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Surface modification of dental biomaterials for controlling bone response
Abstract
The bone healing process at the interface between the bone and the implant surface consists of hemostasis, inflammation, proliferation, and remodeling. The implant surface modification can help to quickly switch from inflammation to proliferation. Clinically, this means fast osseointegration and patient's reduced edentulous period. Furthermore, via such a method to modify the surface, the implant-supported restoration is able to serve a patient having the systemic condition that made the implant treatment contraindicated in the past. Commercially pure titanium surface is modified to a roughened surface showing the accelerated bone response. Subsequently, some chemical features are added to the roughened surface, such as hydrophilicity, calcium phosphorus effects, and fluoride characteristics. Recently, researchers are developing biological surfaces for faster and stronger osseointegration, using cell adhesion molecules and growth factors.
... 39 Bleeding and damaged endothelium from injured blood vessels form platelet plugs, simultaneously provoking the coagulation cascade toward hemostasis. 40,41 The surface of an implant initially contacts blood during the implant insertion into the hole. Surface wettability, charge, and topography play an important role in initial bone healing. ...
... 48 These macrophages stimulate fibrogenesis by fibroblasts, an essential component in wound healing (Fig. 1C). 41,44,49 Various cytokines released from the macrophages contribute to wound healing, as does the primary stability of the implants. 40,44 The loss of primary stability, or micromovement, of the implant produces shear stress that disrupts normal bone healing. ...
... Bone resorption by osteoclasts is balanced with bone formation by osteoblasts. 40,41 The osteogenic cells lining the cement line dissolve the osteoid with collagenases, thereby exposing RGD (tripeptide arginine, glycine, and aspartate) endings from the surface and causing cell detachment. 40,53 Migrating osteoclast precursors are attracted by the recently exposed bone surface and become attached. ...
Surface characteristics are an important factor for long-term clinical success of dental implants. Alterations of implant surface characteristics accelerate or improve osseointegration by interacting with the physiology of bone healing. Dental implant surfaces have been traditionally modified at the microlevel. Recently, researchers have actively investigated nano-modifications in dental implants. This review explores implant surface modifications that enhance biological response at the interface between a bone and the implant.
... The Ti surface of a dental implant is originally hydrophobic [14]. Water (H 2 O) is considered to have initial contact with the implant surface when the implant is inserted into the bone [15]. Therefore, there have been attempts to add hydrophilicity to an SLA surface, since hydrophilicity is expected to help accelerate the bone healing process [14,16]. ...
... Therefore, there have been several techniques developed to thicken and stabilize the Ti oxide layer, which is considered to increase the biocompatibility of the surface [25][26][27]. When Ti becomes the anode under an electric potential in an electrochemical cell, Ti is oxidized to be Ti 4+ , and the TiO 2 layer is able to be thickened and roughened [15]. Topographically, the oxidized Ti surface for a dental implant has many volcano-like micropores with various sizes, which are observed in SEM. ...
... Topographically, the oxidized Ti surface for a dental implant has many volcano-like micropores with various sizes, which are observed in SEM. The surface characteristics of the anodized Ti surface depend on the applied potential, surface treatment time, concentrations, and types of electrolytes [15,27]. The arithmetic mean height of this surface, or Sa, is evaluated to be approximately 1 to 1.5 µm for dental use [28][29][30][31]. ...
This review paper describes several recent modification methods for biocompatible titanium dental implant surfaces. The micro-roughened surfaces reviewed in the literature are sandblasted, large-grit, acid-etched, and anodically oxidized. These globally-used surfaces have been clinically investigated, showing survival rates higher than 95%. In the past, dental clinicians believed that eukaryotic cells for osteogenesis did not recognize the changes of the nanostructures of dental implant surfaces. However, research findings have recently shown that osteogenic cells respond to chemical and morphological changes at a nanoscale on the surfaces, including titanium dioxide nanotube arrangements, functional peptide coatings, fluoride treatments, calcium–phosphorus applications, and ultraviolet photofunctionalization. Some of the nano-level modifications have not yet been clinically evaluated. However, these modified dental implant surfaces at the nanoscale have shown excellent in vitro and in vivo results, and thus promising potential future clinical use.
... Dental implants made of titanium, especially commercially pure titanium, have become a wellestablished treatment modality for the replacement of missing teeth and are state of the art in the field of dental restoration [1]. The concept of osseointergration was introduced by Branemark in the mid 1960's [2]. ...
... In order to improve the speed and strength of bone formation and to allow more rapid loading of the implants, researchers have investigated the effects of modifying implant surfaces. The surface modification is considered to start from the topographical change of the surface or increasing the roughness of the titanium surface [1]. Surface roughness has an important role in enhancing bone healing and promoting biomechanical properties at the bone/implant interface through increasing the mechanical retention and allowing good stress distribution [4]. ...
The biocompatibility of dental implants is dependent on good interaction between implant-human body tissue and a good osseointegration. The surface roughness plays an important role enhancing bone healing and promoting biomechanical properties at the bone/implant interface. The increase in surface roughness can simultaneously improve cell migration and attachment of an implant, and enhance the osseointegration process. However surface roughness has shown to be detrimental to corrosion, raising the need to achieve a balance between good osseointegration and corrosion performance. This study characterised the corrosion performance of commercially pure titanium grade 4 with different surface conditionings. Implants in the form of 15 mm discs and implant screws were tested in basic Ringers lactate solution of pH 5.5 at 37°C and in modified Ringers of pH 2. Corrosion tests included open circuit potential (OCP), potentiodynamic polarization test (PDP) and mass loss corrosion tests. Metallurgical characterisation showed that titanium Grade 4 consisted of equiaxed alpha (α-Ti) grains. The OCP test showed that the machined implants were nobler than the roughened implants. The corrosion rates obtained were very low, below 0.13 mm/y which is an acceptable corrosion rate for biomaterial design and application. Mass-loss tests showed that the alloys passivated regardless of the surface conditioning. The machined surface had a corrosion resistance higher than that of the roughened surface finish in all conditions.
... Therefore, several techniques have been reported regarding implant surface modification at submicron (1-10 micron)-level topographical modification and the addition of nanotechnological chemical features to the implant surface [165]. The fundamental coating principle of commercially pure titanium (cp-Ti) implant modification was intended to improve the early biological response (growth factors release from the bone matrix) to dental implants that commenced at the surgical osteotomy sites [166]. Additionally, the longstanding clinical survival of dental implants demands that the bone remodeling process should be harmonized with the modified implant surface to achieve predictable success. ...
Dental implants are frequently used to support fixed or removable dental prostheses to replace missing teeth. The clinical success of titanium dental implants is owed to the exceptional biocompatibility and osseointegration with the bone. Therefore, the enhanced therapeutic effectiveness of dental implants had always been preferred. Several concepts for implant coating and local drug delivery had been developed during the last decades. A drug is generally released by diffusion-controlled, solvent-controlled, and chemical controlled methods. Although a range of surface modifications and coatings (antimicrobial, bioactive, therapeutic drugs) have been explored for dental implants, it is still a long way from designing sophisticated therapeutic implant surfaces to achieve the specific needs of dental patients. The present article reviews various interdisciplinary aspects of surface coatings on dental implants from the perspectives of biomaterials, coatings, drug release, and related therapeutic effects. Additionally, the various types of implant coatings, localized drug release from coatings, and how released agents influence the bone-implant surface interface characteristics are discussed. This paper also highlights several strategies for local drug delivery and their limitations in dental implant coatings as some of these concepts are yet to be applied in clinical settings due to the specific requirements of individual patients.
... Vitronectin, one of the ECM proteins, is an abundant multifunctional glycoprotein found in serum, the extracellular matrix, and bone, and is involved in various physiological processes such as cell attachment, spreading, and migration [6][7][8]. Vitronectin contributes to healing of the bone surrounding a dental implant by promoting the attachment and spreading of the osteogenic cells [9,10]. was synthesized using the 9-fluorenylmethoxycarbonyl-based solid-phase method with a C-terminal amide using a Pioneer Peptide Synthesizer (Applied Biosystems, Foster City, CA, USA) in the Peptron (Daejeon, Korea). ...
In this study, we evaluated early bone responses to a vitronectin-derived, minimal core bioactive peptide, RVYFFKGKQYWE motif (VnP-16), both in vitro and in vivo, when the peptide was treated on sandblasted, large-grit, acid-etched (SLA) titanium surfaces. Four surface types of titanium discs and of titanium screw-shaped implants were prepared: control, SLA, scrambled peptide-treated, and VnP-16-treated surfaces. Cellular responses, such as attachment, spreading, migration, and viability of human osteoblast-like HOS and MG63 cells were evaluated in vitro on the titanium discs. Using the rabbit tibia model with the split plot design, the implants were inserted into the tibiae of four New Zealand white rabbits. After two weeks of implant insertion, the rabbits were sacrificed, the undecalcified specimens were prepared for light microscopy, and the histomorphometric data were measured. Analysis of variance tests were used for the quantitative evaluations in this study. VnP-16 was non-cytotoxic and promoted attachment and spreading of the human osteoblast-like cells. The VnP-16-treated SLA implants showed no antigenic activities at the interfaces between the bones and the implants and indicated excellent bone-to-implant contact ratios, the means of which were significantly higher than those in the SP-treated implants. VnP-16 reinforces the osteogenic potential of the SLA titanium dental implant.
... Surface roughness is typically reported using only the arithmetical mean height of the surface, Sa (some examples: [19,50,51]). It is often argued that Sa of 1-2 μm in titanium implants is optimal for bone integration [52]. ...
Bioinert zirconia and alumina ceramic devices are widely used, both in orthopaedics and in dentistry. In order to improve their bonding with bone tissues or dental resin cements, their surfaces are often roughened at different scales. In this work, we have investigated the effects of the same sandblasting treatment on alumina, zirconia and a zirconia-toughened alumina, focusing on their mechanical performance and the interplay between surface defects and residual stresses. Additionally, we explored the impact of the treatment on the hydrothermal aging of the two zirconia-containing materials. Residual stresses generated during sandblasting were always predominant over surface defects but their effect varied with the material: while they had a weakening effect on alumina, they reinforced both zirconia-containing materials. Finally, we found that the monoclinic grains at the surface of sandblasted zirconia recrystallized into tetragonal nanograins after annealing and this led to an increased resistance to aging.
Anatomically, the human tooth has structures both embedded within and forming part of the exterior surface of the human body. When a tooth is lost, it is often replaced by a dental implant, to facilitate the chewing of food and for esthetic purposes. For successful substitution of the lost tooth, hard tissue should be integrated into the implant surface. The microtopography and chemistry of the implant surface have been explored with the aim of enhancing osseointegration. Additionally, clinical implant success is dependent on ensuring that a barrier, comprising strong gingival attachment to an abutment, does not allow the infiltration of oral bacteria into the bone-integrated surface. Epithelial and connective tissue cells respond to the abutment surface, depending on its surface characteristics and the materials from which it is made. In particular, the biomechanics of the implant-abutment connection structure (i.e., the biomechanics of the interface between implant and abutment surfaces, and the screw mechanics of the implant-abutment assembly) are critical for both the soft tissue seal and hard tissue integration. Herein, we discuss the clinical importance of these three interfaces: bone-implant, gingiva-abutment, and implant-abutment.
Recent studies have shown that direct laser metal sintering (DLMS) produces structures with complex geometry and consequently that allow better osteoconductive properties. The aim of this patient report was to evaluate the early bone response to DLMS implant surface retrieved from human jaws. Four experimental DLMS implants were inserted in the posterior mandible of four patients during conventional dental implant surgery. After 8 weeks, the micro-implants and the surrounding tissue were removed and prepared for scanning electron microscopy (SEM) and histomorphometric analysis to evaluate the bone-implant interface. The SEM and EDX evaluations showed a newly formed tissue composed of calcium and phosphorus. The bone-to-implant contact presented a mean of 60.5 ± 11.6%. Within the limits of this patient report, data suggest that the DLMS surfaces presented a close contact with the human bone after a healing period of 8 weeks.
Recent clinical studies indicate that an implant with a textured surface may be loaded sooner than traditional healing protocols have recommended. In a previous study, the 6-month bone-implant contact for dual acid-etched and machined implant surfaces was reported to be 72.96% and 33.98%, respectively. In 1991, a minimum of 50% bone-implant contact was considered necessary for loading to ensure long-term survival of the implant. This study evaluated the 2-month bone-implant contact for dual acid-etched and machined implant surfaces to determine if this criterion had been met.
Custom manufactured implants (2 mm diameter and 5 mm length), having on one side a machined surface and on the other side a dual acid-etched surface, were placed in the posterior maxilla of 11 patients, allowed to integrate for 2 months, then removed using a 4 mm internal diameter trephine with irrigation. Sections were processed and stained for histologic and histomorphometric analysis. The parameters calculated for each section were: bone volume (BV%), actual percent bone-implant contact (BIC%), and expected bone contact (EBC%) as determined from 3 implant images superimposed onto the adjacent bone 150, 500, and 1,000 microm lateral to the actual implant surface and representing the bone-implant contact expected on the day the implant was placed, based on the peri-implant bone volume.
Histomorphometric analysis indicated that the mean BV% of 36.77% from all sections was closely matched to the mean EBC% of 34.36% (P<0.001). The analysis showed that after 2 months of healing, the 47.81% BIC% on the dual acid-etched side was statistically higher (analysis of variance, P<0.001) than the 19.00% BIC% on the machined side. In areas of low-density bone (<40% BV%), the difference between the BIC% for the machined and dual acid-etched sides was even greater. Nine of the 11 dual acid-etched sides had a higher BIC% than the EBC% value. In the machined group, 1 of the 11 sides had a higher BIC% value than the EBC% value. The bone surrounding the dual acid-etched surface was a woven bone with thin, connecting peri-implant bony trabeculae projecting into and between the threads. Bone on the machined side was observed mostly contacting the tips of the screw threads.
At 2 months, the mean BIC% for the dual acid-etched group increased 39.14% compared to the EBC% value, while the mean BIC% for the machined group decreased 44.70%. Based on the histomorphometric results of this study, sufficient bone for functional loading of the implant exists on a dual acid-etched surface after 2 months of healing in the posterior maxillary arch.
Microrough titanium (Ti) surfaces of dental implants have demonstrated more rapid and greater bone apposition when compared with machined Ti surfaces. However, further enhancement of osteoblastic activity and bone apposition by bio-functionalizing the implant surface with a monomolecular adsorbed layer of a co-polymer - i.e., poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its derivatives (PLL-g-PEG/PEG-peptide) - has never been investigated. The aim of the present study was to examine early bone apposition to a modified sandblasted and acid-etched (SLA) surface coated with an Arg-Gly-Asp (RGD)-peptide-modified polymer (PLL-g-PEG/PEG-RGD) in the maxillae of miniature pigs, and to compare it with the standard SLA surface. Test and control implants had the same microrough topography (SLA), but differed in their surface chemistry (polymer coatings). The following surfaces were examined histomorphometrically: (i) control - SLA without coating; (ii) (PLL-g-PEG); (iii) (PLL-g-PEG/PEG-RDG) (RDG, Arg-Asp-Gly); and (iv) (PLL-g-PEG/PEG-RGD). At 2 weeks, RGD-coated implants demonstrated significantly higher percentages of bone-to-implant contact as compared with controls (61.68% vs. 43.62%; P < 0.001). It can be concluded that the (PLL-g-PEG/PEG-RGD) coatings may promote enhanced bone apposition during the early stages of bone regeneration.
In a study model that aims to evaluate the effect of nanotopography on bone formation, micrometer structures known to alter bone formation, should be removed. Electropolished titanium implants were prepared to obtain a surface topography in the absence of micro structures, thereafter the implants were divided in two groups. The test group was modified with nanosize hydroxyapatite particles; the other group was left uncoated and served as control for the experiment. Topographical evaluation demonstrated increased nanoroughness parameters for the nano-HA implant and higher surface porosity compared to the control implant. The detected features had increased size and diameter equivalent to the nano-HA crystals present in the solution and the relative frequency of the feature size and diameter was very similar. Furthermore, feature density per microm(2) showed a decrease of 13.5% on the nano-HA implant. Chemical characterization revealed calcium and phosphorous ions on the modified implants, whereas the control implants consisted of pure titanium oxide. Histological evaluation demonstrated significantly increased bone formation to the coated (p < 0.05) compared to uncoated implants after 4 weeks of healing. These findings indicate for the first time that early bone formation is dependent on the nanosize hydroxyapatite features, but we are unaware if we see an isolated effect of the chemistry or of the nanotopography or a combination of both.
OBJECTIVES:
It was the aim of this study to analyze osseointegrative properties of porous additive manufactured titanium implants made by direct metal laser sintering in a sheep model after an implantation period of 2 and 8 weeks.
MATERIAL AND METHODS:
Three different types of implants were placed in the pelvis of six sheep. In each sheep were placed three standard machined (M), three sandblasted and etched (SE), and three porous additive manufactured (AM) implants. Of these three implants (one per type) were examined histologically and six implants were tested biomechanically. Additionally a semiquantitative histomorphometrical and qualitative fluorescent microscopic analysis were performed.
RESULTS:
After 2 and 8 weeks bone-to-implant-contact (BIC) values of the AM surface (2w: 20.49% ± 5.18%; 8w: 43.91% ± 9.69%) revealed no statistical significant differences in comparison to the M (2w: 20.33% ± 11.50%; 8w: 25.33% ± 4.61%) and SE (2w: 43.67 ± 12.22%; 8w: 53.33 ± 8.96%) surfaces. AM surface showed the highest increase of the BIC between the two observation time points. Considering the same implantation period histomorphometry and fluorescent labelling disclosed no significant differences in the bone surrounding the three implants groups. In contrast Removal-torque-test showed a significant improve in fixation strength (P ≤ 0.001) for the AM (1891.82 ± 308, 44 Nmm) surface after eight weeks in comparison to the M (198.93±88,04 Nmm) and SE (730.08 ± 151,89 Nmm) surfaces.
CONCLUSION:
All three surfaces (M, SE, and AM) showed sound osseointegration. AM implants may offer a possible treatment option in clinics for patients with compromised bone situations.
Objective
The aim of this study was to estimate the effects of zirconia implants and recombinant human bone morphogenetic protein-2 (rhBMP-2) gel on the acceleration of local bone formation and osseointegration in the canine mandible. Materials and Methods
Four groups of 48 implants with identical geometry were installed in the mandibles of beagle dogs: alumina-blasted zirconia implants applied with rhBMP-2, alumina-blasted zirconia implants applied with demineralized bone matrix (DBM), alumina-blasted zirconia implants, and resorbable blast media-treated titanium (Ti) implants. For the first two groups, zirconia implants were inserted after the surgical sites were filled with rhBMP-2 or DBM gel. For the other two groups, zirconia or Ti implants were installed with no adjunctive treatment. Fluorescent bone markers were administered to monitor bone remodeling at weeks 2, 4, and 5 postimplantation. After healing periods of 3weeks and 6weeks, the animals were sacrificed, and fluorescent microscopy, histology, and histomorphometric analyses were performed. ResultsFluorescent microscopy showed that bone formation around the zirconia implants installed with rhBMP-2 gel was the most prominent at 2weeks postimplantation, while the Ti implants acquired bone apposition mainly at week 5. No significant differences were found in bone area among the groups (P>0.05). The zirconia implants showed similar bone-to-implant contact to the Ti implants. There were no significant differences in bone-to-implant contact between the zirconia implants with rhBMP-2 gel and those with DBM (P>0.05). Conclusions
The zirconia implants with alumina-blasted surfaces may achieve osseointegration in much the same manner as the well-established Ti implants. The area influenced by rhBMP-2 gel, including the alveolar crest, may cause active remodeling and early bone formation.
Bone formation and maintenance around implants placed immediately after tooth extraction may be affected by implant surface treatment and compromise long-term esthetic results. This study morphometrically evaluated buccal bone loss and bone-to-implant contact (BIC) of four implant systems placed immediately after tooth extraction in a dog model.
The premolars of eight beagle dogs were bilaterally extracted with a full-thickness flap, and root-form dental implants were placed on the root extraction socket. Implants (n = 16 each) with different surface treatments were placed from sites 1 to 4 and alternated between animals to allow evaluation of the same number of implants at sites and evaluation time points. Implant surface treatments were as follows: anodized, discrete crystalline deposition, SLActive, and microblasted. The left and right side provided implants that stayed for 2 and 4 weeks, respectively. Submerged healing was allowed and bone-to-implant contact (BIC) and buccal bone loss were morphometrically measured. Linear mixed models (P < 0.05) were used to assess differences between groups, across time, and their interaction.
Buccal bone loss was observed to approximately double between 2 and 4 weeks (P = 0.01). BIC also increased between 2 and 4 weeks, by 20–25% (P = 0.01). These changes were statistically similar for each surface.
When placed immediately after tooth extraction, the evaluated histomorphometric parameters vary only with time.
Objective:
It is unclear whether surface bioactive chemistry or hydrophilicity plays a more dominant role in the osseointegration of micro-structured titanium implants having the same surface topography at the micrometer and submicrometer scales. To understand their comparative effect on enhancing the early osseointegration of micro-rough-surfaced implants, this study compared the bone healing-promoting effect of surface strontium (Sr) chemistry that has been shown in numerous studies to super-hydrophilicity in the early osseointegration of moderately rough-surfaced clinical oral implants (SLA(®) implant) in rabbit cancellous bone.
Material and methods:
Hydrothermal treatment was performed to incorporate Sr ions into the surface of clinical SLA implants (SLA/Sr implant). The surface characteristics were evaluated by using field emission-scanning electron microscopy, X-ray photoelectron spectroscopy and optical profilometry. Twenty screw implants (10 control and 10 experimental) were placed in the femoral condyles of 10 New Zealand White rabbits. The early osseointegration of the SLA/Sr implant was compared with a chemically modified super-hydrophilic SLA implant (SLActive(®) implant) by histomorphometric and resonance frequency analysis after 2 weeks of implantation.
Results:
The SLA/Sr and SLActive implants exhibited an identical surface topography and average R(a) values at the micron and submicron scales. The SLA/Sr implant displayed a high amount of surface Sr content (15.6 at.%). There was no significant difference in the implant stability quotient (ISQ) values between the two groups. However, histomorphometric analysis revealed a significantly higher bone-to-implant contact percentage in the SLA/Sr implants compared with the SLActive implants in rabbit cancellous bone (P < 0.01).
Conclusion:
The results indicate that the surface Sr chemistry surpasses the effect of super-hydrophilicity in promoting the early bone apposition of moderately rough Ti surface in cancellous bone.
Roughened implant surfaces are thought to enhance osseointegration. Torque removal forces have been used as a biomechanical measure of anchorage or osseointegration in which the greater forces required to remove implants may be interpreted as an increase in the strength of osseointegration. The purpose of this study was to compare the torque resistance to removal of screw shaped titanium implants having an acid etched (HC1/H2SO4) surface (Osseotite) with implants having a machined surface. Two custom screw shaped implants, 1 acid etched and the other machined, were placed into the distal femurs of 10 adult New Zealand White rabbits. These implants were 3.25 mm in diameter x 4.00 mm in length without holes, grooves or slots to resist rotation. Following a 2 month healing period, the implants were removed under reverse torque rotation with a digital torque measuring device. Two implants with the machined surface preparation failed to achieve osseointegration. All other implants were found to be anchored to bone. Resistance to torque removal was found to be 4 x greater for the implants with the acid etched surface as compared to the implants with the machined surface. The mean torque values were 20.50 +/- 6.59 N cm and 4.95 +/- 1.61 N cm for the acid etched and machined surfaces respectively. The results of this study suggest that chemical etching of the titanium implant surface significantly increases the strength of osseointegration as determined by resistance to reverse torque rotation.
TiO(2) is one of the most studied compounds in materials science. Owing to some outstanding properties it is used for instance in photocatalysis, dye-sensitized solar cells, and biomedical devices. In 1999, first reports showed the feasibility to grow highly ordered arrays of TiO(2) nanotubes by a simple but optimized electrochemical anodization of a titanium metal sheet. This finding stimulated intense research activities that focused on growth, modification, properties, and applications of these one-dimensional nanostructures. This review attempts to cover all these aspects, including underlying principles and key functional features of TiO(2), in a comprehensive way and also indicates potential future directions of the field.
Studies using ectopic rodent, orthotopic canine, and non-human primate models show that bone morphogenetic proteins (BMPs) coated onto titanium surfaces induce local bone formation. The objective of this study was to examine the ability of recombinant human BMP-2 (rhBMP-2) coated onto a titanium porous oxide implant surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge.
Bilateral, critical-size, 5 mm, supra-alveolar, peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml, and six animals received implants coated with rhBMP-2 at 3.0 mg/ml or uncoated control. Treatments were randomized between jaw quadrants. The mucoperiosteal flaps were advanced, adapted and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7 and 8 post-surgery when they were euthanized for histologic evaluation.
Jaw quadrants receiving implants coated with rhBMP-2 exhibited gradually regressing swelling that became hard to palpate disguising the contours of the implants. The histologic evaluation showed robust bone formation reaching or exceeding the implant platform. The newly formed bone exhibited characteristics of the adjoining resident Type II bone including cortex formation for sites receiving implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml. Sites receiving implants coated with rhBMP-2 at 3.0 mg/ml exhibited more immature trabecular bone formation, seroma formation and peri-implant bone remodelling resulting in undesirable implant displacement. Control implants exhibited minimal, if any, bone formation. Thus, implants coated with rhBMP-2 at 0.75, 1.5 and 3.0 mg/ml exhibited significant bone formation (height and area) compared with the sham-surgery control averaging (+/-SD) 4.4+/-0.4, 4.2+/-0.7 and 4.2+/-1.2 versus 0.8+/-0.3 mm; and 5.0+/-2.2, 5.6+/-2.2 and 7.4+/-3.5 versus 0.7+/-0.3 mm(2), respectively (p<0.01). All the treatment groups exhibited clinically relevant osseointegration.
rhBMP-2 coated onto titanium porous oxide implant surfaces induced clinically relevant local bone formation including vertical augmentation of the alveolar ridge and osseointegration. Higher concentrations/doses were associated with untoward effects.
Among dental implant design alterations, surface modifications have been by far the most investigated topic. Regarding implant surface research, the lack of hierarchical approaches relating in vitro, in vivo, clinical trials, and ex vivo analyses has hindered biomaterials scientists with clear informed rationale guidelines for implant surface design. This manuscript provides a critical hierarchical overview of the in vitro, laboratory in vivo, clinical, and ex vivo methodologies used to investigate the performance of novel biomaterials aiming to allow dental professionals to better evaluate the past, present, and future dental implant surface research. This manuscript also contains an overview of the commercially available surface texture and chemistry modifications including novel nanotechnology-based fabrication processes. Over the last decade, surface texturing has been the most utilized parameter for increasing the host-to-implant response. Recently, dental implant surfaces utilizing reduced length scale physico/chemical features (atomic and nanometric) have shown the potential to synergistically use both texture and the inclusion of bioactive ceramic components on the surface. Although surface modifications have been shown to enhance osseointegration at early implantation times, information concerning its long-term benefit to peri-implant tissues is lacking due to the reduced number of controlled clinical trials. Given the various implants/surfaces under study, the clinician should ask, founded on the basic hierarchical approach described for the in vitro, laboratory in vivo data, as well as the results of clinical studies to effectiveness before use of any dental implant.
The purpose of the present study was to evaluate the influence of different surface characteristics on bone integration of titanium implants. Hollow-cylinder implants with six different surfaces were placed in the metaphyses of the tibia and femur in six miniature pigs. After 3 and 6 weeks, the implants with surrounding bone were removed and analyzed in undecalcified transverse sections. The histologic examination revealed direct bone-implant contact for all implants. However, the morphometric analyses demonstrated significant differences in the percentage of bone-implant contact, when measured in cancellous bone. Electropolished as well as the sandblasted and acid pickled (medium grit; HF/HNO3) implant surfaces had the lowest percentage of bone contact with mean values ranging between 20 and 25%. Sandblasted implants with a large grit and titanium plasma-sprayed implants demonstrated 30-40% mean bone contact. The highest extent of bone-implant interface was observed in sandblasted and acid attacked surfaces (large grit; HCl/H2SO4) with mean values of 50-60%, and hydroxylapatite (HA)-coated implants with 60-70%. However, the HA coating consistently revealed signs of resorption. It can be concluded that the extent of bone-implant interface is positively correlated with an increasing roughness of the implant surface.
In this study we tested the effects of sodium fluoride (NaF) in serum-free cultures of human marrow stromal osteoblast-like [hMS(OB)] cells. NaF (10(-5) M) stimulated hMS(OB) cell proliferation up to 220% of control cultures. NaF alone did not increase type I collagen production, but in the presence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] (10(-9) M), NaF enhanced type I collagen production in a dose-dependent way to 300% of 1,25-(OH)2D3-treated control cultures. The production of alkaline phosphatase (ALP) and osteocalcin (bone gla protein, BGP) was also enhanced in the presence of 1,25-(OH)2D3 to 170 and 200%, respectively, of 1,25-(OH)2D3-treated controls. Our results suggest that 1,25-(OH)2D3 potentiates fluoride-mediated anabolism in hMS(OB) cell cultures and suggest that osteoblast precursors in bone marrow are targets for fluoride action.
The purpose of this study was to evaluate the histometrical and biomechanical anchorage of TiO2-blasted implants and TiO2-blasted implants coated with hydroxyapatite. The control implants were machined. Twenty-six rabbits had a total of 156 implants placed in the proximal part of the tibia. Each rabbit had a machined, a TiO2-blasted, and a TiO2-blasted, HA-coated implant placed in each tibia. After a healing period of 3 and 12 weeks, respectively, the implants placed in the right tibia were used for removal torque test, and the implants placed in the left tibia were used for histomorphometrical measurements. Preoperatively, implants from the same batches were examined topographically with a TopScan 3D system. The TiO2-blasted implants demonstrated significantly higher removal torque values than the machined implants, and they also had a significantly more irregular surface. Furthermore, significantly higher bone-to-implant contact length fractions were measured adjacent to the TiO2-blasted implants in contrast to the machined implants. The advantages of a TiO2-blasted surface were more pronounced after 3 weeks than after 12 weeks. The results demonstrated that it was possible to influence the anchorage of implants by altering the surface structure morphology. The new method with TiO2 blasting on the titanium surface improves the anchorage of implants but is not yet practicable for HA coating.
Cell adhesion is dependent on many factors, including the repertoire of extracellular matrix (ECM) proteins and their receptors, e.g. integrins, synthesized by the cell, the composition of the ECM adsorbed to the surface, and the intrinsic chemistry of the surface. Factors that govern bone cell, i.e. osteoblast, adhesion and ECM elaboration significantly influence its re-modeling into mature bone, and ultimately its ability to integrate with biomaterials used for orthopedic prostheses. In this study, we have investigated how treatment with bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor-beta (TGF-beta) superfamily that promotes ectopic bone formation, modulates the organization and expression of osteoblastic cell proteins. Specifically, we analyzed how BMP-2 treatment affects cytoskeletal components, ECM, and alpha 5 and beta 1 integrin receptor subunits in osteoblastic cells plated on Ti6A14V, a titanium alloy widely used for orthopedic implants that interacts with bone cells in vitro and in vivo. Osteoblastic cells were pre-treated with BMP-2 for 12 h prior to plating; BMP-2 treatment stimulated adhesion and proliferation of osteoblastic cells and this adhesive advantage was reflected in enhanced long-term matrix mineralization in the BMP-2 pretreated cultures. Confocal laser scanning microscopic analysis of BMP-2 treated cells showed that enhanced cytoskeletal organization and focal contact formation occurred. These changes were accompanied by a concomitant increase in the spatial organization of fibronectin, whereas vitronectin, collagen type I, osteopontin, and osteocalcin showed little change. The changes in ECM organization correlated with increased fibronectin, alpha 5 and beta 1 integrin subunit, and focal adhesion kinase (p125FAK) expression, as well as increased p125FAK phosphorylation. By confocal microscopy, the alpha 5 integrin subunit was more concentrated in lamellipodia after BMP-2 treatment. These results demonstrate that BMP-2 significantly altered osteoblastic cytoskeletal and ECM organization and enhanced expression of fibronectin and of specific integrin receptor subunits, with concomitant changes in the levels and phosphorylation of p125FAK. These effects may contribute to downstream cellular responses important for bone cell function, and growth.
To describe a model for the investigation of different phases of wound healing that are involved in the process resulting in osseointegration.
The implants used for the study of early healing had a geometry that corresponded to that of a solid screw implant with an SLA surface configuration. A circumferential trough had been prepared within the thread region (intra-osseous portion) that established a geometrically well-defined wound compartment. Twenty Labrador dogs received 160 experimental devices totally to allow the evaluation of healing between 2 h and 12 weeks. Both ground sections and decalcified sections were prepared from different implant sites.
The experimental chamber used appeared to be conducive for the study of early phases of bone formation. The ground sections provided an overview of the various phases of soft and hard tissue formation, while the decalcified, thin sections enabled a more detailed study of events involved in bone tissue modeling and remodeling. The initially empty wound chamber became occupied with a coagulum and a granulation tissue that was replaced by a provisional matrix. The process of bone formation started already during the first week. The newly formed bone present at the lateral border of the cut bony bed appeared to be continuous with the parent bone, but woven bone was also found on the SLA surface at a distance from the parent bone. This primary bone that included trabeculae of woven bone was replaced by parallel-fibered and/or lamellar bone and marrow. Between 1 and 2 weeks, the bone tissue immediately lateral to the pitch region, responsible for primary mechanical stability of the device, became resorbed and replaced with newly formed viable bone. Despite this temporary loss of hard tissue contact, the implants remained clinically stable at all times.
Osseointegration represents a dynamic process both during its establishment and its maintenance. In the establishment phase, there is a delicate interplay between bone resorption in contact regions (between the titanium body and mineralized bone) and bone formation in 'contact- free' areas. During the maintenance phase, osseointegration is secured through continuous remodeling and adaptation to function.
