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Developing synergistic strategies by combining bactericidal nanotopography with biophysical stimulation to combat biomaterials associated infections


   School of Oral & Dental Science


About the Project

Biomaterials such as titanium metal and its alloys have been widely used in permanent implants and medical devices to restore or support human functions. However, biomaterial-associated infections (BAIs) are becoming an increasing problem where antibiotic therapies are often proven to be ineffective. A recent WHO report (2019) on global antimicrobial resistance (AMR) highlights not only the growing issue of resistance, identifying it as one of the greatest threats we face as a global community, but also the lack of new effective options to tackle AMR bacterial infections.

Nanotechnology has been emerging as a powerful tool to combat AMR BAIs. Biophysical stimulation could potentially offer another physical cue to modulate bacteria and host cells. The design of novel strategies to effectively prevent BAIs requires a better understanding of how to win a competition between host tissue cell integration and bacterial colonisation at the biomaterial surfaces. Protruding nanotopographies e.g., nanopillars like those found on insect wings have shown unique mechano-bactericidal properties [1]. We have developed a range of biomimetic bactericidal nanostructures on titanium implant materials and investigated their multifaceted bactericidal mechanisms [2-7]. Recent studies have shown that application of low electric currents on nanostructured surfaces can inactivate bacteria with high efficiency [8]. Electrical stimulation can also enhance cell functions for both soft and hard tissues [9].

Aims and objectives

The aim of this project is to investigate synergistic effects of nanotopography combined with electrical stimulation on the responses of bacteria and cells, and to develop new strategies to combat BAIs while enhancing the cell functions of host tissues.

The objectives include:

  • Generation and characterisation of bactericidal nanotopographies
  • Investigation of bacterial response to nanotopograhies under biophysical stimulation
  • Investigation of cellular response to nanotopographies under biophysical stimulation
  • Investigation of synergistic cell-instructive mechanisms

Methodology

Firstly, bactericidal nanotopographies will be created on both flat and 3D printed titanium surfaces using hydrothermal etching and annealing. Nanostructured surfaces with tuneable feature sizes will be produced. A range of analytical and microscopic techniques (XPS, XRD, SEM, TEM, AFM) will be used to characterise the nanostructured surfaces. Other physical properties e.g., wettability and conductivity will also be characterised.

Secondly, bactericidal properties of the nanostructured surfaces under electrical stimulation will be assessed by measurement of bacterial metabolic activity and viability using BacTiter-Glo Viability and Live/Dead assay for end-point analysis. Clinical pathogens associated with oral and orthopaedic infections will be investigated, including Gram-positive Streptococcus mutans, Staphylococcus aureus and Staphylococcus epidermidis, and Gram-negative Escherichia coli and Pseudomonas aeruginosa. The effects of electric current and surface nanotopography on the bactericidal performance will be investigated.

Finally, cellular response of the nanostructured surfaces under electrical stimulation will be evaluated using epithelial or mesenchymal stem cells (MSC). Optimal bactericidal nanotopographies under electric currents with cytocompatibility and cell functions will be identified. The synergistic mechanisms of nanotopography under electrical stimulation for enhanced bactericidal and cellular performance will be elucidated.

Apply for this project

This project will be based in Bristol Dental School.

Please contact for further details on how to apply.

Apply now!


References

1. Elena P. Ivanova, et al. Natural bactericidal surfaces: mechanical rupture of Pseudomondas aeruginosa cells by cicada wings. Small 8(2012) 2489–2494
2. Ting Diu, et al., Cicada-inspired cell-instructive nanopatterned arrays, Scientific Reports 4 (2014) 7122.
3. Penelope M. Tsimbouri, et al. Osteogenic and bactericidal surfaces from hydrothermal titania nanowires on titanium substrates, Scientific Reports, 6 (2016) 36857
4. Abinash Tripathy, et al. Natural and bioinspired nanostructured bactericidal surfaces, Advances in Colloid and Interface Science 248 (2017) 85–104
5. Gavin Hazell, et al. Bioinspired bactericidal surfaces with polymer nanocone arrays, Journal of Colloid & Interface Science 528 (2018) 388-398
6. Joshua Jenkins, et al. Antibacterial effects of nanopillar surfaces are mediated by cell impedance, penetration and induction of oxidative stress, Nature Communications 11 (2020) 1626.
7. Mohd I. Ishak, et al. Insights into complex nanopillar-bacteria interactions: Roles of nanotopography and bacterial surface proteins, Journal of Colloid and Interface Science 604 (2021) 91–103
8. Chong Liu, et al. Conducting Nanosponge Electroporation for Affordable and High-Efficiency Disinfection of Bacteria and Viruses in Water, Nano Letters 13 (2013) 4288−4293
9. Shi-Ting Chen, et al. Microscopic Volta potential difference on metallic surface promotes the osteogenic differentiation and proliferation of human mesenchymal stem cells, Materials Science & Engineering C 128 (2021) 112325

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