R E V I E W A R T I C L E
Biological reactions to diff erent dental implant surface
treatments
Mona Y. El-Gammal1, Nihal Y. El-Gammal2, Omar N. Fadhil3, Ola M. Maria4
1Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Mansoura University, Mansoura, Egypt, 2Department of Restorative Dentistry, Faculty of Dentistry, Ain shams University, Cairo, Egypt, 3Department of Prosthodontics, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia, 4Department of Oncology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
Abstract
The treatment of dental implants that increases surface area and roughness enhances bone-to-implant contact ratio; thus, facilitates the immediate loading of dental implants and fastens the osseointegration process. Structural and functional union of the implant with living bone is strongly infl uenced by the surface properties of the titanium (Ti) implants. As Ti and its alloys cannot directly bond with living bone, modifi cation of implant surface has been introduced to enhance osseointegration. The biological eff ect of diff erent methods of surface treatment has been studied in vivo and in vitro
experiments. This review outlines the biological aspects and the use of certain surface modifi cations to control bone-to-implant biological response. In this review, we tried to cover a large number of reported studies related to implant surface treatments. Many of these treatments have been tried in the clinic and showed satisfactory results; therefore, specifi c recommendation regarding the best biocompatible implant surface treatment was hard to conclude.
Keywords: Biological reaction, dental implant, laser sintered, osseointegration, surface treatment
Correspondence
Ola M. Maria, 1650 Cedar Avenue, Room L5-112, Montreal, Quebec, H3G 1A4, Canada. Tel.: +1 (44157) 514 934 1934. Fax: +1 514 934 8229.
E-mail: [email protected]
Received 20 October 2015; Accepted 21 March 2016
doi: 10.15713/ins.ijcdmr.97
How to cite the article:
Mona Y. El-Gammal, Nihal Y. El-Gammal, Omar N. Fadhil, Ola M. Maria, “Biological reactions to diff erent dental implant surface treatments,” Int J Contemp Dent Med Rev, vol. 2015, Article ID: 051015, 2015. doi: 10.15713/ins.ijcdmr.97
Introduction
Diff erent treatments of dental implants that increase surface area and roughness enhance bone-to-implant contact (BIC) ratio and facilitate the immediate loading of dental implants and fasten the osseointegration process. Immediately after surgical implantation, the implant becomes surrounded by necrotic bone and blood clot. A cascade of events takes place at the bone-implant interface begins with the interaction with water. Water molecules quickly bind to the implant surface, forming a mono or bilayer of water molecules.[1] The strength of water molecules
binding is directly related to the wettability of the implant surface. Water molecules bind to hydrophilic surfaces stronger than hydrophobic surfaces. Titanium (Ti) and hydroxyapatite (HA) are the materials of choice owing to their relatively high degree of hydrophilicity.[2] The quantity and quality of bone formed
around the implant are aff ected by the implant surface properties. The composition and charges of implant surface are determinants for protein adsorption and cell attachment.[3] Hydrophilicity is
aff ected by the surface chemical composition where hydrophilic surfaces are favorable for the interactions with biological fl uids and cells when compared to the hydrophobic ones.[4,5]
Various methods of implant surface treatment have been studied to improve the biological surface properties, which favor the mechanism of osseointegration,[6] with faster and stronger bone
formation, better stability is achieved during the healing process. Thus, more rapid loading of the implant is possible.[7] After the
water overlayer has formed, natural ions, such as chloride (Cl−) and sodium (Na+) enter the interface and become incorporated into the water overlayer. Moreover, proteins originating from blood and tissue fl uids at the wound site, reach the surface and initially adsorb, desorb (native or denatured) or are replaced by larger proteins at a later stage. Living cells appear on the stage when this dynamic layer of protein forms.[1] Certain proteins are
needed for cell anchorage, migration, and proliferation. Therefore, the composition of the adsorbed layer is a key mediator of cell behavior, determining which cells bind, how they bind and if they become activated. Hence, the required proteins, if correctly presented, can stimulate the formation of a newly organized tissue at the bone-implant interface.[2] The rapid adsorption of
Another objective can be achieved by implant surface modifi cations is to improve the clinical performance in areas with poor quantity/quality of bone, and stimulating bone growth in order to permit implant placement in sites that lack suffi cient residual alveolar ridge.[8] The amount of BIC is an
important determinant in the long-term success of dental implants. Maximizing the BIC, which is enhanced by implant surface roughness and osseointegration has become a goal of treatment.[9] In the metaphyses of the tibia and femur of
mini pigs, implants with 6 diff erent surface treatments were directly and morphometrically compared, after 3 and 6 weeks, with regard to BIC area.[4] Electro-polished and
medium-grit-blasted implant surfaces showed the lowest percentage of BIC area (20-25%). Large-grit-sandblasted and Ti plasma sprayed (TPS) implant surfaces had an average of 30-40% while large-grit-sandblasted and acid-etched implant surfaces had an average of 50-60% and HA-coated implant surfaces showed the highest BIC area (60-70%). The authors concluded that “the extent of bone-implant interface was positively correlated with an increased roughness of the implant surface.” In this review, we will discuss the diff erent biological reaction to certain dental implant surface treatments. Summary of advantages and disadvantages of diff erent types of implant surface treatment is provided in Table 1.
Biological Response to Implants
At the initial stages of bone healing, devitalized bone is removed by osteoclasts. Osteogenic cells deposit a non-collagenous matrix layer, similar to bone cement line and lamina limitans, onto the resorbed surface of the bone.[10] This calcifi ed afi brillar
layer, rich in calcium (Ca+2), phosphorus (P-), osteopontin and
bone sialoprotein, forms on any kind of biomaterial implanted, and arises the possibility for optimal “bonding” between the pre-existent bone and the implant, as it is involved in osteoblast attachment.[11] After few days, osteoblasts starts depositing
collagen matrix directly onto the early formed cement line, followed by the arrangement of the woven bone and developing bone trabeculae and marrow spaces. Therefore, it is thought that peri-implant osteogenesis starts from two directions: (i) Contact osteogenesis: From osteogenic cells, that were previously recruited to the implant surface and began secreting bone matrix, toward the pre-existing host bone, and (ii) distance osteogenesis: From the osteogenic cells, lining the remodeling borders of the pre-existent bone tissue, toward the implant surface.[12]
Implant Surface Roughness Techniques
Methods for roughening implant surface texture can be classifi ed into either additive or subtraction mechanisms. Additive mechanisms add particles on the biomaterial; create a surface with bumps, as in HA and other calcium phosphates (CaP) coatings, TPS and ion deposition implants. Subtraction mechanisms remove material from the implant surface; create pits or pores,
as in mechanical or electro-polishing, grit blasting, acid etching, oxidation and grit blasting followed by acid etching.[13]
Depending on the dimension of the measured surface features, implant surface roughness is divided into macro, micro, and nanoroughness. Macro roughness comprises features in the range of millimeters to tens of microns. This scale directly relates to the implant geometry, with a threaded screw and macroporous surface treatments. It improves the primary implant fi xation and long-term stability. Thus, increases the mechanical interlocking between the macrorough features of the implant surface and the surrounding bone.[14,15] Microroughness is in the range of
1-10 μm. It increases the interlocking between mineralized bone and implant surface. Some clinical evidences suggest that the micron-level surface topography results in the greater formation of bone at the implant surface.[16] Recently, surfaces provided
with nanoscale topographies are widely used. Nanotechnology includes materials that have nano-sized topography or are composed of nanosized materials with a range of 1-100 nm. Nanometer roughness plays a role in the adsorption of proteins, adhesion of osteoblasts and the rate of osseointegration.[17]
Implants surface roughness can be created by common mechanical, chemical or physical methods. Mechanical methods include grinding, blasting, machining, sandblasting large grit acid etching (SLA) and polishing treatments. Chemical methods depend on chemical reactions occurring at the interface between Ti and a solution including acids or alkali, hydrogen peroxide, sol-gel, chemical vapor deposition, and anodization. Chemical surface modifi cation of Ti alters its surface roughness, composition and may improve its wettability and surface energy.[18] Physical methods include plasma spraying, sputtering
and ion deposition. In the following paragraphs, we will focus on the biological responses related to the most commonly used methods of implant surface modifi cations.
Turned/machined (non-treated)
Studies on animal models and clinical studies have suggested a positive correlation between the implant surface roughness and BIC. The success rate of machined (non-treated) implants has been reported as less when placed in low bone density compared to good bone quality.[3,19] Osteoblasts are rugophilic; hence, they
tend to grow along the grooves existing on the implant surface. The disadvantage regarding the morphology of non-treated implants is that they provide mechanical resistance for bone interlocking.[20]
Ultrastructural studies demonstrated the presence of an amorphous unmineralized or partly mineralized zone that separates the Ti surface from the bone and lacks collagen
fi bers.[21] The rupture was reported to occur in the innermost
of this zone by unscrewing during removal torque testing. The stability of threaded machined Ti implants was therefore believed to be due to a mechanical interlock with surface irregularities at the microscopic level and/or geometrical deviations at the macroscopic level.[22] Sennerby et al. studied the
cortical bone after 3-180 days. They reported an early cellular response, a relative absence of infl ammatory cells and a rapid formation of woven bone from the endosteal surface. 7 days after implantation, solitary bone formation was observed in the threads and at the endosteal surface of the cortical bone. With time, both types of woven bone fused and increasingly fi lled the implant threads. The increased bone-Ti surface contact was thus a result of ingrowth of bone from the surroundings and did not start at the implant surface.[21]
Acid etched
Acid etched implant surface produces a micro texture rather than a macro texture. The dual acid etched (DAE) surfaces improve the osteoconductive process through the attachment of fi brin and osteogenic cells, enhancing bone formation directly on the implant surface.[23,24] When a higher temperature is used with an
acid etching method, they produce a homogeneous microporous surface with increased cell adhesion and greater BIC compared to TPS surfaces.[8]
The increased surface wettability was suggested to promote
fi brin adhesion, which provides contact guidance for the osteoblasts migrating along the implant surface.[4] In addition,
expression of platelet and extracellular genes promote the colonization of osteoblasts on implant surface and improves osseointegration. Experimental studies reported that DAE implants have shown greater BIC and less bone resorption compared to machined implants.[25,26]
Hydrophilic SLA alters human gingival fi broblast adhesion and the intracellular localization of extracellular signal-regulated kinase ½.[27]In vitro reports,[28-30] on cell response to
hydrophilic SLA, osteoblasts behavior was aff ected by altering protein absorption that directly induced diff erentiation by the assembly of focal adhesion sites (FAs) and intracellular
Table 1: Summery of advantages and disadvantages of diff erent types of implant surface treatments
Implant surface treatment Advantages Disadvantages
• Turned/machined • Bone interlocking • Macro rather than micro roughness
• Increased bone-Ti surface contact
• Bone ingrowth from surroundings and did not start at implant surface
• Acid etched • Homogeneous microporous surface with increased
cell adhesion and greater BIC compared to TPS surfaces
• Increased surface wettability promotes fi brin adhesion, which provides contact guidance for osteoblasts migration along implant surface
• Stochastic surface characteristics • Not 3D
• Laser sintering • Forms complex (3D) geometry
• Allows better osteoconductive process
• CaP coating • Precipitation of a biological apatite onto implant surface
• Early biological fi xation of implants
• Established positive bone-to-implant healing eff ect of CaP ceramic coatings
• Did not diff er in osteoporotic and non-osteoporotic healthy animal models
• HA coating • Bioactive
• Direct strong bone-to-implant bond
• Growth factors coating • Bio-adhesive motif, binds to adhesion receptors and promotes cell adhesion
• BMPs, can induce new bone formation
• BIC and osteoblast diff erentiation were not improved by RGD application
• Functionalization success depends on type, delivery and concentration of coating material
• Electrochemical anodization
• Ca+2 and P− enrichment of anodized surface helps to produce a chemical bond with the implant • Osteoconductive potential
• Fluoride treatment • Improved osteoblastic diff erentiation
• Sustained greater push-out forces and showed higher removal torque
• Decreased cell proliferation occurred aft er 7 days on F treated implants
• Biologically active drugs coating
• Bioactive
• Possibility to add an antibacterial eff ect
• Not commercially available
• TPS • Roughness of 7 μ can increase implant surface area • Similar pullout strength to HA implants
• Lower bone contact length on TPS surface compared to HA
• Alkali treatment • Bioactive • Not commercially available
signaling cascade activation.[28] The FAs are important sites
of signaling that control spreading, migration, cytoskeletal organization, cell cycle progression, gene expression and matrix
fi brillogenesis.[31-33]
Laser sintering
Previous studies showed that direct laser fabrication (DLF) implants have structures with complex geometry and could allow the better osteoconductive process. Evaluation of cytocompatibility and fi brin clot extension was carried out using osteoblasts and human blood to compare cell growth and fi brin clot covered areas on several implant surfaces. DLF implant surface showed lower cell density compared to machined, smooth textured grit blasted, and acid-etched implant surfaces. Inorganic acid etching slightly improved the extension of human blood to increase the micro roughness. Moreover, laser metal sintered implants were better adapted to the elastic properties of bone. Thereby, DFL implants could decrease stress-shielding eff ects and enhance implant long-term success rates.[34,35]
Laser-sintered Ti implants showed high purity with enough roughness for good osseointegration compared to other treatments.[36] Biological evaluation of the role of Ti ablation
and chemical properties showed the ability of its grooved surface to orientate osteoblasts attachment and control the direction of ingrowth.[37] We designed a clinical study to evaluate
laser-sintered one-piece implants (OPI) placed in the mandibular premolar area and subjected to early loading after 3 weeks of initial placement. In this study, we reported satisfactory results based on clinical and radiographic evaluation for 1 year of follow-up and stated that laser-sintered early-loaded OPI is a good alternative to the two-piece machined implants.[38]
CaP coating
Coating of dental Ti implants with CaP ceramic is commonly used to change the chemical composition of the implant surface.[12] After implant placement, the CaP particles are released
into the peri-implant region; raising the saturation of body fl uids and leading to the precipitation of a biological apatite onto the implant surface.[39,40] Endogenous proteins present in this layer
of biological apatite act as a matrix for osteogenic cell attachment and growth.[11] Integrins mediate the cellular interactions with
the apatite layer and its proteins onto the implant surface. The signaling pathways via integrins can regulate bone forming cell activity.[38,39] The bone stimulating action of CaP coatings at
implant surface enhances early osseointegration compared to non-CaP coated dental implants.[41] The biological fi xation of
Ti implants coated with CaP to bone tissue takes place earlier compared to non-CaP coated implants.[42] Therefore, CaP
ceramic-coated implants have been suggested for osteoporotic bone to compensate for low bone quantity/density and for impaired or delayed bone regeneration.[43-46] The established
positive bone-to-implant healing eff ect of CaP ceramic coatings did not diff er in osteoporotic and non-osteoporotic healthy animal models.[47]
HA coating
Several methods have been used for applying HA coatings onto metals, and each method can result in diff erent material properties. Plasma spraying that forms a coating thickness of 40-50 μm is the most common used technique for coating Ti implants. A synthetic form of HA has a similar chemical composition to the mineral matrix of bone.[48] HA can form
a direct and strong bone-to-implant bond. After implant placement, HA acts as a bioactive material where a sequence of events results in precipitation of a CaP rich layer on the implant surface through a solid solution ion exchange at the implant-bone interface. The CaP incorporated layer will be developed in a biologically equivalent HA that will be incorporated in the developing bone through octacalcium phosphate.[49]
The inorganic phase in bone tissue is mainly composed of carbonate-rich HA. HA ceramics has been an obvious candidate for deposition as a coating onto bone implant surfaces. These HA coatings were proved to be bioactive and stimulate the formation of new bone tissue. In many preclinical and clinical studies calcium-to-phosphate ratio, phase composition and crystal structure, are used as chemical parameters, to optimize the performance of CaP coatings.[50] HA coatings showed a
persistent signifi cant improvement of the osteoconductivity of metallic implants.[51-53] During the past two decades, recent trends
in research on CaP coatings mainly focused on modifi cation of its chemical structure and addition of ionic dopants. Recently, several types of CaP-based coatings have been explored such as pure HA, Silicon-containing HA,[54] strontium-doped HA,[55]
magnesium-substituted HA,[56] bisphosphonate and HA,[57]
carbonated HA,[58]fl uorinated HA,[59] and antibacterial
silver-containing HA.[60]
Growth factors coating
Implant surfaces can be coated with biomolecules, such as; bio-adhesive motifs or growth factors, to promote osseointegration. The RGD sequence from fi bronectin is the most common used bio-adhesive motif that binds to adhesion receptors and promotes cell adhesion.[61] RGD functionalized and
tissue-engineered constructs can improve early bone ingrowth and matrix mineralization in vivo.[62,63]
Nowadays, numerous materials have been RGD functionalized for medical applications. However, BIC and osteoblast diff erentiation were not improved by RGD application to Ti implant surfaces.[64,65] This might be due to the absence of
crucial modulatory domains from the native fi bronectin; the RGD signals disappear by non-specifi c adsorption of plasma protein and interactions with infl ammatory components.[66] On
the other hand, Germanier et al. compared sandblasted implant surfaces that were either RGD peptide polymer coated or uncoated and placed in the maxillae of minipigs. They concluded that RGD coating might enhance bone apposition at the early stages of bone regeneration.[67]
eff ect in extraskeletal sites; BMPs induce the diff erentiation of cells derived from soft tissues into bone forming cells.[69] BMP-2
can promote re-osseointegration of peri-implant defects. In non-human primates, peri-implant defect made over 11 months in HA coated implant, and BMP-2 was placed using collagen sponge carrier. Histomorphometric analysis after 16 months showed that the vertical bone healing in BMP-2 treated implants is equal to three folds that of the untreated.[70] Liu et al.
compared the eff ects of BMP-2 and its mode of delivery on the osteoconductivity of dental implants with either a machined or a CaP-coated Ti surface in the maxillae of minipigs. The bone volume formed after 3 weeks within the osteoconductive space (peri-implant) was highest for CaP-coated and uncoated implants with no BMP-2, while was the lowest for adsorbed BMP-2 CaP-coated implants. Hence, the osteoconductivity of functionalized implant surfaces was aff ected by the method of BMP-2 delivery, being impaired when BMP-2 is present as a superfi cially adsorbed depot on CaP-coated or uncoated surfaces.[71] Wikesjo et al. studied osseointegration and vertical
bone formation by recombinant human BMP-2 (rhBMP-2) coated onto a Ti porous oxide implant surface. A critical size, 5 mm, supra-alveolar peri-implant defects were created and implants coated with rhBMP-2 at 0.75 or 1.5 or 3.0 mg/mL or uncoated controls were installed and compared. New bone was formed with characteristics of the adjoining resident Type II bone including cortex formation at rhBMP-2 coated implant sites with the concentration of 0.75 or 1.5 mg/mL. However, sites coated with rhBMP-2 at 3.0 mg/mL concentration showed more immature trabecular bone formation and peri-implant bone remodeling that resulted in implant displacement.[72] The
rhBMP-2 coated Ti porous oxide implants induced clinically more local bone formation in vertical ridge augmentation and osseointegration, but higher rhBMP-2 concentrations were accompanied with negative eff ects.[73] Therefore, the
success of functionalization depends on the type, delivery and concentration of the coating material.
Platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) were used in combination around implants where they can produce 2-3 times more new bone within 7 days compared to controls. However, after 21 days, in spite of a large volume of new bone formed around dental implants treated with growth factors, there was no signifi cant diff erence between growth factor and control sites. Thus, the use of PDGF/IGF may only accelerate the process of bone formation.[74]
Electrochemical anodization
The electrochemical anodization can produce a mixed nano/submicron scale Ti oxide (TiO2) network layer (lateral pore size: 20-160 nm) on a polished Ti surface in 10 min. This TiO2 network layer improved the whole blood coagulation and human bone marrow stem cell adhesion on a Ti dental implant surface.[75] The galvanic anodization of Ti in strong acids
produces a thick layer of TiO2. Some researchers think that Ca +2
and P- enrichment of the anodized surface helps to produce a
chemical bond between the implant and the peri-implant bone, leading to a higher bone-to-implant interfacial shear strength.[76,77]
Burgos et al. compared implant surface manufactured by anodic oxidation to turned surfaces in a rabbit model. BIC values were 20%, 23%, and 46% around the oxidized surfaces with a diff erent osseointegration pattern, while 15%, 11%, and 26% around the machined surfaces, after 7, 14 and 28 days, respectively.[78]
Huang et al. studied the oxidized implant surfaces placed in the posterior maxilla of monkeys. After 16 weeks, the recorded mean of BIC was 74%. They stated that this oxidized surface showed a considerable osteoconductive potential resulting in a high level of implant osseointegration in Type IV bone.[79]
Fluoride treatment
Ti can react to fl uoride (F) ions, forming soluble TiF4 that enhances osseointegration of dental implants. The analysis of human mesenchymal cells showed no diff erence in cell attachment between the F treated and control (grit-blasted) implants. However, decreased cell proliferation occurred after 7 days on F treated implants compared to controls. This chemical surface treatment improved osteoblastic diff erentiation in comparison to control implants. Fluoridated implants also sustained greater push-out forces and showed higher removal torque than control implants.[80] In addition, it increased
osteoblast diff erentiation represented by increased expression of Cbfa1, osterix, and bone sialoprotein.[81]
Biologically active drugs coating
Bisphosphonate coated Ti implants improved local bone density in the peri-implant region,[82] due to its anti-resorptive
eff ect limited to the implant site. Du et al. studied the eff ect of simvastatin, by oral administration, on implant osseointegration in osteoporotic rats and showed that it can enhance implant osseointegration.[83] Intraperitoneal administration of
simvastatin increased BIC ratio and bone density and might have the potential to enhance osseointegration.[84] Yang et al. reported
that simvastatin loaded porous implant surfaces accelerated osteogenic diff erentiation of preosteoblasts, which can enhance the process of osseointegration.[85]
Coating implants with antibacterial substances provides an antibacterial property to the implant itself. Tetracycline-HCl has the ability to kill microorganisms that may contaminate the implant surface and can remove the smear layer and endotoxins from the implant surface. In addition, it prevented the action of collagenase, increased cell proliferation, attachment, and bone healing, improved blood clot attachment and retention on the implant surface during the early phase of healing, thus enhanced osseointegration.[86]
TPS
increases the implant surface area. Al-Nawas et al. compared diff erent types of macro and micro structure implant surfaces in dogs. After 8 weeks of healing and 3 months of loading, higher BIC values of TPS rough surfaces and blasted/acid-etched implants were reported in comparison to machined ones. The diff erence between the TPS and the blasted/acid-etched implants BIC values was not signifi cant.[87] In rabbits, Klokkevold et al. evaluated the torque resistance to removing screw shaped Ti implants that were with either DAE or machined, or TPS surface; TPS surface exhibited a signifi cantly more complex surface topography.[88] An in vivo study that evaluated TPS versus
plasma sprayed HA implants, showed that bone contact length for HA implants was signifi cantly higher than TPS at 12 weeks of implant placement and 1 year of loading. TPS implants showed similar pull out strength compared to the HA implants. The lower bone contact length on TPS surface compared to HA surfaces had no eff ect on the bone-to-implant strength in both implant types.[89]
Alkali treatment
NaOH treatment includes the formation of a bioactive sodium titanate layer on orthopedic Ti surfaces. Following the immersion in stimulated body fl uids (SBF), bone-like apatite is deposited onto this layer.[90] Sodium ions in the titanate layer
are exchanged with H3O+ ions from the SBF forming Ti-OH groups, which combine with Ca+2 ions to produce amorphous
calcium titanate. The reaction with phosphate polyatomic ions forms amorphous CaP, which transforms into bone-like apatite.[91] Alkali treatment and biomimetic precipitation of CaP
coatings are techniques that can be used to coat the interior of porous metallic surfaces.[92-94]
Conclusions
In addition to surface roughness treatments, surface chemistry manipulation of the porous implant surface, further enhances osseointegration and strengthens BIC. Biological bone reactions to most implant surface treatments were satisfactory. Studies on the development of osteogenic implant surface favor immediate or early loading of dental implants. In this review, we tried to cover a large number of reported studies related to implant surface treatments. However, it is hard to identify the best type of surface treatment based on the biocompatibility of treated implant surface.
Acknowledgments
The authors would like to thank Mansoura University for funding.
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