Biocompatibility of titanium implants modified by microarc oxidation and hydroxyapatite coating

A thin hydroxyapatite (HA) layer was coated on a microarc oxidized titanium (MAO-Ti) substrate by means of the sol-gel method. The microarc oxidation (anodizing) enhanced the biocompatibility of the Ti, and the bioactivity was improved further by the sol-gel HA coating on the anodized Ti. The HA sol was aged fully to obtain a stable and phase-pure HA, and the sol concentration was varied to alter the coating thickness. Through the sol-gel HA coating, the Ca and P concentrations in the coating layer increased significantly. However, the porous morphology and roughness of the MAO-Ti was altered very little by the sol-gel treatment. The proliferation and alkaline phosphatase (ALP) activity of the osteoblast-like cells on the MAO/HA sol-gel-treated Ti were significantly higher than those on the MAO-Ti without the HA sol-gel treatment.     

Facile surface functionalization with glycosaminoglycans by direct coating with mussel adhesive protein

The use of mussel adhesive proteins (MAPs) as a surface coating for cell adhesion has been suggested due to their unique properties of biocompatibility and effective adhesion on diverse inorganic and organic surfaces. The surface functionalization of scaffolds or implants using extracellular matrix (ECM) molecules is important for the enhancement of target cell behaviors such as proliferation and differentiation. In the present work, we suggest a new, simple surface functionalization platform based on the charge interactions between the positively charged MAP linker and negatively charged ECM molecules, such as glycosaminoglycans (GAGs). MAP was efficiently coated onto a titanium model surface using its adhesion ability. Then, several GAG molecules, including hyaluronic acid (HA), heparin sulfate (HS), chondroitin sulfate (CS), and dermatan sulfate (DS), were effectively immobilized on the MAP-coated surfaces by charge interactions. Using HA as a model GAG molecule, we found that the proliferation, spreading, and differentiation behaviors of mouse preosteoblast cells were all significantly improved on MAP/HA-layered titanium. In addition, we successfully constructed a multilayer film on a titanium surface with oppositely charged layer-by-layer coatings of MAP and HA. Collectively, our simple MAP-based surface functionalization strategy can be successfully used for the efficient surface immobilization of negatively charged ECM molecules in various tissue engineering and medical implantation applications.     

Immune response against polyester implants is influenced by the coating substances

The aim of this study was to evaluate the influence of the coating of polymer implants upon the individual humoral immune response to the polymer matrix. Intramuscular implantation and explantation of samples from three different polyester vascular prostheses coated with collagen, gelatin, or human serum albumin was performed in LEW.1A rats and subsequently compared to sham operated control animals. Antibodies in serum samples were detected by means of enzyme immunoassays employing particles of pure polyester and the respective prosthesis, or solid phase bound coating substances as targets. In contrast to the controls, all animals with implants demonstrated a high antipolyester antibody response with a broad individual variability graduated according to the prosthesis coatings: gelatin > albumin > collagen. This was further significantly increased after the second implantation/first explantation and declined following the last explantation. Only animals with albumin-coated implants revealed specific antibodies to the coating as well as the strongest overall immunological reaction against the prosthesis already on day 8. Specificity of polymer antibodies was demonstrated by competitive inhibition of median antibody binding. Our results showed a specific immune reaction as a result of the applied polymer, which varied due to the surface-coating and individual factors.     

The effects of cyclooxygenase-2 inhibitors on urological cancer cells

Cyclooxygenase (COX)-2 plays an important role in the development of various cancers due to its angiogenic function. We have demonstrated that the expression of COX-2 was up-regulated in human renal cell carcinoma (RCC), bladder tumor (BT) and prostate cancer (PC). In this study, we examined the effects of COX-2 inhibitors on cell proliferation in RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. COX-2 inhibitors did not induce a reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, showed no inhibition of cell proliferation using COX-2 inhibitors. COX-2 inhibitors could not stop the growth of RCC, BT and PC cells. Typical characteristics of apoptosis, i.e. chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies) and cytoplasmic condensation, did not occur. Although the expression of COX-2 was up-regulated in human RCC, BT and PC tissues, COX-2 inhibitors have only slight anti-proliferative effects against RCC, BT and PC cells through differentiation. Thus, using only down-regulation of arachidonic acid (AA) metabolizing enzyme, COX may be an unsuccessful approach in providing new anti-cancer therapies.     

Blood-compatible biomaterials by surface coating with a novel antithrombin-heparin covalent complex.

Covalent antithrombin-heparin complex (ATH) was covalently grafted to a polycarbonate urethane (Corethane) endoluminal graft (a kind gift of Corvita Corporation) after being activated using 0.3% m/m NaOCl in 0.15 M phosphate pH 6.0. ATH graft density (1.98 x 10(-7) mol/m2) was 6 times the maximum amount of unfractionated heparin (UFH) that could be bound to polycarbonate urethane surfaces. Surface-bound ATH could be stored in sterile 0.15 M NaCl at 4 degrees C for at least 2 months with good antithrombotic activity before being implanted into rabbits. Analysis of ATH-coated tubing showed that it contained significant direct thrombin inhibitory activity. In vivo testing in a rabbit model was compared to non-activated non-coated surfaces, activated-non-coated surfaces, hirudin-coated surfaces and antithrombin (AT)-coated surfaces. The weight of the clot generated in the ATH-coated graft tubing was significantly less than the weight of the clot generated within the hirudin-coated graft (p = 0.03 with a 1-tailed Student's t test). The anticoagulant nature of ATH grafts in vivo was shown to be due to bound ATH because boththe AT-coated surfaces and non-coated but activated surfaces showed similar thromboresistant efficacy to that of untreated material (ANOVA; p < 0.05). Apart from the direct antithrombin activity that contributed to much of the prolonged patency in vivo, surface-bound ATH likely catalyzed AT inhibition of thrombin, as evidenced by a significant number of 125I-AT binding sites (> or = 1.5 x 10(-8) mol/m2). Thus, ATH appears to be a good candidate for coating cardiovascular devices, such as endoluminal grafts, with high levels of substitution and significant long-term blood-compatibility.     

Characterization and optimization of experimental variables within a reproducible bladder encrustation model and in vitro evaluation of the efficacy of urease inhibitors for the prevention of medical device-related encrustation

This study presents a reproducible, cost-effective in vitro encrustation model and, furthermore, describes the effects of components of the artificial urine and the presence of agents that modify the action of urease on encrustation on commercially available ureteral stents. The encrustation model involved the use of small-volume reactors (700 mL) containing artificial urine and employing an orbital incubator (at 37 degrees C) to ensure controlled stirring. The artificial urine contained sources of calcium and magnesium (both as chlorides), albumin and urease. Alteration of the ratio (% w/w) of calcium salt to magnesium salt affected the mass of encrustation, with the greatest encrustation noted whenever magnesium was excluded from the artificial urine. Increasing the concentration of albumin, designed to mimic the presence of protein in urine, significantly decreased the mass of both calcium and magnesium encrustation until a plateau was observed. Finally, exclusion of urease from the artificial urine significantly reduced encrustation due to the indirect effects of this enzyme on pH. Inclusion of the urease inhibitor, acetohydroxamic acid, or urease substrates (methylurea or ethylurea) into the artificial medium markedly reduced encrustation on ureteral stents. In conclusion, this study has described the design of a reproducible, cost-effective in vitro encrustation model. Encrustation was markedly reduced on biomaterials by the inclusion of agents that modify the action of urease. These agents may, therefore, offer a novel clinical approach to the control of encrustation on urological medical devices.     

Calcium-phosphate surface coating by casting to improve bioactivity of titanium

In order to improve the bioactivity of titanium, an original surface treatment was attempted with the use of a casting technique was attempted. Pure titanium was cast into a special graphite mold in which the cavity wall was coated with hydroxyapatite (HA) powder. According to analyses of X-ray diffraction and EDX, the existence of HA and CaO and uptake of Ca and P on the surface of the titanium castings were identified. By immersing the specimen in Hank's solution, the concentrations of Ca and P on the surface increased with immersion time, and the formation of a thin layer with characteristics of spherical HA precipitates was observed after 1 week. The concentrations of Ca and P elements and the Ca/P ratio on the HA layer increased with immersion time. The formation of the HA layer on the titanium cast by this treatment was significantly accelerated compared with pure titanium. The present surface treatment of Ti is expected to improve early bone fixation of Ti implants.     

Bioactive glass surface for fiber reinforced composite implants via surface etching by Excimer laser

Biostable fiber-reinforced composites (FRC) prepared from bisphenol-A-glycidyldimethacrylate (BisGMA)-based thermosets reinforced with E-glass fibers are promising alternatives to metallic implants due to the excellent fatigue resistance and the mechanical properties matching those of bone. Bioactive glass (BG) granules can be incorporated within the polymer matrix to improve the osteointegration of the FRC implants. However, the creation of a viable surface layer using BG granules is technically challenging. In this study, we investigated the potential of Excimer laser ablation to achieve the selective removal of the matrix to expose the surface of BG granules. A UV–vis spectroscopic study was carried out to investigate the differences in the penetration of light in the thermoset matrix and BG. Thereafter, optimal Excimer laser ablation parameters were established. The formation of a calcium phosphate (CaP) layer on the surface of the laser-ablated specimens was verified in simulated body fluid (SBF). In addition, the proliferation of MG63 cells on the surfaces of the laser-ablated specimens was investigated. For the laser-ablated specimens, the pattern of proliferation of MG63 cells was comparable to that in the positive control group (Ti6Al4V). We concluded that Excimer laser ablation has potential for the creation of a bioactive surface on FRC-implants.     

Application of PVD TiN coating to Co-Cr-Mo based surgical implants

The requirements for successful joint arthroplasty are particularly exacting; a balanced combination of mechanical properties together with good biocompatibility are essential. Co-Cr based alloys have been used for many years on account of their relative inertness, good load bearing properties and excellent wear resistance. There is, however, concern that a slow accumulation of metal ions such as cobalt and chromium can lead to adverse clinical reactions; modern cementless fixation techniques may exacerbate this problem.

In an attempt to reduce the release of potentially harmful metal ions from Co-Cr-Mo based surgical implants, a thin coating of TiN has been applied via Physical Vapour Deposition (PVD). In vitro corrosion performance has been investigated using electrochemical techniques, and also by atomic absorption analysis.

The release of cobalt and chromium ions is shown to be reduced by the presence of the TiN coating, and these results are discussed in terms of the electrochemistry and microstructure of the coating and substrate.     

Enhancement of bony in-growth to metal implants by combining controlled hydroxyapatite coating and heat treatment

The rate of bony in-growth to heat-treated and controlled hydroxyapatite metal implants made of either titanium alloy (Ti-6Al-4V) or stainless steel (SS) 316L inserted to the medullar canal of the femur in rats was investigated. It was found that while partial coverage of hydroxyapatite (HA) did not cause a significant elevation of their bonding strength when compared with nonheated implants, HA, and heat treatment caused a significant (p < 0.01) elevation of 3.1-fold in the bonding strength of the implants to the host bone. A similar phenomenon to that found for the titanium alloy implants was found to be true for the SS implants as well. It is concluded that the novel approach presented in this article, that is, to heat treat implants as well as controlled partial coating of them by HA, prior to their insertion to host bone, produce an enhancement of bone growth to metal implants greater than utilization of each method alone. Our findings may be used to further enhance bony in-growth to metal implants in several clinical settings, producing avid implants with superior integration capabilities.     

Biomechanical and histomorphometric study of dental implants with different surface characteristics

The aim of this study was to investigate the early bone response to the titanium dental implants with different surface characteristics using the rabbit tibia model. Calcium metaphosphate coated, anodic oxidized, hydroxyapatite particle-blasted, and turned (control) surfaces were compared. Surface topography was evaluated by field emission scanning electron microscope and optical interferometer. Eighteen rabbits received 72 implants in the tibia. Resonance frequency was analyzed every week for 6 weeks. Removal torque values were measured 2 and 6 weeks after placement. The implant-bone interfaces were directly observed by light microscope and bone-to-implant contact ratios were measured 2 and 6 weeks after insertion. All the surface-modified implants showed superior initial bone responses to the control. No significant differences were found among the surface-modified groups. Data suggest that various surface modification methods can provide favorable bone responses for early functioning and healing of dental implants.     

Prospects of using titanium nickelide implants with modified surface in dental implantology

Corrosion resistance and biocompatibility of 60 specimens of titanium nickelide with modified surfaces implanted into spongy bone were studied in rabbit experiments. Specimens modified by molybdenum ions exhibited high inertness and favorable tissue reaction. No accumulation of nickel and titanium ions in animal organs was detected. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 145, No. 6, pp. 707–713, June, 2008     

In vivo behavior and mechanical stability of surface-modified titanium implants by plasma spray coating and chemical treatments

The geometric design and chemical compositions of an implant surface may have an important part in affecting early implant stabilization and influencing tissue healing. In this study, in vivo behavior and mechanical stability in implants of three surface designs, which were smooth surface (SS), rough titanium (Ti) surface by plasma spray coating (PSC), and alkali- and heat-treated (AHT) Ti surface after plasma spray coating, were compared by histological and mechanical analyses. Surface morphologies of the implants were observed by optical microscopy and scanning electron microscopy. Chemical compositional surface changes were investigated by energy dispersive spectroscopy. The implants were inserted transversely in a dog thighbone and evaluated at 4 weeks of healing. At 4 weeks of healing after implantation in bone, the healing tissue was more extensively integrated with an AHT implant than with the implants of smooth (SS) and/or rough Ti surfaces (PSC). The bone bonding strength (pull-out force) between living bone and implant was observed by a universal testing machine. At 4 weeks' healing after implant placement in bone, the pull-out forces of the SS, PSC, and AHT implants were 235 (+/-34.25), 710 (+/-142.25), and 823 (+/-152.22) N, respectively. Histological and mechanical data demonstrate that appropriate surface design selection can improve early bone growth and induce an acceleration of the healing response, thereby improving the potential for implant osseointegration.     

Improved biological performance of Ti implants due to surface modification by micro-arc oxidation

The surface of a titanium (Ti) implant was modified by micro-arc oxidation (MAO) treatment. A porous layer was formed on the Ti surface after the oxidation treatment. The phase and morphology of the oxide layer were dependent on the voltage applied during the oxidation treatment. With increasing voltage, the roughness and thickness of the film increased and the TiO(2) phase changed from anatase to rutile. During the MAO treatment, Ca and P ions were incorporated into the oxide layer. The in vitro cell responses of the specimen were also dependant on the oxidation conditions. With increasing voltage, the ALP activity increased, while the cell proliferation rate decreased. Preliminary in vivo tests of the MAO-treated specimens on rabbits showed a considerable improvement in their osseointegration capability as compared to the pure titanium implant.     

Cellular compatibility of highly degradable bioactive ceramics for coating of metal implants

Resorbable ceramics can promote the bony integration of implants. Their rate of degradation should ideally be synchronized with bone regeneration. This study examined the effect of rapidly resorbable calcium phosphate ceramics 602020, GB14, 305020 on adherence, proliferation and morphology of human bone-derived cells (HBDC) in comparison to β-TCP. The in vitro cytotoxicity was determined by the microculture tetrazolium (MTT) assay. HBDC were grown on the materials for 3, 7, 11, 15 and 19 days and counted. Cell morphology, cell attachment, cell spreading and the cytoskeletal organization of HBDC cultivated on the substrates were investigated using laser scanning microscopy and environmental scanning electron microscopy. All substrates supported sufficient cellular growth for 19 days and showed no cytotoxicity. On each material an identical cell colonisation of well communicating, polygonal, vital cells with strong focal contacts was verified. HBDC showed numerous well defined stress fibres which give proof of well spread and strongly anchored cells. Porous surfaces encouraged the attachment and spreading of HBDC. Further investigations regarding long term biomaterial/cell interactions in vitro and in vivo are required to confirm the utility of the new biomaterials.     

Fluoroapatite glass-ceramic coating on alumina: surface behavior with biological fluids

The results of a surface analysis performed on a fluoroapatite-based glass ceramic (SAF) also coating a full-density alpha-alumina substrate (SAF-alumina coating) are presented. These two materials have also been evaluated after soaking in simulated body fluid to understand their ability to induce hydroxyapatite growth on them. Aiming to understand the fluoroapatite glass-ceramic interaction with some plasma proteins, in the second part of this study, fibronectin, albumin, immunoglobulin G, IgA, and complement factor C3c SAF binding have been evaluated; surface activity on complement activation has also been quantified. SAF-alumina coating provides good sites for the nucleation and growth of an apatite layer, equivalent to the mineral component of bone and binds preferentially plasma fibronectin, which is well known to enhance cell adhesion and spreading. Moreover, SAF-alumina coating reduces alumina complement activation directly or via reduced IgA binding. Alumina was shown to bind the same C3 fragments as Zymosan, used as complement activating control, and to induce increased levels of serum soluble iC3b and Bb. A mechanical resistant material with enhanced bioactivity, bone integration, and reduced inflammatory potential respect to alumina has been obtained.     

Structure and surface of TiNi human implants.

The surface and the "bulk" structure of TiNi implants were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoemission spectroscopy (XPS), and scanning Auger microprobe analysis (AES). TiNi implants were compared with otherwise identically prepared non-implanted specimens, and sputter-cleaned and reoxidized samples. Non-implanted and implanted samples had essentially the same surface topography and microstructure. Ti, O, and C were the dominant elements detected on the surface. Trace amounts (approximately 1 at%) of Ni and Ca, N, Si, B, and S were also detected. Ti was present as TiO2 on the surface, while nickel was present in metallic form. A significant difference in Ni peak intensity was observed when retrieved or non-implanted control samples (a very low nickel content) were compared with sputter-cleaned and reoxidized samples (well-detected nickel). It is evident that the method of passivation is crucial for nickel loosening. No major changes occurred in the TiNi samples bulk structure or in the surface oxide during the implantation periods investigated.     

钛合金表面抗菌涂层：抗菌能力及生物相容性

背景：钛合金材料因具有良好的生物相容性、耐腐蚀性和综合力学性能被广泛用于临床,如何赋予其优良的抗菌性以应对内植物相关感染是近年来的研究热点。 目的：综述了钛合金表面抗菌涂层的原理、技术、分类及优缺点。 方法：由第一作者检索1990年1月至2014年1月Scopus 数据库、中国科技期刊数据库(重庆维普)相关文献,检索关键词为“Titanium alloy,Plant,Antibacterial,Coating;钛合金,内植物,抗菌,涂层”。 结果与结论：根据涂层的种类可将其分为抗生素类涂层、非抗生素类有机抗菌剂涂层、无机抗菌剂类涂层、抗黏附性涂层、抗菌生物活性聚合物涂层,各种涂层均具有较好的生物相容性,但也有各自的局限,目前对抗菌涂层的研究主要集中于：如何增强抗菌涂层与基体的结合力,并获得良好的抗菌性、生物相容性、高耐磨性、持久性是需要研究的关键问题;抗菌相结构、分布对于细菌定植的研究,无论是合金整体添加抗菌元素还是表面涂层型钛合金,抗菌相的结构、分布是影响抗菌性能的关键因素。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

The effect of hydroxyapatite coating on bony ingrowth into grooved titanium implants

This study was undertaken to investigate the relative importance of a hydroxyapatite (HA) coating and the macrotexture of titanium implants to the quality of bony ingrowth and fixation. Various types of titanium cylinders were implanted into the cancellous bone of the intercondylar region of the distal femur of the dog. The animals were sacrificed at intervals post-implantation and the implants were evaluated histologically for amount of bony ingrowth and mechanically by the means of a push-out test. Our results demonstrated that when grooved titanium implants are used, the addition of HA coating significantly improved the biologic fixation. In addition, a groove depth of 1 mm was found to give significantly better fixation than 2 mm. When compared to implants with traditional, beads-coated porous surfaces, HA-coated grooved titanium implants were found to show better fixation at 4 weeks after implantation, but, significantly inferior fixation at 12 weeks after implantation. We concluded that while a groove depth of 1 mm was optimal in HA-coated, grooved titanium implants, they remain inferior to beads-coated titanium implants with respect to longer-term fixation. More research needs to be addressed at improving the macrotexture environment of grooved implants to enhance long-term bony ingrowth.     

Laser processing of bioactive tricalcium phosphate coating on titanium for load-bearing implants

Laser-engineered net shaping (LENS), a commercial rapid prototyping (RP) process, was used to coat titanium with tricalcium phosphate (TCP) ceramics to improve bone cell-materials interactions. During LENS coating process, the Nd:YAG laser melts the top surface of Ti substrate in which calcium phosphate powder is fed to create a TCP-Ti composite layer. It was found that an increase in laser power and/or powder feed rate increases the thickness of the coating. However, coating thickness decreased with increasing laser scan speed. TCP coating showed columnar titanium grains at the substrate side of the coating and transitioned to equiaxed titanium grains at the outside. When the scan speed was reduced from 15 to 10mms(-1), coating hardness increased from 882+/-67 to 1049+/-112Hv due to an increase in the volume fraction of TCP in the coating. Coated surfaces showed uniformly distributed TCP particles and X-ray diffraction data confirmed the absence of any undesirable phases, while maintaining a high level of crystallinity. The effect of TCP coating on cell-material interaction was examined by culturing osteoprecursor cells (OPC1) on coated surfaces. The results indicated that TCP coating had good biocompatibility where OPC1 cells attached and proliferated on the coating surface. The coating also initiated cell differentiation, ECM formation and biomineralization.