Effects of titanium(iv) ions on human monocyte-derived dendritic cells

Orthopaedic metal implants composed of titanium are routinely used in bone fracture repair and for joint replacement therapies. A considerable fraction of implant recipients are unable to benefit due to implant failure resulting from aseptic loosening, while others may experience cutaneous sensitivity to titanium after implantation. An adaptive immune reactivity towards titanium ions, originating from the biocorrosion of the implants, could play a role. As an initiator of the adaptive immune response, dendritic cells (DC) were studied for uptake and characteristics after titanium exposure. Energy filtered transmission electron microscopy showed uptake of titanium(iv) (Ti(iv)) ions by DCs in vitro and co-localisation with phosphorus-rich cell structures of the DC membranes (phospholipids), cytoplasm (ribosomes and phosphorylated proteins) and the nucleus (DNA). DC maturation and function were investigated by measuring cell surface marker expression by flow cytometry. After exposure, DCs showed a decrease in MHC class II (HLA-DR), co-stimulatory molecules (CD40, CD80 & CD86) and chemokine receptors (CCR) 6 and CCR7 but an increase in CCR4 after Ti(iv) treatment. However, Ti(iv) treated DCs had an increased stimulatory capacity towards allogenic lymphocytes. A Ti(iv) concentration dependant increase of IL-12p70 was observed amidst decrease of the other measured cytokines (TGF-β1 and TGF-β2). Hence, Ti(iv) alters DC properties, resulting in an enhanced T lymphocyte reactivity and deviation towards a Th1 type immune response. This effect may be responsible for the inflammatory side effects of titanium implants seen in patients.     

Improvisation and Evaluation of Laterosporulin Coated Titanium Surfaces for dental Applications: An In Vitro Investigation

Despite recent improvement in implant survival rates, there remains a significant demand for enhancing the long-term clinical efficacy of titanium (Ti) implants, particularly for the prevention of peri-implantitis. Bioactive substances such as antimicrobial peptides are emerging as effective alternatives for contemporary antimicrobial agents used in dental health care. Current research work was focused to use laterosporulins that are non-haemolytic cationic antimicrobial peptides from Brevibacillus spp. for coating commercially available Ti discs. The coated Ti surfaces were evaluated in vitro for biofilm formation by two dental plaque isolates Streptococcus gordonii strain DIGK25 and S. mutans strain DIGK119 as representatives of commensal and pathogenic streptococci respectively. The biofilm inhibition was ascertained with replicated experiments on hydroxyapatite discs and confirmed by florescence microscopy. The laterosporulin coated Ti discs showed significantly reduced biofilm formation by oral streptococci and displayed promising potential to enhance the antibacterial surface properties. Such improvised Ti surfaces may curb the menace of oral streptococcal biofilm formation on dental implants and the associated implant failures.     

Effect of heparin and alendronate coating on titanium surfaces on inhibition of osteoclast and enhancement of osteoblast function

The failure of orthopedic and dental implants has been attributed mainly to loosening of the implant from host bone, which may be due to weak bonding of the implant material to bone tissue. Titanium (Ti) is used in the field of orthopedic and dental implants because of its excellent biocompatibility and outstanding mechanical properties. Therefore, in the field of materials science and tissue engineering, there has been extensive research to immobilize bioactive molecules on the surface of implant materials in order to provide the implants with improved adhesion to the host bone tissue.In this study, chemically active functional groups were introduced on the surface of Ti by a grafting reaction with heparin and then the Ti was functionalized by immobilizing alendronate onto the heparin-grafted surface. In the MC3T3-E1 cell osteogenic differentiation study, the alendronate-immobilized Ti substrates significantly enhanced alkaline phosphatase activity (ALP) and calcium content. Additionally, nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was inhibited with the alendronate-immobilized Ti as confirmed by TRAP analysis. Real time PCR analysis showed that mRNA expressions of osteocalcin and osteopontin, which are markers for osteogenesis, were upregulated in MC3T3-E1 cells cultured on alendronate-immobilized Ti. The mRNA expressions of TRAP and Cathepsin K, markers for osteoclastogenesis, in RAW264.7 cells cultured on alendronate-immobilized Ti were down-regulated. Our study suggests that alendronate-immobilized Ti may be a bioactive implant with dual functions to enhance osteoblast differentiation and to inhibit osteoclast differentiation simultaneously.     

A novel sensor concept for optimization of loosening diagnostics in total hip replacement

The main reason for the revision of total hip replacements is aseptic loosening, caused by stress shielding and wear particle induced osteolysis. In order to detect an implant loosening early, the osseointegration of endoprosthetic implants must be measured exactly. Currently applied diagnostic methods, such as standard radiographs and clinical symptomatology, often result in an imprecise diagnosis. A novel radiation-free method to improve the diagnostic investigation of implant loosening is presented. The osseointegration of an implant can be identified using mechanical magnetic sensors (oscillators), which impinge on small membranes inside an implant component, e.g., the femoral hip stem. The maximum velocity after impingement of the oscillator depends on the osseointegration of the implant. Excitation of the oscillator is realized by a coil outside the human body. Another external coil is used to detect the velocity of the oscillator. To demonstrate the principle of the novel loosening sensor, an overdimensioned test device was designed to measure simulated loosening phases in the first experimental tests with different material layers. The overdimensioned test device of the loosening sensor showed significant differences in the various phases of fixation. Analysis of the membrane without any material layer in the case of advanced loosening resulted in a 23% higher maximum velocity compared to an attached artificial bone layer. Based on these preliminary results, the sensor system shows potential for the detection of implant loosening. Moreover, the proposed system could be used in experimental applications to determine the quality of bioactive coatings and new implant materials.     

Micro-plasma textured Ti-implant surfaces

The surface state of titanium implants modulates bone response and implant anchorage. This evidence brought implant manufacturers to switch from the standard surface refinements and implement new surface treatments for more bone apposition and enhanced interfacial strength measured by removal torque or push-out tests. Anodic plasma-chemical treatment of implant surfaces is a cost-effective process to modify surface topography and chemistry. This technique is used for structuring connected with a coating of implant surfaces. The aim of our investigations, here, is to texture the implant surface in the nanoscale without coating. Ti disks with different mechanical pre-treatment (grinded, glass blasted) were used as substrate. Micro-plasma texturing was carried out in an aqueous electrolyte. By applying a pulsed DC voltage to the specimen, micro-plasma discharge was generated in the thin steam film between immersed specimen and electrolyte. The electrical process parameter current density was varied. The micro-plasma textured Ti surfaces were characterised optically by SEM and electrochemically by CV- (for testing the corrosion parameters), CA- (to give the enlargement of the real surface) and EIS-measurement in range of 100 kHz-100 microHz. We found that the initial structure of the material surface has small or no influence on the results of the micro-plasma treatment. The properties of the thick oxide layer resulting from the plasma process are influenced by electrical process parameters. After removal of the thick oxide layer a fine, micro- and nanoscaled surface structure of the titanium remains.     

Proteome analysis of human serum proteins adsorbed onto different titanium surfaces used in dental implants

Titanium dental implants are commonly used due to their biocompatibility and biochemical properties; blasted acid-etched Ti is used more frequently than smooth Ti surfaces. In this study, physico-chemical characterisation revealed important differences in roughness, chemical composition and hydrophilicity, but no differences were found in cellular in vitro studies (proliferation and mineralization). However, the deposition of proteins onto the implant surface might affect in vivo osseointegration. To test that hypothesis, protein layers formed on discs of both surface type after incubation with human serum were analysed. Using mass spectrometry (LC/MS/MS), 218 proteins were identified, 30 of which were associated with bone metabolism. Interestingly, Apo E, antithrombin and protein C adsorbed mostly onto blasted and acid-etched Ti, whereas the proteins of the complement system (C3) were found predominantly on smooth Ti surfaces. These results suggest that physico-chemical characteristics could be responsible for the differences observed in the adsorbed protein layer.     

Instrumented hip implants: Electric supply systems

Instrumented hip implants were proposed as a method to monitor and predict the biomechanical and thermal environment surrounding such implants. Nowadays, they are being developed as active implants with the ability to prevent failures by loosening. The generation of electric energy to power active mechanisms of instrumented hip implants remains a question. Instrumented implants cannot be implemented without effective electric power systems. This paper surveys the power supply systems of seventeen implant architectures already implanted in-vivo, namely from instrumented hip joint replacements and instrumented fracture stabilizers. Only inductive power links and batteries were used in-vivo to power the implants. The energy harvesting systems, which were already designed to power instrumented hip implants, were also analyzed focusing their potential to overcome the disadvantages of both inductive-based and battery-based power supply systems. From comparative and critical analyses of the methods to power instrumented implants, one can conclude that: inductive powering and batteries constrain the full operation of instrumented implants; motion-driven electromagnetic energy harvesting is a promising method to power instrumented passive and active hip implants.     

Surface Functionalization of Orthopedic Titanium Implants with Bone Sialoprotein

Orthopedic implant failure due to aseptic loosening and mechanical instability remains a major problem in total joint replacement. Improving osseointegration at the bone-implant interface may reduce micromotion and loosening. Bone sialoprotein (BSP) has been shown to enhance bone formation when coated onto titanium femoral implants and in rat calvarial defect models. However, the most appropriate method of BSP coating, the necessary level of BSP coating, and the effect of BSP coating on cell behavior remain largely unknown. In this study, BSP was covalently coupled to titanium surfaces via an aminosilane linker (APTES), and its properties were compared to BSP applied to titanium via physisorption and untreated titanium. Cell functions were examined using primary human osteoblasts (hOBs) and L929 mouse fibroblasts. Gene expression of specific bone turnover markers at the RNA level was detected at different intervals. Cell adhesion to titanium surfaces treated with BSP via physisorption was not significantly different from that of untreated titanium at any time point, whereas BSP application via covalent coupling caused reduced cell adhesion during the first few hours in culture. Cell migration was increased on titanium disks that were treated with higher concentrations of BSP solution, independent of the coating method. During the early phases of hOB proliferation, a suppressive effect of BSP was observed independent of its concentration, particularly when BSP was applied to the titanium surface via physisorption. Although alkaline phosphatase activity was reduced in the BSP-coated titanium groups after 4 days in culture, increased calcium deposition was observed after 21 days. In particular, the gene expression level of RUNX2 was upregulated by BSP. The increase in calcium deposition and the stimulation of cell differentiation induced by BSP highlight its potential as a surface modifier that could enhance the osseointegration of orthopedic implants. Both physisorption and covalent coupling of BSP are similarly effective, feasible methods, although a higher BSP concentration is recommended.     

The BCL2 -938C>A Promoter Polymorphism Is Associated with Risk for and Time to Aseptic Loosening of Total Hip Arthroplasty

Aseptic loosening is a major cause of revision surgery of total hip arthroplasty (THA). Only few host factors affecting aseptic loosening have been identified until now, although they are urgently needed to identify and possibly treat those patients at higher risk for aseptic loosening. To determine whether the functional single nucleotide polymorphism (SNP) c.-938C>A (rs2279115), located in the promoter region of the BCL2 gene has an impact on aseptic loosening of THA we genotyped and analyzed 234 patients suffering from aseptic loosening and 231 patients after primary THA. The polymorphism is associated with risk for aseptic loosening with the CC genotype at highest risk for aseptic loosening, Odds Ratio CC vs. AA 1.93, 95%CI 1.15–3.25, p = 0.013. In contrast, low risk AA genotype carriers that still developed aseptic loosening showed a significantly shorter time to aseptic loosening than patients carrying the C allele (p = 0.004). These results indicate that the BCL2 -938C>A polymorphism influences the occurrence and course of aseptic loosening and suggests this polymorphism as an interesting candidate for prospective studies and analyses in THA registers.     

Inhibition de l'adhérence de Porphyromonas gingivalis sur la surface de titane greffé de poly(styrène sulfonate de sodium)

Dental implant-associated infections as peri-implantitis represent one of the major causes of osteointegration failures of oral implants. Adhesion of Porphyromonas gingivalis, one of the bacterial strains mainly involved in such infections, is tightly dependent on the topographical and/or physico-chemical properties of the implant surfaces. As a matter of fact, we showed that the grafting of one bioactive polymer such as poly(sodium styrene sulfonate) onto titanium implant surfaces allowed a sensitive decrease of Staphylococcus aureus adhesion (> 40%). The aim of the study consists in evaluating the adhesion of P. gingivalis onto titanium surfaces grafted with poly(sodium stryrene sulfonate) in order to elaborate implants exhibiting appropriate inhibiting properties towards the adhesion of periodontal pathogens. The grafting of poly(sodium stryrene sulfonate) onto titanium surfaces is carried out in two steps: chemical oxydation of titanium to initiate radical species then grafting of poly(sodium stryrene sulfonate) by radical polymerization. Chemical characterization of the surfaces is achieved by Fourier transformed infrared spectroscopy (FTIR). Bacterial adhesion was studied on grafted and non grafted (control) titanium surfaces, preadsorbed or not by plasmatic proteins. Protein adsorption as well as bacteria adhesion is followed by fluorescence spectroscopy by using proteins or bacteria previously labelled with fluorescence probes; the quantification of adsorption and bacteria adhesion are performed by image analysis. Results showed that protein adsorption is more important (~3 times) and that P. gingivalis adhesion is strongly inhibited (~73%) onto poly(sodium styrene sulfonate) grafted surfaces when compared to titanium control. Moreover, the inhibition of bacterial adhesion on grafted surfaces preadsorbed with plasma proteins is comparable to that observed on grafted surfaces preadsorbed with fibronectin. In conclusion, the obtained results evidenced that the grafting of titanium surface by poly(sodium styrene sulfonate) led to significant inhibition of P. gingivalis adhesion and that this inhibitory activity involved adsorbed proteins. Poly(sodium styrene sulfonate) grafted titanium surfaces present a high interest for the elaboration of oral implants in various clinical dental applications.     

A new coating method for cemented femur shaft implants--biocompatibility, stability during sterlization and adhesive strength]

The main cause of aseptic loosening of cemented stems in total hip arthroplasty is the hydrolytic degradation of the metal-cement interface. In order to prevent this debonding a new multilayer method of coating the implant surface involving the use of a silica-/silane technique to create a durable adhesive bond between metal stem and bone cement has been developed. The biocompatibility of all the elements of the multilayer system was confirmed using a human osteoblast cell culture test. For sterilization purposes, gamma irradiation with a 25 kGy effective dose proved to be the method of choice. The proven biocompatibility and successful sterilization of the coated implants are the main prerequisites for in-vivo usage. On the technical side, the bonding effectiveness of the multilayer coating system was demonstrated by the tensile test, which revealed a significant improvement in the adhesive strength of the cement-metal bond under prolonged moist conditions similar to those met with in the human body.     

Use of an absorbable membrane to position biologically inductive materials in the periprosthetic space of cemented joints

A device is presented that positions ultrahigh molecular weight polyethylene (UHMWPE) debris against periprosthetic bone surfaces. This can facilitate the study of aseptic loosening associated with cemented joint prostheses by speeding the appearance of this debris within the periprosthetic space. The device, composed of a 100 microm thick bioabsorbable membrane impregnated with 1.4 x 10(9) sub-micron particles of UHMWPE debris, is positioned on the endosteum of the bone prior to the insertion of the cemented orthopedic implant. An in vitro pullout study and an in vivo canine pilot study were performed to investigate its potential to accelerate "time to aseptic loosening" of cemented prosthetic joints. Pullout studies characterized the influence of the membrane on initial implant fixation. The tensile stresses (mean+/-std.dev.) required to withdraw a prosthesis cemented into canine femurs with and without the membrane were 1.15+/-0.3 and 1.54+/-0.01 MPa, respectively; these findings were not significantly different (p > 0.4). The in vivo pilot study, involving five dogs, was performed to evaluate the efficacy of the debris to accelerate loosening in a canine cemented hip arthroplasty. Aseptic loosening and lameness occurred within 12 months, quicker than the 30 months reported in a retrospective clinical review of canine hip arthroplasty.     

骨科假体表面涂层技术现状

由植入物界面处的相互作用可能引起无菌性松动和假体周围感染。而无菌性松动和假体周围感染仍然是一个难以治疗的问题,并且最终可能导致假体植入失败,引起严重后果。理想的植入物应能促进骨整合,防止细菌粘附,减少细菌感染。骨科植入技术主要基于生物材料的开发和使用,随着材料科学和细胞生物学的发展,已可以用新的植入物表面涂层的进展来解决这些问题。本文回顾总结了时下骨科常见的假体涂层设计和相关问题,以期为进一步研究提供借鉴。     

人工关节假体无菌性松动动物模型的快速建立

目的:人工关节置换手术发展至今,取得了非常大的成功,已在临床解决了许多终末期的关节疾患。研究表明,假体无菌性松动的患者,其假体周围处于高骨更新状态。因此骨-假体界面的早期整合对于阻止磨屑颗粒和细胞因子的迁移至关重要,而限制人工关节假体使用寿命的一个主要原因是磨屑颗粒诱导的假体无菌性松动。在本研究中,我们旨在尝试使用107个UHMWPE颗粒快速建立人工关节假体无菌性松动的兔动物模型,以便为进一步探讨假体无菌性松动的机制及防治奠定实验基础。方法:我们用雌性新西兰大白兔建立动物模型,随机均分为实验组和对照组,在两组动物的左侧胫骨髓腔内植入羟基磷灰石(hydroxyapatite,HA)涂层假体。在实验组中,分别于假体表面和膝关节腔内植入0.5×10~7超高分子量聚乙烯(Ultra-high molecular weight polyethylene,UHMWPE)颗粒。结果:同对照组相比,实验组动物的关节内压力更高、骨组织形态学参数更差、假体生物力学固定强度更低,同时,促炎细胞因子和骨更新标志均显著高于对照组。结论:我们使用很少的UHMWPE颗粒成功快速地建立了人工关节假体无菌性松动的兔动物模型,从而为今后人工关节假体无菌性松动的进一步研究奠定了实验基础。     

Molecular pathways in aseptic loosening of orthopaedic endoprosthesis

Operative joint replacement to treat disabling joint conditions secondary to degenerative and inflammatory arthritides has become one of the most efficacious and cost-effective procedures to relieve pain and restore joint function. However, prosthetic implants are not built to last forever and osteolysis and aseptic loosening has been associated with prosthetic arthroplasties since their introduction. The functional life of a synthetic joint is influenced by many factors including the material of the implant, operation procedures and the surgeon involved, as well as patient-related factors. Although promising developments have been achieved in this field, more than 10% of all implants still have to undergo operative revision within 15 years after the initial operation. Failure due to sepsis, fractures and dislocations has become rare; premature loosening of implants on the other hand is becoming much more important. Prosthetic loosening without concurrent infection or trauma is called aseptic loosening. It is generally accepted that small particles ("wear debris") and activated macrophages play a key role in aseptic loosening. The pathophysiology of this condition, however, is still not very well characterized. In this article, we review the molecular mechanisms and signal pathways that were unravelled as responsible factors for loosening orthopaedic implants. Finally, we discuss possible novel strategies for future therapeutic approaches.     

Mechanical loading releases osteoclastogenesis-modulating factors through stimulation of the P2X7 receptor in hematopoietic progenitor cells

Mechanical instability of bone implants stimulate osteoclast differentiation and peri-implant bone loss, leading to prosthetic loosening. It is unclear which cells at the periprosthetic interface transduce mechanical signals into a biochemical response, and subsequently facilitate bone loss. We hypothesized that mechanical overloading of hematopoietic bone marrow progenitor cells, which are located near to the inserted bone implants, stimulates the release of osteoclast-inducing soluble factors. Using a novel in vitro model to apply mechanical overloading, we found that hematopoietic progenitor cells released adenosine triphosphate (ATP) after only 2 min of mechanical loading. The released ATP interacts with its specific receptor P2X7 to stimulate the release of unknown soluble factors that inhibit (physiological loading) or promote (supraphysiological loading) the differentiation of multinucleated osteoclasts derived from bone marrow cultures. Inhibition of ATP-receptor P2X7 by Brilliant Blue G completely abolished the overloading-induced stimulation of osteoclast formation. Likewise, stimulation of P2X7 receptor on hematopoietic cells by BzATP enhanced the release of osteoclastogenesis-stimulating signaling molecules to a similar extent as supraphysiological loading. Supraphysiological loading affected neither gene expression of inflammatory markers involved in aseptic implant loosening (e.g., interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, and PTGES2) nor expression of the osteoclast modulators receptor activator of nuclear factor κ-Β ligand and osteoprotegerin. Our findings suggest that murine hematopoietic progenitor cells are a potential key player in local mechanical loading-induced bone implant loosening via the ATP/P2X7-axis. Our approach identifies potential therapeutic targets to prevent prosthetic loosening.     

An Improved Mechanical Testing Method to Assess Bone-implant Anchorage

Recent advances in material science have led to a substantial increase in the topographical complexity of implant surfaces, both on a micro- and a nano-scale. As such, traditional methods of describing implant surfaces - namely numerical determinants of surface roughness - are inadequate for predicting in vivo performance. Biomechanical testing provides an accurate and comparative platform to analyze the performance of biomaterial surfaces. An improved mechanical testing method to test the anchorage of bone to candidate implant surfaces is presented. The method is applicable to both early and later stages of healing and can be employed for any range of chemically or mechanically modified surfaces - but not smooth surfaces. Custom rectangular implants are placed bilaterally in the distal femora of male Wistar rats and collected with the surrounding bone. Test specimens are prepared and potted using a novel breakaway mold and the disruption test is conducted using a mechanical testing machine. This method allows for alignment of the disruption force exactly perpendicular, or parallel, to the plane of the implant surface, and provides an accurate and reproducible means for isolating an exact peri-implant region for testing.     

Lysophosphatidic acid stimulates nuclear and cytoplasmic maturation of golden hamster immature oocytes in vitro via cumulus cells

Lysophosphatidic acid (LPA), a member of the phospholipid autacoid family, is induced in incubated human follicular fluid by lysophospholipase D. It is well known that LPA functions as a growth factor and the hypothesis that LPA in human follicular fluid takes a part in meiosis of oocytes is quite plausible. We studied the effects of LPA on the maturation of golden hamster immature oocytes in vitro. Hamster oocytes with a germinal vesicle were cultured in Tyrode's albumin lactate pyruvate (TALP) medium with 10(-5) M LPA, 10 ng/ml epidermal growth factor (EGF), 30 ng/ml insulin-like growth factor-1, 1 ng/ml tumor growth factor-alpha or 1 ng/ml basic fibroblast growth factor. The nuclear maturation rates in the LPA and EGF groups were significantly higher than in the control group and the other growth factors did not show any stimulatory effect (LPA group; 74.3% [75/101], EGF group; 82.4% [89/108] vs. control group; 60.2% [59/98], p < 0.05, p < 0.01, respectively). When the cells of cumulus were removed, EGF and LPA did not increase the nuclear maturation rates. Cotreatment EGF and LPA did not significantly enhance the stimulatory effect observed with LPA alone on maturation in vitro. The penetration rate determined by the zona-free hamster oocyte test was significantly higher in the LPA group than in the control group (26.7% vs. 13.2%, p < 0.05) and was comparable with that of oocytes matured in vivo. In conclusion, LPA stimulates the nuclear and cytoplasmic maturation of hamster immature oocytes via cumulus cells.     

Bacterial Pathogen-associated Molecular Patterns Stimulate Biological Activity of Orthopaedic Wear Particles by Activating Cognate Toll-like Receptors

Aseptic loosening of orthopaedic implants is induced by wear particles generated from the polymeric and metallic components of the implants. Substantial evidence suggests that activation of Toll-like receptors (TLRs) may contribute to the biological activity of the wear particles. Although pathogen-associated molecular patterns (PAMPs) produced by Gram-positive bacteria are likely to be more common in patients with aseptic loosening, prior studies have focused on LPS, a TLR4-specific PAMP produced by Gram-negative bacteria. Here we show that both TLR2 and TLR4 contribute to the biological activity of titanium particles with adherent bacterial debris. In addition, lipoteichoic acid, a PAMP produced by Gram-positive bacteria that activates TLR2, can, like LPS, adhere to the particles and increase their biological activity, and the increased biological activity requires the presence of the cognate TLR. Moreover, three lines of evidence support the conclusion that TLR activation requires bacterially derived PAMPs and that endogenously produced alarmins are not sufficient. First, neither TLR2 nor TLR4 contribute to the activity of “endotoxin-free” particles as would be expected if alarmins are sufficient to activate the TLRs. Second, noncognate TLRs do not contribute to the activity of particles with adherent LPS or lipoteichoic acid as would be expected if alarmins are sufficient to activate the TLRs. Third, polymyxin B, which inactivates LPS, blocks the activity of particles with adherent LPS. These results support the hypothesis that PAMPs produced by low levels of bacterial colonization may contribute to aseptic loosening of orthopaedic implants.     

Mechanics and electrostatics of the interactions between osteoblasts and titanium surface

Due to oxidation and adsorption of chloride and hydroxyl anions, the surface of titanium (Ti) implants is negatively charged. A possible mechanism of the attractive interaction between the negatively charged Ti surface and the negatively charged osteoblasts is described theoretically. It is shown that adhesion of positively charged proteins with internal charge distribution may give rise to attractive interaction between the Ti surface and the osteoblast membrane. A dynamic model of the osteoblast attachment is presented in order to study the impact of geometrically structured Ti surfaces on the osteoblasts attachment. It is indicated that membrane-bound protein complexes (PCs) may increase the membrane protrusion growth between the osteoblast and the grooves on titanium (Ti) surface and thereby facilitate the adhesion of osteoblasts to the Ti surface. On the other hand, strong local adhesion due to electrostatic forces may locally trap the osteoblast membrane and hinder the further spreading of osteointegration boundary. We suggest that the synergy between these two processes is responsible for successful osteointegration along the titanium surface implant.