Mechanism Of Osseointegration Research Articles

Enhanced differentiation of human osteoblasts on Ti surfaces pre-treated with human whole blood

Early and effective integration of a metal implant into bone tissue is of crucial importance for its long-term stability. While different material properties including surface roughness and wettability but also initial blood-implant surface interaction are known to influence this osseointegration, implications of the latter process are still poorly understood. In this study, early interaction between blood and the implant surface and how this affects the mechanism of osseointegration were investigated. For this, blood coagulation on a micro-roughened hydrophobic titanium (Ti) surface (SLA-Hphob) and on a hydrophilic micro-roughened Ti surface with nanostructures (SLActive-HphilNS), as well as the effects of whole human blood pre-incubation of these two surfaces on the differentiation potential of primary human bone cells (HBC) was assessed. Interestingly, pre-incubation with blood resulted in a dense fibrin network over the entire surface on SLActive-HphilNS but only in single patches of fibrin and small isolated fibre complexes on SLA-Hphob. On SLActive-HphilNS, the number of HBCs attaching to the fibrin network was greatly increased and the cells displayed enhanced cell contact to the fibrin network. Notably, HBCs displayed increased expression of the osteogenic marker proteins alkaline phosphatase and collagen-I when cultivated on both surfaces upon blood pre-incubation. Additionally, blood pre-treatment promoted an earlier and enhanced mineralization of HBCs cultivated on SLActive-HphilNS compared to SLA-Hphob. The results presented in this study therefore suggest that blood pre-incubation of implant surfaces mimics a more physiological situation, eventually providing a more predictive in vitro model for the evaluation of novel bone implant surfaces.

Chemical and structural analysis of the bone-implant interface by TOF-SIMS, SEM, FIB and TEM: Experimental study in animal

Although bone-anchored implants are widely used in reconstructive medicine, the mechanism of osseointegration is still not fully understood. Novel analytical tools are needed to further understand this process, where both the chemical and structural aspects of the bone-implant interface are important. The aim of this study was to evaluate the advantages of combining time-of-flight secondary ion mass spectroscopy (TOF-SIMS) with optical (LM), scanning (SEM) and transmission electron microscopy (TEM) techniques for studying the bone-implant interface of bone-anchored implants. Laser-modified titanium implants with surrounded bone retrieved after 8 weeks healing in rabbit were dehydrated and resin embedded. Three types of sample preparation were studied to evaluate the information gained by combining TOF-SIMS, SEM, FIB and TEM. The results show that imaging TOF-SIMS can provide detailed chemical information, which in combination with structural information from microscopy methods provide a more complete characterization of anatomical structures at the bone-implant interface. By investigating various sample preparation techniques, it is shown that grinded cross section samples can be used for chemical imaging using TOF-SIMS, if careful consideration of potential preparation artifacts is taken into account. TOF-SIMS analysis of FIB-prepared bone/implant cross section samples show distinct areas corresponding to bone tissue and implant with a sharp interface, although without chemical information about the organic components.

Osseointegration mechanism of novel synthetic bone substitute

Osseointegration mechanism of novel synthetic bone substitute

Titanium oral implants: surface characteristics, interface biology and clinical outcome

Bone-anchored titanium implants have revolutionized oral healthcare. Surface properties of oral titanium implants play decisive roles for molecular interactions, cellular response and bone regeneration. Nevertheless, the role of specific surface properties, such as chemical and phase composition and nanoscale features, for the biological in vivo performance remains to be established. Partly, this is due to limited transfer of state-of-the-art preparation techniques to complex three-dimensional geometries, analytical tools and access to minute, intact interfacial layers. As judged by the available results of a few randomized clinical trials, there is no evidence that any particular type of oral implant has superior long-term success. Important insights into the recruitment of mesenchymal stem cells, cell-cell communication at the interface and high-resolution imaging of the interface between the surface oxide and the biological host are prerequisites for the understanding of the mechanisms of osseointegration. Strategies for development of the next generation of material surface modifications for compromised tissue are likely to include time and functionally programmed properties, pharmacological modulation and incorporation of cellular components.

The removal torque of titanium implant inserted in rabbit femur coated with biomimetic deposited Ca–P coating

A number of experimental data on biomimetic deposition CaP (BDCaP) coating implants have reported promising outcomes by histological evaluation. But little is investigated on the role of the BDCaP coating and osseointegration mechanism by interface shear strength. To make a direct biomechanical comparison between the BDCaP coating implants and the uncoated rough titanium implants (control), a well-established animal model for implants removal torque testing was employed in rabbits, using a self-matching experimental design. All implants had an identical cylindrical screw shape without any macroscopic retentive structure. After 2, 4, 6, 8 and 12 weeks of bone healing, removal torque testing was performed to evaluate the interfacial shear strength of each implant type. The torqued implants were sputter-coated with gold for morphology observation and observed with a field-emission electron microscopy. Results showed that the interfacial shear strength of the BDCaP coating implants was similar to that of the uncoated rough implants at 2 and 4 weeks of healing. The mean removal torque values of the BDCaP coating implants were lower than those of control implants (P < 0.05) after 6 weeks of healing. The removal torque values for both types of implants revealed similar mean values after 8 and 12 weeks of healing; there were no significant difference between the two types of implants (P > 0.05). It can be concluded that the BDCaP coating implants had no beneficial effect on the interfacial shear strength at early bone healing stage.

Actin cytoskeletal organization in human osteoblasts grown on different dental titanium implant surfaces.

The understanding of the cellular basis of osteoblastic cell-biomaterial interaction is crucial to the analysis of the mechanism of osseointegration. Cell adhesion is a complex process that is dependent on the cell types and on the surface microtopography and chemistry of the substrate. We have studied the role of microtopography in modulating cell adhesion, in vitro, using a human osteoblastic cell line for the assessment of actin cytoskeletal organization. Through application of CLSM combining reflection and fluorescence, 2D or 3D images of cytoskeleton were obtained. On smooth surfaces, Ti CP machined, predominantly planar bone cells with an axial ratio of 1.1 were randomly oriented, with stress fibers running in all directions, and thin filopodia. On TiCP Osseotite surfaces the osteoblastic cells conformed to the irregular terrain of the sustrate with focal adhesion sites only established on the relative topographical peaks separated for a longer distance than in the machined surface, and defined wide lamellopodia and long filopodia, with enhanced expression of stress fibers, forming large clear focal contacts with the rough surface. The cytoskeletal organization of cells cultured on rough titanium supports an active role for the biomaterial surface in the events that govern osteoblastic cell adhesion. The results enforce the role of the rough sustrate surface in affecting osteoblastic cell adhesion and provide valuable information for the design of material surfaces that are required for the development of an appropriate osteogenic surface for osteoblastic anchorage, compared to machined surface, in dental implants.

The bone response of oxidized bioactive and non-bioactive titanium implants

A number of experimental and clinical data on so-called oxidized implants have reported promising outcomes. However, little is investigated on the role of the surface oxide properties and osseointegration mechanism of the oxidized implant. Sul [On the Bone Response to Oxidized Titanium Implants: The role of microporous structure and chemical composition of the surface oxide in enhanced osseointegration (thesis). Göteborg: Department of Biomaterials/Handicap Research, University of Göteborg, Sweden; 2002; Biomaterials 2003; 24: 3893–3907] recently proposed two action mechanisms of osseointegration of oxidized implants, i.e. mechanical interlocking through bone growth in pores/other surface irregularities (1) and biochemical bonding (2). The aim of the present study is two-fold: (i) investigating the role of the implant surface chemistry on bone responses; (ii) investigating the validity of the biochemical bonding theory of the oxidized, bioactive bone implants with specific implant surface chemistry. Two groups of oxidized implants were prepared using micro arc oxidation process and were then inserted in rabbit bone. One group consisted of magnesium ion incorporated implants (MgTiO implant), the other consisted of TiO 2 stoichiometry implants (TiO implant). Surface oxide properties of the implants were characterized with various surface analytic techniques. After 6 weeks of follow up, the mean peak values of removal torque of Mg implants dominated significantly over TiO implants ( p ⩽ 0.0001 ). Bonding failure generally occurred in the bone away from the bone to implant interface for the MgTiO implant and mainly occurred at the bone to implant interface for the TiO implant that consisted mainly of TiO 2 chemistry and significantly rougher surface as compared to the MgTiO implant. Between bone and the Mg- incorporated implant surface, ionic movements and ion concentrations gradient were detected. The current in vivo experimental data may provide positive evidence for the surface chemistry-mediated biochemical bonding theory of oxidized bioactive implants. However, the present study does not rule out potential synergy effects of the oxide thickness, micro-porous structure, crystal structure and surface roughness on improvements of bone responses to oxidized bioactive implants.

《再生医療と歯科補綴学の接点》補綴治療における再生医療のニーズと現時点での研究動向―確実かつ質の高いインプラント治療をめざして―

Appropriate dental implants are known to improve the quality of life in totally and partially edentulous patients, as well as to prevent future tooth loss, and so prosthetic treatment modalities have drastically changed recently with reconstruction therapy. However, dental implant therapy did not win the confidence of the dental community in the early developmental stage, until osseointegration between titanium and surrounding bone tissue was discovered and the modality utilizing osseointegration became reliable and produced durable treatment outcomes for long-term function. On the other hand, the biological mechanism of osseointegration has not been clarified yet and the time required for osseointegration is still long, e.g. three to four months. As well, when the implant is applied in the upper posterior region, the acquisition of osseointegration and the long-term survival of the implant are still not clinically adequate. Therefore, to reduce the time required for osseointegration and to regenerate enough alveolar bone mass in the target implantation site, the oral implant modality must be made more useful and potent as one of the treatment options for partial and total edentulism. With this background, we have studied biological strategies for reducing the time required for osseointegration and for regenerating enough alveolar bone mass, e.g., investigation of the specific genes for osseointegration between titanium and bone, nano-level surface modification of the titanium, biodegradable apatite foam for alveolar bone regeneration, application of bone formation-related growth factors with biological scaffold, and autologous cell transplantation of bone marrow derived mesenchymal stem cells. In this article, we review the current status of regenerative medicine being applied in prosthodontics and discuss our future research direction.

Mechanism of osseointegration: characterization of supporting bone with indentation testing and backscattered imaging

Dental implants that achieve “osseointegration” (rigid osseous fixation) are increasingly important for orthodontic anchorage and replacement of missing teeth. The critical determinant of endosseous implant performance is the response of the bone interface and its supporting bone to functional and therapeutic loads. Despite its importance for predicting the clinical performance of implanted devices, little is known about the mechanical properties of bone supporting dental implants. As presently defined, the mechanism of osseointegration is a very high rate of bone remodeling within about 1 mm of the implant surface. Since the interfacial bone remodels so rapidly (300–500%/yr), it never completes secondary mineralization. This results in a relatively compliant layer of incompletely mineralized lamellar bone that separates the implant from fully mineralized bone. Current evidence suggests this is a physiologic compensating mechanism for maintaining a stiff, inert metallic device in living bone. The new micromechanical methods of nanoindentation and backscatter emission (BSE) offer considerable promise for defining the material properties of the dynamic bone-implant interface. These data are essential to advancing the technology of endosseous implant anchorage for use in orthodontics and dentofacial orthopedics.

Tissue response to titanium implants in the rat maxilla: ultrastructural and histochemical observations of the bone-titanium interface.

The detailed mechanism of osseointegration, the most appropriate implant-bone interface, remains unclear in jaw tissues at the ultrastructural level in contrast to the many reports using long bones. The present study reports on tissue response to titanium-implantation on an animal model using rat maxilla. Animals were sacrificed at 1 to 28 days post-implantation and prepared tissue specimens, freed from implants by a cryofracture technique, were processed for transmission electron microscopy and histochemistry for tartrate resistant acid phosphatase activity (TRAPase). Different patterns in bone formation were recognized between lateral and base areas of implant cavities. In the lateral area with narrow gaps, bone deposition took place from the pre-existing bone towards the implant after active bone resorption by osteoclasts reactive to TRAPase. However, no distinct bone formation appeared in the lateral area where the implant had been installed close to the osteotomy margin. On the other hand, new bone formation was found at the base area without any apparent bone resorption. Interestingly, mononuclear cells reactive to TRAPase, presumably preosteoclasts, frequently occurred near preosteoblasts. Osseointegration around the implants was obtained in this model by 28 days post-implantation except for the lateral area with complete contact with implants, where the thin layer remained in contact with the implant surface. These findings indicate that ossification proceeds at different modes around the titanium implant in rat maxilla, depending on the nature of the recipient bones and the dimension of the gap between the implant and osteotomy margin.

High-resolution morphometric analysis of human osteoblastic cell adhesion on clinically relevant orthopedic alloys

Understanding the cellular basis of osteoblastic cell-biomaterial interaction is crucial to the analysis of the mechanism of osseointegration, a requirement of long-term orthopedic implant stability. Clinically, the amount of bone ingrowth is variable, and cellular parameters that influence ingrowth have yet to be clearly determined. In this study, two clinically relevant orthopedic alloys, titanium Ti6A14V (Ti) and cobalt-chrome-molybdenum (CC), were used for a comparative analysis of primary human osteoblastic cell adhesion and spreading, where cell adhesion represents the initial interaction between cellular elements and the biomaterial surface. The kinetic profile of adhesion revealed enhanced cell attachment upon rough Ti surfaces relative to rough CC. Using confocal laser scanning microscopy (CLSM), we observed that, during the first 12 h of contact with the substratum, osteoblastic cells were relatively less spread on rough Ti, whereas cells appeared elongated with multiple cellular extensions on rough CC. Focal adhesion contacts, as indicated by vinculin immunostaining, were distributed throughout the cells adhering to Ti, but were relatively sparse and localized to cellular processes on CC. Furthermore, three-dimensional CLSM reconstruction analysis indicated the presence of vinculin at all membrane-to-surface contact points on both Ti and CC. On Ti, these contact points closely followed the surface contour, whereas, on CC, they were restricted to relative topographic peaks only. Actin cytoskeletal reorganization was prominent in cells cultured on Ti, with stress fibers arranged throughout the cell body, whereas, on CC, actin filaments were sparse and localized primarily to cellular extensions. Because cell attachment mechanisms are likely to influence signal transduction and regulation of gene expression, these early differential responses of osteoblastic cells on Ti and CC may have functional implications on subsequent extracellular matrix mineralization and bone ingrowth at the cell-biomaterial interface.

Implant rehabilitation in Erdheim-Chester disease: A clinical report

Successful osseointegration of endosseous titanium implants is thought to be dependent upon close apposition of bone to the implant surface. The integration of implants in this patient was achieved despite the lipid-laden histiocytic infiltration of the bone marrow. Presumably, enough unaffected stromal cells were present to allow sufficient bone formation for osseointegration of the implant fixtures. This result invites speculation regarding both the mechanism of osseointegration and the minimum surface area of bone-implant interface necessary for achieving and maintaining osseointegration of titanium implants. This patient is periodically examined to determine if the loaded fixtures will remain clinically immobile for a prolonged period.