Search

Background/aims: Accumulating evidence demonstrates the superior osteoinductivity of tantalum (Ta) to that of titanium (Ti); however, the mechanisms underlying these differences are unclear. Thus, the objective of the present study was to examine the effects of Ta and Ti surfaces on osteogenesis using rat bone mesenchymal stromal cells (rBMSCs) as a model., Methods: Ta and Ti substrates were polished to a mirror finish to minimize the influences of structural factors, and the intrinsic surface effects of the two materials on the integrin α5β1/mitogen-activated protein kinases 3 and 1 (ERK1/2) cascade-mediated osteogenesis of rBMSCs were evaluated. Alkaline phosphatase (ALP) activity, Alizarin Red staining, real-time polymerase chain reaction, and western blot assays of critical osteogenic markers were conducted to evaluate the effects of the two substrates on cell osteogenesis. Moreover, the role of the integrin α5β1/ERK1/2 pathway on the osteoinductive performance of Ta and Ti was assessed by up- and down-regulation of integrin α5 and β1 with RNA interference, as well as through ERK1/2 inhibition with U0126., Results: Osteogenesis of rBMSCs seeded on the Ta surface was superior to that of cells seeded on the Ti surface in terms of ALP activity, extracellular matrix calcification, and the expression of integrin α5, integrin β1, ERK1/2, Runt-related transcription factor 2, osteocalcin, collagen type I, and ALP at both the mRNA and protein levels. Moreover, down-regulation of integrin α5 or integrin β1, or ERK1/2 inhibition severely impaired the osteoblastic differentiation on the Ta surface. By contrast, over-expression of integrin α5 or integrin β1 improved osteogenesis on the Ti substrates, while subsequent ERK1/2 inhibition abrogated this effect., Conclusion: The integrin α5β1/ERK1/2 pathway plays a crucial role in regulating rBMSCs osteogenic differentiation; thus, the greater ability of a Ta surface to trigger integrin α5β1/ERK1/2 signaling may explain its better osteoinductivity. The different effects of Ta and Ti surfaces on rBMSC osteogenesis are considered to be related to the conductive behaviors between integrin α5β1 and the oxides spontaneously formed on the two metals. These results should facilitate the development of engineering strategies with Ta and Ti surfaces for improved osteogenesis in endosteal implants., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

The aim of the present study was to determine the correlation between bone volume density (BV/TV) around a titanium implant determined by micro-computed tomography (micro-CT) and bone area density (BA/TA) measurements obtained using histomorphometry. An intramedullary rat femur implant model was evaluated to compare raw titanium implants with plasma electrolytic oxidation (PEO)-coated titanium implants. Titanium and PEO-treated titanium pins were inserted into rat femurs under general anesthesia. The animals were sacrificed and femurs harvested at 0, 2, 4 and 6 weeks, and subsequently, histomorphometry and micro-CT were performed. BV/TV and BA/TA values were strongly and positively correlated at all time points and locations (with all correlation coefficients being >0.8 and with P < 0.001). BV/TV and BA/TA were significantly higher proximal to the growth plate than distal to the growth plate, with estimated differences of 14.10% (P < 0.001) and 11.95% (P < 0.001), respectively. BV/TV and BA/TA were significantly higher on the PEO-coated surface than on the raw titanium surface, with estimated differences of 3.20% (P = 0.044) and 4.10% (P = 0.018), respectively. Therefore, quantitative micro-CT analysis of BV/TV is correlated with BA/TA determined by histomorphometry when artifacts around titanium implants are minimized by a region of interest modification.

Modulating immune response to biomaterials through changing macrophage polarization has been proven to be a promising strategy to elicit beneficial outcomes in tissue repair. The objective of this study was to evaluate the response of macrophage polarization to titanium doped with magnesium (0.1~0.35%), which was prepared through the magnesium plasma immersion ion implantation (Mg PIII) technique. The M1/M2 polarization profile of macrophages was investigated using a murine cell line RAW 264.7 in vitro and a murine air pouch model in vivo. Our results demonstrated that the Mg PIII-treated titanium induced a higher percentage of M2 macrophages and higher concentrations of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10. Genes encoding two growth factors, bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) were up-regulated, thus indicating the ability of the M2 phenotype to promote wound healing. The nuclear factor κB (NF-κB) signalling pathway was down-regulated. In vivo the Mg PIII -treated titanium elicited a similar effect on macrophage polarization and induced thinner fibrous capsule formation and a decrease in infiltrated cells. These results indicate that Mg PIII treatment has the immunomodulatory potential to elicit the pro-healing M2-polarized macrophage phenotype, thus providing new insight into the development of immunomodulatory biomaterials.

Since the use of systemic antibiotics for preventing acute biomaterial-associated infections (BAIs) may build up bacterial resistance and result in huge medical costs and unpredictable mortality, new precaution strategies are required. Here, it demonstrated that titanium armed with a nano-thick calcium oxide layer was effective on averting methicillin-resistant Staphylococcus aureus (MRSA) infections in rabbits. The calcium oxide layer was constructed by, firstly, injecting of metallic calcium into titanium via a plasma immersion ion implantation process, and then transforming the outer most surface into oxide by exposing to the atmosphere. Although the calcium oxide armed titanium had a relative low reduction rate (~74%) in growth of MRSA in vitro, it could markedly promote the osteogenic differentiation of bone marrow stem cells (BMSCs), restore local bone integration against the challenge of MRSA, and decrease the incidence of MRSA infection with a rate of 100% (compared to the titanium control). This study demonstrated for the first time that calcium, as one of the major elements in a human body, could be engineered to avert MRSA infections, which is promising as a safe precaution of disinfection for implantable biomedical devices.

A versatile strategy to endow dental implants with long-term antibacterial ability without compromising the cytocompatibility is highly desirable to combat implant-related infection. Silver nanoparticles (Ag NPs) have been utilized as a highly effective and broad-spectrum antibacterial agent for surface modification of biomedical devices. However, the high mobility and subsequent hazardous effects of the particles on mammalian cells may limit its practical applications. Thus, Ag NPs were immobilized on the surface of sand-blasted, large grit, and acid-etched (SLA) titanium by manipulating the atomic-scale heating effect of silver plasma immersion ion implantation. The silver plasma immersion ion implantation-treated SLA surface gave rise to both good antibacterial activity and excellent compatibility with mammalian cells. The antibacterial activity rendered by the immobilized Ag NPs was assessed using Fusobacterium nucleatum and Staphylococcus aureus, commonly suspected pathogens for peri-implant disease. The immobilized Ag NPs offered a good defense against multiple cycles of bacteria attack in both F. nucleatum and S. aureus, and the mechanism was independent of silver release. F. nucleatum showed a higher susceptibility to Ag NPs than S. aureus, which might be explained by the presence of different wall structures. Moreover, the immobilized Ag NPs had no apparent toxic influence on the viability, proliferation, and differentiation of rat bone marrow mesenchymal stem cells. These results demonstrated that good bactericidal activity could be obtained with very small quantities of immobilized Ag NPs, which were not detrimental to the mammalian cells involved in the osseointegration process, and promising for titanium-based dental implants with commercial SLA surfaces.

Titanium implants possessing simultaneous osseointegration and antibacterial ability are desirable. In this work, three types of Zn/Ag micro-galvanic couples are fabricated on titanium by plasma immersion ion implantation to investigate the osseointegration and antibacterial effects as well as the involved mechanisms. The in vitro findings disclose enhanced proliferation, osteogenic differentiation, and gene expressions of the rat bone mesenchymal stem cells (rBMSCs), as well as good antibacterial ability on all three micro-galvanic couples. Excellent antimicrobial ability is also observed in vivo and the micro-CT and histological results reveal notable osseointegration in vivo despite the presence of bacteria. The Zn/Ag micro-galvanic couple formed on Zn/Ag dual-ion co-implanted titanium shows the best osseointegration as well as good antibacterial properties in vivo obtained from a rabbit tibia model. The difference among the three Zn/Ag micro-galvanic couples can be ascribed to the contact between the Ag NPs and Zn film, which affects the corrosion process. Our results indicate that the biological behavior can be controlled by the corrosion process of the Zn/Ag micro-galvanic couples., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Dental implants with proper antibacterial ability as well as ideal osseointegration are being actively pursued. The antimicrobial ability of titanium implants can be significantly enhanced via modification with silver nanoparticles (Ag NPs). However, the high mobility of Ag NPs results in their potential cytotoxicity. The silver plasma immersion ion-implantation (Ag-PIII) technique may remedy the defect. Accordingly, Ag-PIII technique was employed in this study in an attempt to reduce the mobility of Ag NPs and enhance osseointegration of sandblasted and acid-etched (SLA) dental implants. Briefly, 48 dental implants, divided equally into one control and three test groups (further treated by Ag-PIII technique with three different implantation parameters), were inserted in the mandibles of six Labrador dogs. Scanning electron microscopy, X-ray photoelectron spectroscopy, and inductively coupled plasma optical emission spectrometry were used to investigate the surface topography, chemical states, and silver release of SLA- and Ag-PIII-treated titanium dental implants. The implant stability quotient examination, Microcomputed tomography evaluation, histological observations, and histomorphometric analysis were performed to assess the osseointegration effect in vivo. The results demonstrated that normal soft tissue healing around dental implants was observed in all the groups, whereas the implant stability quotient values in Ag-PIII groups were higher than that in the SLA group. In addition, all the Ag-PIII groups, compared to the SLA-group, exhibited enhanced new bone formation, bone mineral density, and trabecular pattern. With regard to osteogenic indicators, the implants treated with Ag-PIII for 30 minutes and 60 minutes, with the diameter of the Ag NPs ranging from 5-25 nm, were better than those treated with Ag-PIII for 90 minutes, with the Ag NPs diameter out of that range. These results suggest that Ag-PIII technique can reduce the mobility of Ag NPs and enhance the osseointegration of SLA surfaces and have the potential for future use.

Prevention of periprosthetic infection (PPI) by inhibiting biofilm formation on prostheses is crucial to orthopedic surgery. In this work, silver nanoparticles (Ag NPs) are fabricated in situ and immobilized on titanium by silver plasma immersion ion implantation (PIII). The anti-biofilm activity rendered by the immobilized Ag NPs is assessed using Staphylococcus epidermidis, a biofilm producing strain, in vitro and in vivo. The immobilized Ag NPs show no apparent cytotoxicity but reduce biofilm formation in vitro by inhibiting bacteria adhesion and icaAD transcription. The immobilized Ag NPs offer a good defense against multiple cycles of bacteria attack in vitro, and the mechanism is independent of silver release. Radiographic assessment, microbiological cultures, and histopathological results demonstrate the ability of the functionalized surface against bacterial infection to reduce the risk of implant-associated PPI., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In this work, zero valent iron nanoparticles (Fezero-NPs) and iron oxide nanoparticles (Feox-NPs) were synthesized at the subsurface and surface regions of titanium oxide coatings (TOCs) by plasma immersion ion implantation. This novel Fe-NPs/TOC system showed negligible iron releasing, great electron storage capability and excellent cytocompatibility in vitro. Importantly, the system showed selective antibacterial ability which can kill Staphylococcus aureus under dark conditions but has no obvious antibacterial effect against Escherichia coli. Owing to a bipolar Schottky barrier between Fezero-NPs/TOC and Fezero-NPs/Feox-NPs, electrons could be captured by the Fezero-NPs bounded at the subsurface region of the coating. This electron storage capability of the Fe-NPs/TOC system induced extracellular electron transportation and accumulation of adequate valence-band holes (h(+)) at the external side, which caused oxidation damage to S. aureus cells in the dark. No obvious biocide effect against E. coli resulted from lack of electron transfer ability between E. coli and substrate materials. This work may open up a novel and controlled strategy to design coatings of implants with antibacterial ability and cytocompatibility for medical applications., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Zinc (Zn) and silver (Ag) are co-implanted into titanium by plasma immersion ion implantation. A Zn containing film with Ag nanoparticles (Ag NPs) possessing a wide size distribution is formed on the surface and the corrosion resistance is improved due to the micro-galvanic couples formed by the implanted Zn and Ag. Not only are the initial adhesion, spreading, proliferation and osteogenic differentiation of rBMSCs observed from the Zn/Ag implanted Ti in vitro, but also bacteria killing is achieved both in vitro and in vivo. Electrochemical polarization and ion release measurements suggest that the excellent osteogenic activity and antibacterial ability of the Zn/Ag co-implanted titanium are related to the synergistic effect resulting from the long-range interactions of the released Zn ions and short-range interactions of the embedded Ag NPs. The Zn/Ag co-implanted titanium offers both excellent osteogenic activity and antibacterial ability and has large potential in orthopedic and dental implants., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

As an implantable material, carbon-fiber-reinforced polyetheretherketone (CFRPEEK) possesses an adjustable elastic modulus similar to that of cortical bone and is a prime candidate to replace metallic surgical implants. However, the bioinertness and poor osteogenic properties of CFRPEEK limit its clinical application as orthopedic implants. In this work, titanium ions are introduced energetically into CFRPEEK by plasma immersion ion implantation (PIII). Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) reveal the formation of nanopores with the side wall and bottom embedded with ∼20 nm TiO2 nanoparticles on the CFRPEEK surface. Nanoindentation measurements confirm the stability and improved elastic resistance of the structured surfaces. In vitro cell adhesion, viability assay, and real-time PCR analyses disclose enhanced adhesion, proliferation, and osteo-differentiation of rat bone mesenchymal stem cells (bMSCs). The multilevel structures on CFRPEEK also exhibit partial antibacterial activity to Staphylococcus aureus and Escherichia coli. Our results indicate that a surface with multifunctional biological properties can be produced by multilevel surface engineering and application of CFRPEEK to orthopedic and dental implants can be broadened and expedited based on this scheme., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Titanium (Ti) and its alloys are widely used as orthopedic and dental implants. In this work, zinc (Zn) was implanted into oxalic acid etched titanium using plasma immersion ion implantation technology. Scanning electron microscopy and X-ray photoelectron spectroscopy were used to investigate the surface morphology and composition of Zn-implanted titanium. The results indicate that the depth profile of zinc in Zn-implanted titanium resembles a Gaussian distribution, and zinc exists in the form of ZnO at the surface whereas in the form of metallic Zn in the interior. The Zn-implanted titanium can significantly stimulate proliferation of osteoblastic MC3T3-E1 cells as well as initial adhesion, spreading activity, ALP activity, collagen secretion and extracellular matrix mineralization of the rat mesenchymal stem cells. The Zn-implanted titanium presents partly antibacterial effect on both Escherichia coli and Staphylococcus aureus. The ability of the Zn-implanted titanium to stimulate cell adhesion, proliferation and differentiation as well as the antibacterial effect on E. coli can be improved by increasing implantation time even to 2 h in this work, indicating that the content of zinc implanted in titanium can easily be controlled within the safe concentration using plasma immersion ion implantation technology. The Zn-implanted titanium with excellent osteogenic activity and partly antibacterial effect can serve as useful candidates for orthopedic and dental implants., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Titanium embedded with silver nanoparticles (Ag NPs) using a single step silver plasma immersion ion implantation (Ag-PIII) demonstrate micro-galvanic effects that give rise to both controlled antibacterial activity and excellent compatibility with osteoblasts. Scanning electron microscopy (SEM) shows that nanoparticles with average sizes of about 5 nm and 8 nm are formed homogeneously on the titanium surface after undergoing Ag-PIII for 0.5 h and 1 h, respectively. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) indicate that those nanoparticles are metallic silver produced on and underneath the titanium surface via a local nucleation process from the solid solution of α-Ti(Ag). The Ag-PIII samples inhibit the growth of both Staphylococcus aureus and Escherichia coli while enhancing proliferation of the osteoblast-like cell line MG63. Electrochemical polarization and Zeta potential measurements demonstrate that the low surface toxicity and good cytocompatibility are related to the micro-galvanic effect between the Ag NPs and titanium matrix. Our results show that the physico-chemical properties of the Ag NPs are important in the control of the cytotoxicity and this study opens a new window for the design of nanostructured surfaces on which the biological actions of the Ag NPs can be accurately tailored., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Periprosthetic infection is one of the trickiest clinical problems, which often leads to disastrous consequences. The emergence of tantalum and its derivatives provides novel ideas and effective methods to solve this problem and has attracted great attention. However, tantalum was reported to have different anti-infective effects in vivo and in vitro, and the inherent antibacterial capability of tantalum is still controversial, which may restrict its development as an antibacterial material to some extent. In this study, the polished tantalum was selected as the experimental object, the implant-related tibia osteomyelitis model was first established to observe whether it has an anti-infective effect in vivo compared to titanium, and the early studies found that the tantalum had a lower infectious state in the implant-related tibia osteomyelitis model in vivo than titanium. However, further in vitro studies found that the polished tantalum was not superior to the titanium against bacterial adhesion and antibacterial efficacy. In addition, we focus on the state of interaction between cells, bacteria and materials to restore the internal environment as realistically as possible. We found that the adhesion of fibroblasts to tantalum was faster and better than that of titanium. Moreover, what is more, interesting is that, in the early period, bacteria were more likely to adhere to cells that had already attached to the surface of tantalum than to the bare surface of it, and over time, the cells eventually fell off the biomaterials and took away more bacteria in tantalum, making it possible for tantalum to reduce the probability of infection in the body through this mechanism. Moreover, these results also explained the phenomenon of the "race for the surface" from a completely different perspective. This study provides a new idea for further exploring the relationship between bacteria and host tissue cells on the implant surface and a meaningful clue for optimizing the preparation of antibacterial implants in the future. [ABSTRACT FROM AUTHOR]

Bactericidal ZnO@ZnS nanorod-array facilitates the attachment and migration of human gingival fibroblasts via properly controlling the release of zinc. • A ZnO@ZnS nanorod array was designed and successfully coated on pure titanium. • The Zn release by ZnO@ZnS nanorod array was gentler than that by the ZnO one. • The ZnO@ZnS nanorods were bactericidal while promoting the function of fibroblasts. Cell-selective toxic titanium is highly desired in clinical dental practice. Herein, based on the in situ conversion of ZnO to ZnO@ZnS, nanorod-array structured coatings with a controllable release features of zinc (Zn), has been successfully fabricated by a two-step hydrothermal method to endow titanium surface with cell-selectivity, i.e. boosting the functions (attachment and migration) of human gingival fibroblasts (HGnFs) while acting against the invasion of pathogenic bacteria. The improved functions of HGnFs over the ZnO@ZnS nanorod-array were attributed to the material's optimized zinc release, which was decreased from an order of 3.5 mg L−1 to about 0.3 mg L−1 (within the first week). But more importantly, this concentration still had a high antibacterial efficacy up to 100% (against both the S. aureus and E. coli , 107 CFU mL−1). This study demonstrated that a ZnO@ZnS nanorod-array coating could be a promising strategy to endow titanium dental implants with improved soft tissue sealing and effectively reduce peri-implantitis. [ABSTRACT FROM AUTHOR]

Cell-selective biomaterials, i.e. favoring the functions of gingival cells and simultaneously reducing the adhesion of pathogenic bacteria, is highly desired in dental implants. However, due to the same mechanisms shared in attachment by mammalian and microbial cells, it is hard to increase the functions of the former while acting against the latter. Herein, a cell-selectivity was established on titanium oxide coatings by combining a plasma immersion ion implantation & deposition (PIII) and a UV pre-illumination. The titanium oxide coatings were produced on pure titanium substrates by using a plasma electrolytic oxidation technique and then doped of hafnium (Hf) by using a cathodic arc sourced PIII. The Hf-doped titanium oxide coatings (Hf-PIII groups) were capable of delaying the recombination of UV-illumination generated electron-hole pairs, which decreased the adhesion of bacterial cells at the later period (cultured for 24 h). Titanium oxide coating doped of 4.87 at.% hafnium (Hf) gained the biggest decrease (decreased 52.9% compared to its UV negative counterparts) in bacterial adhesion among the UV positive (UV+) groups. This study demonstrates that coupling Hf-doping and UV pre-illumination is promising for improving the cell-selective performance of titanium-based dental implants. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that the antibacterial action of molybdenum disulfide (MoS 2) is highly dependent on the light-activated potential of reactive oxygen species (ROS) generation; here vertically aligned molybdenum disulfide nanosheets (MoS 2 , with or without doping of iron) were coated on titanium (Ti) substrates via a one-step hydrothermal reaction, and their excellent activity against both Escherichia coli (E. coli , ATCC 25922) and Staphylococcus aureus (S. aureus , ATCC 25923) was evidenced under dark conditions. Release of MoO 4 2− and generation of MoS 2 -inspired ROS were found to be the key factors answering for the bactericidal property of the nanosheets. What's more, iron-doping in terms of FeMoO 4 could boost the antibacterial efficacy further, which stems from quick release of Fe2+ and generation of ROS by Fenton-like reactions. Accordingly, it is believed that the dark antibacterial efficacy of the vertically aligned MoS 2 nanosheets is guaranteed by uniting ion release and ROS generation. This study provides new insight into design and application of MoS 2 coatings for disinfection of biomedical devices, where light is hard to be served. [ABSTRACT FROM AUTHOR]

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-88664-z. [ABSTRACT FROM AUTHOR]