Erik N. Taylor

The relationship between the nanostructure of titanium surfaces and bacterial attachment.

Infection of an orthopedic prosthesis is undesirable and causes a decrease in the success rate of an implant. Reducing the adhesion of a broad range of bacteria could be an attractive means to decrease infection and allow for subsequent appropriate tissue integration with the biomaterial surface. In this in vitro study, nanometer sized topographical features of titanium (Ti) surfaces, which have been previously shown to enhance select protein adsorption and subsequent osteoblast (bone-forming cell) functions, were investigated as a means to also reduce bacteria adhesion. This study examined the adhesion of Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa on conventional Ti, nanorough Ti produced by electron beam evaporation, and nanotubular and nanotextured Ti produced by two different anodization processes. This study found that compared to conventional (nano-smooth) Ti, the nanorough Ti surfaces produced by electron beam evaporation decreased the adherence of all of the aforementioned bacteria the most. The conventional and nanorough Ti surfaces were found to have crystalline TiO(2) while the nanotubular and nanotextured Ti surfaces were found to be amorphous. The surface chemistries were similar for the conventional and nanorough Ti while the anodized Ti surfaces contained fluorine. Therefore, the results of this study in vitro study demonstrated that certain nanometer sized Ti topographies may be useful for reducing bacteria adhesion while promoting bone tissue formation and, thus, should be further studied for improving the efficacy of Ti-based orthopedic implants.

Reducing infections through nanotechnology and nanoparticles

The expansion of bacterial antibiotic resistance is a growing problem today. When medical devices are inserted into the body, it becomes especially difficult for the body to clear robustly adherent antibiotic-resistant biofilm infections. In addition, concerns about the spread of bacterial genetic tolerance to antibiotics, such as that found in multiple drug-resistant Staphylococcus aureus (MRSA), have significantly increased of late. As a growing direction in biomaterial design, nanomaterials (materials with at least one dimension less than 100 nm) may potentially prevent bacterial functions that lead to infections. As a first step in this direction, various nanoparticles have been explored for improving bacteria and biofilm penetration, generating reactive oxygen species, and killing bacteria, potentially providing a novel method for fighting infections that is nondrug related. This review article will first examine in detail the mechanisms and applications of some of these nanoparticles, then follow with some recent material designs utilizing nanotechnology that are centered on fighting medical device infections.

Diameter of titanium nanotubes influences anti-bacterial efficacy

Bacterial infection of in-dwelling medical devices is a growing problem that cannot be treated by traditional antibiotics due to the increasing prevalence of antimicrobial resistance and biofilm formation. Here, due to changes in surface parameters, it is proposed that bacterial adhesion can be prevented through nanosurface modifications of the medical device alone. Toward this goal, titanium was created to possess nanotubular surface topographies of highly controlled diameters of 20, 40, 60, or 80 nm, sometimes followed by heat treatment to control chemistry and crystallinity, through a novel anodization process. For the first time it was found that through the control of Ti surface parameters including chemistry, crystallinity, nanotube size, and hydrophilicity, significantly changed responses of both Staphylococcus epidermidis and Staphylococcus aureus (pathogens relevant for orthopaedic and other medical device related infections) were measured. Specifically, heat treatment of 80 nm diameter titanium tubes produced the most robust antimicrobial effect of all surface treatment parameters tested. This study provides the first step toward understanding the surface properties of nano-structured titanium that improve tissue growth (as has been previously observed with nanotubular titanium), while simultaneously reducing infection without the use of pharmaceutical drugs.

The use of superparamagnetic nanoparticles for prosthetic biofilm prevention

As with all surgical procedures, implantation comes with the added risk of infection. The goal of this in vitro study was to explore the use of superparamagnetic iron oxide nanoparticles (SPION) as a multifunctional platform to prevent biofilm formation. Results showed for the first time decreased Staphylococcus epidermidis numbers when exposed to 100 μg/ml of SPION for 12 hours and this trend continued for up to 48 hours. Prevention of colony assembly, a prerequisite to biofilm formation, was also observed at lower SPION dosages of 10 μg/ml after 12 hours. Coupled with previous studies demonstrating enhanced bone cell functions in the presence of the same concentration of SPION, the present results provided much promise for the use of SPION for numerous anti-infection orthopedic applications.

Superparamagnetic Iron Oxide Nanoparticles (SPION) for the Treatment of Antibiotic‐Resistant Biofilms

Bacterial infections caused by antibiotic-resistant strains are of deep concern due to an increasing prevalence, and are a major cause of morbidity in the United States of America. In particular, medical device failures, and thus human lives, are greatly impacted by infections, where the treatments required are further complicated by the tendency of pathogenic bacteria, such as Staphylococcus aureus, to produce antibiotic resistant biofilms. In this study, a panel of relevant antibiotics used clinically including penicillin, oxacillin, gentamicin, streptomycin, and vancomycin are tested, and although antibiotics are effective against free-floating planktonic S. aureus, either no change in biofilm function is observed, or, more frequently, biofilm function is enhanced. As an alternative, superparamagnetic iron oxide nanoparticles (SPION) are synthesized through a two-step process with dimercaptosuccinic acid as a chelator, followed by the conjugation of metals including iron, zinc, and silver; thus, the antibacterial properties of the metals are coupled to the superparamagnetic properties of SPION. SPION might be the ideal antibacterial treatment, with a superior ability to decrease multiple bacterial functions, target infections in a magnetic field, and had activity better than antibiotics or metal salts alone, as is required for the treatment of medical device infections for which no treatment exists today.

Effects of different sterilization techniques and varying anodized TiO2 nanotube dimensions on bacteria growth

Infection of titanium (Ti)-based orthopedic implants is a growing problem due to the ability of bacteria to develop a resistance to todays antibiotics. As an attempt to develop a new strategy to combat bacteria functions, Ti was anodized in the present study to possess different diameters of nanotubes. It is reported here for the first time that Ti anodized to possess 20 nm tubes then followed by heat treatment to remove fluorine deposited from the HF anodization electrolyte solution significantly reduced both S. aureus and S. epidermidis growth compared to unanodized Ti controls. It was further found that the sterilization method used for both anodized nanotubular Ti and conventional Ti played an important role in the degree of bacteria growth on these substrates. Overall, UV light and ethanol sterilized samples decreased bacteria growth, while autoclaving resulted in the highest amount of bacteria growth. In summary, this study indicated that through a simple and inexpensive process, Ti can be anodized to possess 20 nm tubes that no matter how sterilized (UV light, ethanol soaking, or autoclaving) reduces bacteria growth and, thus, shows great promise as an antibacterial implant material.

Fructose-enhanced reduction of bacterial growth on nanorough surfaces

In this study, we present for the first time that the presence of fructose metabolites on the nanorough polyvinyl chloride surfaces decreases the number of planktonic bacteria in the solution and biofilm formation on the surface after 24 hours.

Short communication: Carboxylate functionalized superparamagnetic iron oxide nanoparticles (SPION) for the reduction of S. aureus growth post biofilm formation.

Biofilms formed by antibiotic resistant Staphylococcus aureus (S. aureus) continue to be a problem for medical devices. Antibiotic resistant bacteria (such as S. aureus) often complicate the treatment and healing of the patient, yet, medical devices are needed to heal such patients. Therefore, methods to treat these Biofilms once formed on medical devices are badly needed. Due to their small size and magnetic properties, superparamagnetic iron oxide nanoparticles (SPION) may be one possible material to penetrate Biofilms and kill or slow the growth of bacteria. In this study, SPION were functionalized with amine, carboxylate, and isocyanate functional groups to further improve their efficacy to disrupt the growth of S. aureus Biofilms. Without the use of antibiotics, results showed that SPION functionalized with carboxylate groups (followed by isocyanate then amine functional groups then unfunctionalized SPION) significantly disrupted Biofilms and retarded the growth of S. aureus compared to untreated Biofilms (by over 35% after 24 hours).

Iron Oxide Nanoparticles: Novel Drug Delivery Materials for Treating Bone Diseases

Magnetic nanoparticles have been used extensively as drug delivery materials in recent years [1,2]. The present research goal is to treat bone diseases (such as osteoporosis and infection) by using surface modified magnetic nanoparticles. Magnetite (Fe3O4) and maghemite (Fe2O3) were synthesized and coated with calcium phosphate (CaP). The resulting nanoparticles were treated hydrothermally to change the crystalline properties of CaP. Nanoparticles were characterized via transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). TEM was also used to study the uptake of nanoparticles into osteoblasts (OB) and bacteria. OB proliferation experiments were conducted after 1, 3 and 5 days in the presence of the various iron oxide nanoparticles alone and CaP coated iron oxide magnetic nanoparticles. OB proliferation experiments were also conducted after 1, 3 and 5 days in the presence of various concentrations of CaP coated nanoparticles to examine a possible concentration dependent trend on OB density. Staph epidermidis were incubated with different doses of Fe3O4 to determine the effect of these nanoparticles on bacteria activity. Results of this in vitro study demonstrated greater OB functions and inhibited bacteria functions in the presence of select magnetic nanoparticles. In summary, the results of this study showed that magnetic nanoparticles should be further studied for various orthopedic applications.

Antimicrobial performance of mesoporous titania thin films: role of pore size, hydrophobicity, and antibiotic release.

Implant-associated infections are undesirable complications that might arise after implant surgery. If the infection is not prevented, it can lead to tremendous cost, trauma, and even life threatening conditions for the patient. Development of an implant coating loaded with antimicrobial substances would be an effective way to improve the success rate of implants. In this study, the in vitro efficacy of mesoporous titania thin films used as a novel antimicrobial release coating was evaluated. Mesoporous titania thin films with pore diameters of 4, 6, and 7 nm were synthesized using the evaporation-induced self-assembly method. The films were characterized and loaded with antimicrobial agents, including vancomycin, gentamicin, and daptomycin. Staphylococcus aureus and Pseudomonas aeruginosa were used to evaluate their effectiveness toward inhibiting bacterial colonization. Drug loading and delivery were studied using a quartz crystal microbalance with dissipation monitoring, which showed successful loading and release of the antibiotics from the surfaces. Results from counting bacterial colony-forming units showed reduced bacterial adhesion on the drug-loaded films. Interestingly, the presence of the pores alone had a desired effect on bacterial colonization, which can be attributed to the documented nanotopographical effect. In summary, this study provides significant promise for the use of mesoporous titania thin films for reducing implant infections.