Mesoporous TiO2 implants for loading high dosage of antibacterial agent
Graphical abstract
Introduction
Titanium metal and its oxides are widely used as dental and orthopedic implants due to their good biocompatibility and stability. There has been a great deal of research performed regarding surface modifications of these implants to generate hydrophilic surfaces with improved osseointegration [1], [2], [3], [4]. The 10-year implant survival and success rates of a surface modified implant have been reported to be more than 95% [5], however, there are still problems such as peri-implantitis. The cause of peri-implantitis includes several factors, however, microorganisms play a major role in causing peri-implantitis [6], [7].
The use of mesoporous titania structures in dental and orthopedic implants has been widely investigated. These structures have a large surface area which presents a platform for controlled drug delivery in a sustainable fashion [8], [9]. Additionally, TiO2 nanotube structures for drug delivery have been investigated [10]. In vivo biomechanical stability of mesoporous implants has also been evaluated [11]. In previous studies, evaporation-induced self-assembly [8], [11], [12] and suspended colloid particle methods were used [13] to make mesoporous TiO2 thin films on implant substrates. Additionally, mesoporous Ag-TiO2 films have been made by reducing a silver precursor followed by oxidation with TiCl4 solution [14], [15].
In this study, mesoporous thin films were fabricated on anodized Ti substrates using a paste comprised of ∼20 nm of pre-synthesized TiO2 nanoparticles. The paste method has been widely used in the field of solar cells [16]. We applied this method to the generation of biomaterials. The TiO2 paste method has some advantages over previously studied methods. This method allows for the thickness of the mesoporous thin films to be easily controlled. Additionally, the size and shape of these nanoparticles could be controlled by selecting the appropriate pre-synthesized TiO2 nanoparticles with desired properties. Additionally, a variety of organic components (ethyl cellulose, lauric acid, and viscous terpineol) could be added to make firm and stable mesoporous thin films. Because this technique uses pre-synthesized TiO2 nanoparticles, not only can the thickness be controlled, but also the amount of loaded drugs could be controlled. Oxidation of TiCl4 [14] is a method to form mechanically stable mesoporous films, however, this method does not allow for the control of film thickness or amount of loaded drug.
The high surface area of these films allowed for loading high doses of four antibacterial agents (silver nanoparticles, cephalothin, minocycline, and amoxicillin). Silver nanoparticles were synthesized through adsorption of AgNO3 and reduction via UV irradiation while the other drugs were loaded into the thin films by immersing the thin films in aqueous solutions of each drug, respectively. Antibacterial activities of the drug-loaded films were evaluated using five different bacterial species (Staphylococcus aureus, Pseudomonas aeruginosa, Aggregatibacter actinomycetemcomitans Y4, Prevotella intermedia, Porphyromonas gingivalis) by the antibacterial inhibition zone assay. Additionally, quantitative analysis of antibacterial effectiveness and bacterial viabilities was investigated by time-kill experiments.
Section snippets
Preparation of mesoporous TiO2 thin films
Circular titanium substrates (diameter: 12 mm, thickness: 1 mm) were supplied by Biotem Co., Ltd. (Busan, Korea). Ti disks were cleaned twice and sonicated for 15 min with hexane, acetone, ethanol, and distilled water sequentially. Anodic oxidation was performed as previously reported [17]. Using a titanium cathode and anode, Ti disks were anodized at 150 V for 2 min in 2.0 M H2SO4 aqueous solution at 0 °C in a glass chamber. A titanium oxide nanoparticle paste (Ti-20, ENB, Korea) was diluted five
Mesoporous TiO2 thin film preparation and surface characterization
Mesoporous thin films on Ti metal disks were fabricated according to the following procedure (Fig. 1). First, the Ti metal disks were anodized in 2.0 M H2SO4 aqueous solution with 150 V of applied voltage for 2 min. The anodized surface morphology is shown in Fig. 1(a). The formation of an anodized oxide surface not only increases the surface area and roughness, but also provides a good surface for adhesion to TiO2 nanoparticles via the sintering process. The latter is the most important reason to
Conclusion
We successfully fabricated TiO2 mesoporous thin films on Ti substrates using anodization and sintering of a paste of TiO2 nanoparticles. Due to the highly increased surface area, large quantities of antibacterial agents could be loaded. Four kinds of agents including silver nanoparticles and various antibiotics were loaded and each one showed varying antibacterial activity against five different bacterial strains. By combining two kinds of antibacterial agents, we fabricated thin films which
Acknowledgments
The authors would like to thank Biotem Co., Ltd. (Busan, Korea) for supplying titanium disks. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (No. NRF-2012R1A5A2051388, NRF-2012-0008610, and NRF-2010-0019346).
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2021, Bioactive MaterialsCitation Excerpt :Drug-loaded surfaces. The drugs include conventional antibiotics such as amoxicillin [59], vancomycin [60–62], gentamicin [63], tetracycline [64], minocycline [59,65], cephalotin [66] and chlorhexidine [59,67]. Antibacterial peptide surfaces (AMPs).