The effects of titania nanotubes with embedded silver oxide nanoparticles on bacteria and osteoblasts
Introduction
Biomaterial-related infection is one of the most serious post-operative complications of medical implants resulting in patient suffering, financial burden, and even fatalities [1]. Infection may result from incomplete pre-operation disinfection, non-standard protocols during surgical procedure, or transfer of bacteria from infected, adjacent tissues and hematogenous sources to the implant surface after surgery. Despite strict sterilization and aseptic procedures, bacteria contamination cannot be completely avoided. After the bacteria reach the implant surface, they will aggregate in the extracellular viscous polysaccharide secreted by themselves to form a biofilm. The biofilm makes the bacteria highly resistant to the host defense and antibacterial agents thereby leading to persistent and chronic infections [2]. An effective measure to combat the infection is to endow the implants with antibacterial ability to inhibit initial bacterial adherence and subsequent formation of the biofilm [3]. In particular, many implants are susceptible to bacterial invasion throughout the lifetime and so long-term antibacterial ability is desirable. At the same time, the process to endow biomaterials with the desirable antibacterial ability should not compromise the cytocompatibility.
Topographical modification on the nanoscale can effectively improve the biological performance of biomaterials [4]. Recently, highly ordered and vertically oriented TiO2 nanotube (NT) arrays fabricated by electrochemical anodization of titanium (Ti) and its alloys have captured much interest as biomedical coatings, and their diameter and length can be precisely controlled by varying the anodic parameters [5], [6]. Owing to their self-organizing nature, even a surface with a complex shape can be coated relatively easily [6]. Many in vitro and in vivo studies have demonstrated that these TiO2 NT arrays have excellent biological performance. For instance, the TiO2 NT arrays have beneficial effects on the functions of many kinds of cells such as endothelial cells [7], [8], [9], vascular smooth muscle cells [8], human mesenchymal stem cells [9], [10], [11], [12] and osteoblasts [13], [14], [15]. Particularly, their effectiveness in promoting osseointegration in vivo is quite encouraging in orthopedic and orthodontic applications [16].
TiO2 NT arrays have inadequate antibacterial ability and efforts have been made to improve their antibacterial properties. Considering that TiO2 NT arrays are potential drug carriers, antibacterial agents can be loaded. Popat et al. [17] have loaded antibiotics into TiO2 NTs and mitigated adhesion of Staphylococcus epidermis is observed. However, release of antibiotics from the NTs is too fast to maintain the long-term antibacterial ability and the use of antibiotics increases the resistance to antibiotics. Antimicrobial peptides are suggested to be a safer choice because of the smaller possibility of developing resistant strains, but the release rate after introduction to NTs is still too fast to sustain the long term antibacterial activity and in vivo decomposition of the antimicrobial peptides is another drawback [18]. In comparison, inorganic silver (Ag) may be a better choice because of its broad-spectrum antibacterial property, low cytotoxicity, good stability, and small possibility to develop resistant strains [3], [19]. Ag nanoparticles (NPs) or salts are currently used in a variety of medical materials and devices to prevent infection, for instance, wound dressing [20], burn ointments [21], catheters [22], [23], vascular grafts [24], and bone fixation devices [25], [26]. We have previously incorporated Ag NPs into TiO2 NT arrays (denoted as NT-Ag arrays) by a simple photo-reduction method and the Ag NPs are attached to the NT sidewalls [27]. Long-term antibacterial ability has been observed from the NT-Ag arrays, but unfortunately, cytotoxicity is observed due to fast release of silver ions (Ag+). A more cytocompatible Ag incorporated TiO2 NT array structure with controlled Ag+ release is therefore highly required.
Instead of loading Ag into the as-formed TiO2 NT arrays, a strategy to deposit a TiAg coating on Ti followed by anodization is utilized to fabricate the Ag loaded TiO2 NT arrays in this work. This process produces Ag2O NP embedded TiO2 NT arrays (NT-Ag2O arrays) with a unique structure of crystallized Ag2O NPs embedded in amorphous titania nanotube wall and owing to the barrier effect rendered by the titania, the NT-Ag2O arrays show slower Ag+ release.
Section snippets
Preparation of TiAg coatings by magnetron sputtering
Pure Ti rods were cut into thin sheets (Φ14 mm × 2 mm) and used as substrates. The specimens were polished to a mirror finish followed by sequentially ultrasonic cleaning in acetone, ethanol, and deionized water for 5 min, respectively, and drying in air before introducing into the deposition chamber. The TiAg coatings were deposited on Ti by pulsed DC magnetron sputtering with TiAg targets at ambient temperature. The Ag concentrations in the coatings were varied by using five TiAg targets with
Sample characterization
The surface and cross-sectional morphology of the as-deposited pure Ti and TiAg coatings with different Ag concentrations are shown in Fig. 1. The pure Ti coating (Fig. 1a) exhibits a densely populated and vertically aligned columnar structure with an average column diameter of about 200 nm. Regarding the TiAg coatings, as the Ag content is increased (Figs. 1b–f), the columnar structure gradually transforms to a layered structure and bright spots arising from Ag NPs as verified by EDS become
Discussion
The proper approach that can endow biomaterials with long-term antibacterial ability while not impairing the biological properties of biomaterials is being actively pursued [29]. We have fabricated NT-Ag arrays on Ti with long-term antibacterial activity but cytotoxicity is also observed due to excessive release of Ag+ [27]. In this work, we report the NT-Ag2O array structure with crystallized Ag2O NPs embedded in amorphous TiO2 nanotube wall. The materials show slower Ag+ release because the
Conclusion
The NT-Ag2O arrays are produced by magnetron sputtering of TiAg coatings and anodization. The materials are composed of crystallized Ag2O NPs embedded in the amorphous TiO2 nanotube wall and controlled Ag+ release at a low dose is observed. The Ag contents in the NT-Ag2O arrays can be changed by varying the deposition parameters of the TiAg coatings. After immersion for up to 28 days, the NT-Ag2O arrays show antibacterial rates higher than 97%, indicating long lasting and effective
Acknowledgments
This work is jointly supported by the National Natural Science Foundation of China (51171125, 31300808, 31200716), Specialized Research Fund for the Doctoral Program of Higher Education of China (20131402120006), Natural Science Foundation of Shanxi Province (2013021011-1, 2012021021-7), School Foundation of Taiyuan University of Technology (2013T013), City University of Hong Kong Applied Research Grants (ARG) Nos. 9667066 and 9667069, as well as Hong Kong Research Grants Council (RGC) General
References (53)
- et al.
The effect of TiO2 nanotubes on endothelial function and smooth muscle proliferation
Biomaterials
(2009) - et al.
Effects of micropitted/nanotubular titania topographies on bone mesenchymal stem cell osteogenic differentiation
Biomaterials
(2012) - et al.
The use of carbon nanotubes to induce osteogenic differentiation of human adipose-derived MSCs in vitro and ectopic bone formation in vivo
Biomaterials
(2012) - et al.
Influence of engineered titania nanotubular surfaces on bone cells
Biomaterials
(2007) - et al.
Improved bone-forming functionality on diameter-controlled TiO2 nanotube surface
Acta Biomater
(2009) - et al.
TiO2 nanotubes for bone regeneration
Trends Biotechnol
(2012) - et al.
Effects of TiO2 nanotubes with different diameters on gene expression and osseointegration of implants in minipigs
Biomaterials
(2011) - et al.
Decreased Staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes
Biomaterials
(2007) A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver
Burns
(2000)- et al.
Effect of silver-coated urinary catheters: efficacy, cost-effectiveness, and antimicrobial resistance
Am J Infect Control
(2004)
Use of an oxonol dye in combination with confocal laser scanning microscopy to monitor damage to Staphylococcus aureus cells during colonisation of silver-coated vascular grafts
Int J Antimicrob Agents
Silver coated materials for external fixation devices: in vitro biocompatibility and genotoxicity
Biomaterials
Antibacterial nano-structured titania coating incorporated with silver nanoparticles
Biomaterials
Balancing osteoblast functions and bacterial adhesion on functionalized titanium surfaces
Biomaterials
Fabrication of self-organized TiO2 nanotubes from columnar titanium thin films sputtered on semiconductor surfaces
Electrochem Commun
Magnetron sputtering of alloy and alloy-based films
Thin Solid Films
An in vitro assessment of the antibacterial properties and cytotoxicity of nanoparticulate silver bone cement
Biomaterials
Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria
J Colloid Interface Sci
Osteogenic activity and antibacterial effects on titanium surfaces modified with Zn-incorporated nanotube arrays
Biomaterials
Uptake and intracellular distribution of silver nanoparticles in human mesenchymal stem cells
Acta Biomater
Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism
Toxicol In Vitro
Nanosilver: a nanoproduct in medical application
Toxicol Lett
The osteogenic activity of strontium loaded titania nanotube arrays on titanium substrates
Biomaterials
Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment
Dev Cell
Cell–cell communication in the osteoblast/osteocyte lineage
Arch Biochem Biophys
Recent advances in magnetron sputtering
Surf Coat Tech
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