Zhifen Wu

Antibacterial Coatings on Titanium Implants

Titanium and titanium alloys are key biomedical materials because of their good biocompatibility and mechanical properties. Nevertheless, infection on and around titanium implants still remains a problem which is usually difficult to treat and may lead to eventual implant removal. As a result, preventive measures are necessary to mitigate implant-frelated infection. One important strategy is to render the implant surface antibacterial by impeding the formation of a biofilm. A number of approaches have been proposed for this purpose and they are reviewed in this article.

Antibacterial nano-structured titania coating incorporated with silver nanoparticles.

Titanium (Ti) implants are widely used clinically but post-operation infection remains one of the most common and serious complications. A surface boasting long-term antibacterial ability is highly desirable in order to prevent implant associated infection. In this study, titania nanotubes (TiO(2)-NTs) incorporated with silver (Ag) nanoparticles are fabricated on Ti implants to achieve this purpose. The Ag nanoparticles adhere tightly to the wall of the TiO(2)-NTs prepared by immersion in a silver nitrate solution followed by ultraviolet light radiation. The amount of Ag introduced to the NTs can be varied by changing processing parameters such as the AgNO(3) concentration and immersion time. The TiO(2)-NTs loaded with Ag nanoparticles (NT-Ag) can kill all the planktonic bacteria in the suspension during the first several days, and the ability of the NT-Ag to prevent bacterial adhesion is maintained without obvious decline for 30 days, which are normally long enough to prevent post-operation infection in the early and intermediate stages and perhaps even late infection around the implant. Although the NT-Ag structure shows some cytotoxicity, it can be reduced by controlling the Ag release rate. The NT-Ag materials are also expected to possess satisfactory osteoconductivity in addition to the good biological performance expected of TiO(2)-NTs. This controllable NT-Ag structure which provides relatively long-term antibacterial ability and good tissue integration has promising applications in orthopedics, dentistry, and other biomedical devices.

The influence of hierarchical hybrid micro/nano-textured titanium surface with titania nanotubes on osteoblast functions

Hierarchical hybrid micro/nano-textured titanium surface topographies with titania nanotubes were produced by simple acid etching followed by anodization to mimic the hierarchical structure of bone tissues. Primary rat osteoblasts were used to evaluate the bioactivity. The microtopography formed by acid etching of titanium induced inconsistent osteoblast functions with initial cell adhesion and osteogenesis-related gene expression being dramatically enhanced while other cell behaviors such as proliferation, intracellular total protein synthesis and alkaline phosphatase activity, collagen secretion, and extracellular matrix mineralization being depressed. In comparison, addition of nanotubes to the microtopography led to enhancement of multiple osteoblast functions. Nearly all the cell functions investigated in this study were retained or promoted. Compared to a microtopography, the enhancement of multiple cell functions observed from the hierarchical micro/nano-textured surfaces is expected to lead to faster bone maturation around the titanium implants without compromising the bone mass. In addition, the hierarchical micro/nano-textured surfaces still retain the mechanical interlocking ability of the microtopography thereby boding well for osseointegration. Our study reveals a synergistic role played by the micro and nanotopographies in osteoblast functions and provides insight to the design of better biomedical implant surfaces.

Effects of micropitted/nanotubular titania topographies on bone mesenchymal stem cell osteogenic differentiation

Micro/nanotopographical modification of biomaterials constitutes a promising approach to direct stem cell osteogenic differentiation to promote osseointegration. In this work, titania nanotubes (NTs) 25 and 80 nm in size with the acid-etched Ti topography (AcidTi) and hierarchical hybrid micropitted/nanotubular topographies (Micro/5VNT and Micro/20VNT) are produced to mimic the structure of the natural bone extracellular matrix (ECM). The effects on bone mesenchymal stem cell (MSC) osteogenic differentiation are studied systematically by various microscopic and biological characterization techniques. Cell adhesion is assayed by nucleus fluorescence staining and cell proliferation is studied by CCK-8 assay and flow cytometry. Osteogenic differentiation is assayed by alkaline phosphatase (ALP) expression, collagen secretion, matrix mineralization, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis on the osteogenesis related gene expression. All the topographies are observed to induce MSC osteogenic differentiation in the absence of osteogenic supplements. The nanotube surfaces significantly promote cell attachment and spread, collagen secretion and ECM mineralization, as well as osteogenesis-related gene expression. Among them, Micro/20VNT shows the best ability to simultaneously promote MSC proliferation and osteogenic differentiation. Our results unambiguously demonstrate their excellent ability to support MSC proliferation and induce MSC osteogenic differentiation, especially those with the micropitted topography.

In vitro cellular responses to scaffolds containing two microencapulated growth factors

Growth factors play an important role in the complex cascade of tissue events in periodontal regeneration, although optimal methods of delivery remain to be identified. We hypothesize that multiple delivery of growth factors, particularly via a microparticle-containing scaffold, will enhance cellular events leading to periodontal regeneration. In this study, cellular responses of periodontal ligament fibroblasts (PDLFs) in scaffolds containing microparticles (MPs) loaded with either bone morphogenetic protein (BMP)-2, insulin-like growth factor (IGF)-1, or a mixture of both MPs were evaluated, and the dual-MP-containing scaffold exhibited the release of different proteins in a sustained and independent fashion. When PDLF-seeded scaffolds were cultured in a flow perfusion bioreactor, cell metabolism and proliferation of PDLFs were significantly increased within 3 days in all IGF-1-containing scaffolds compared with those in groups lacking IGF-1 and particulate delivery enhanced these effects between 3 and 7 days. The dual-MP-containing group showed the most positive results. Both the BMP-2-in-MP and IGF-1-in-MP groups showed greater effects of alkaline phosphatase activity, more osteocalcin and osteopontin production, and more calcium deposition compared with matched GF-adsorbed groups. All osteoblastic markers were at their highest in the dual-MP-containing group at all detected time points. The combined results suggest that our dual-MP-containing scaffold can be used as a cell vehicle to positively affect cell behavior, thus exhibiting the potential to be a candidate scaffold for future periodontal tissue engineering.

The role of sterilization in the cytocompatibility of titania nanotubes.

Titiania nanotubes have large potential in medical implant applications but their tissue compatibility is still controversial. Since the sterilization methods may impact the biocompatibility of titania nanotubes and be the source of the controversy, we investigate the influence of three commonly used sterilization methods, autoclaving, ultraviolet irradiation and ethanol immersion, on the cytocompatibility of titania nanotubes. Two titania nanostructures, namely nanonets with an average pore diameter of 25 nm and nanotubes with an average diameter of 80 nm, are used in this study. The results show that the sterilization methods significantly affect the cytocompatibility of these titania surfaces. UV and ethanol sterilization give rise to a higher surface free energy inducing higher initial cell adhesion and proliferation compared to autoclaving, whereas UV irradiation produces the best cell functions including adhesion, proliferation, as well as differentiation represented by related gene expressions. The cytocompatibility results obtained from the nanoscale surfaces are compared to those acquired from the polished surface demonstrating the significant effects. Our results suggest that the sterilization process plays an important role in the observed cytocompatibility of titania nanotubes and may be the reason for the controversial results so far. UV sterilization is found to be the best method from the viewpoint of surface contamination elimination.

Mechanism of cell repellence on quasi-aligned nanowire arrays on Ti alloy

Cell-repelling structures are often required in biosensors, bioelectronics, and drug delivery systems, but the search for satisfactory cell-repelling structures with good biocompatibility and long-term stability is challenging. In this work, two types of quasi-aligned nanowire arrays (QANWA) with different surface chemistry but similar surface topography, namely titanium carbide-carbon core-shell (TiC/C) and titania (TiO(2)), are fabricated on Ti6Al4V. Both QANWAs inhibit cell adhesion consequently leading to cell apoptosis possibly due to disruption in the adhesion assembly. Other cell functions such as proliferation and differentiation as monitored by extracellular matrix secretion and mineralization are also substantially depressed. The cell-repelling property is related to the nanostructure but independent of the surface chemistry and surface wettability. It is also not related to protein adsorption which is in fact slightly enhanced on the nanowire arrays. The QANWAs can be modified to have a larger loading capacity thereby enhancing the controlled release kinetics in drug delivery applications and to resist protein adsorption resulting in better biosensor performance. This concept which can be readily extended to other types of QANWAs and biomaterials has broad clinical potential.

Suppressed primary osteoblast functions on nanoporous titania surface

Titiania nanotubes have large potential in medical implant applications but their tissue compatibility is still controversial. Considering that the biological behavior of primary osteoblasts is closer to the in vivo situation than other common cell lines, we investigate the response of primary osteoblasts on anodized nanotextured titania surfaces. Two nanotextured surface morphologies, namely the 5 V anodized surface with a pore diameter of 25 nm and the 20 V anodized surface with a tube diameter of 80 nm are chosen for this study. Initial cell adhesion is not obviously affected by the anodized surfaces. With the exception of slightly higher intracellular alkaline phosphatase activity and more extracellular matrix deposition, cell growth, and cell differentiation represented by the expressions of osteogenesis-related genes are impaired on both anodized surfaces. This may be attributed to the compromised focal contact formation on the anodized surfaces. The difference in the phenotypes of the primary osteoblasts and the osteoblastic cell lines may partly account for the controversy in osteoblast cytocompatibility on titania nanotubes.

Low-magnitude mechanical vibration may be applied clinically to promote dental implant osseointegration

Dental implants have been widely used clinically, but there still remain great challenges for a stronger bone-implant bonding and a shorter rehabilitation time. Osseointegration of dental implant is crucial for their long term clinical success. Recently, there are abundant evidences showing that low mechanical stimuli can strengthen bones, inhibit osteopenia and enhance bone healing. It has been showed that low-amplitude mechanical stimuli have favorable influence on osteoblasts and their precursors. Preliminary studies indicated that low-magnitude mechanical stimuli may assist in implant osseointegration. So collectively we hypothesize that low-magnitude mechanical vibration may be applied clinically to strengthen and accelerate osseointegration of dental implants.