate microstructure.

J. Biomed. Mater. Res. A 74(1), 49–58(2005).

93 Ellingsen JE, Johansson CB, Wennerberg A, Holmen A. Improved retention andbone-tolmplant contact with fluoride-modified titanium implants. Int. J. Oral Maxillofac. Implants 19(5), 659–666(2004).

94 Sun L, Berndt CC, Gross KA, Kucuk A.Material fundamentals and clinicalperformance of plasma-sprayedhydroxyapatite coatings: a review. J. Biome Mater. Res. 58(5), 570–592 (2001).

95 Faeda RS, Tavares HS, Sartori R,Guastaldi AC, Marcantonio E Jr. Biologiperformance of chemical hydroxyapatitecoating associated with implant surfacemodification by laser beam: biomechanicstudy in rabbit tibias. J. Oral Maxillofac.Surg. 67(8), 1706–1715 (2009).

96 Braceras I, De Maeztu MA, Alava JI,Gay-Escoda C. In vivo low-density boneapposition on different implant surfacematerials. Int. J. Oral Maxillofac. Surg. 38(3), 274–278 (2

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Superficies y oseointegración (1)