Implanted medical devices like hip replacements and dentures aren't supposed to come with a side of infections. Yet, many patients leave the hospital with both a new implant and a bacterial or fungal infection brewing on the surface of their new device. In fact, up to 70 percent of all hospital-acquired infections are caused by bacterial or fungal cells that fuse together and create slimy biofilms on the devices (1). These common infections require antibiotics that contribute to widespread resistance, or they include microbial strains that are already resistant to antibiotic treatment and thus are challenging to treat.

Over a decade ago, Elena Ivanova, a nanobiotechnologist at the Royal Melbourne Institute of Technology (RMIT), began looking for nature-inspired solutions to treat device-associated infections. In a recent paper, Ivanova's team created the first insect-wing-inspired titanium surface designed to wipe out fungus. They found that their micro-pillared design killed 100 percent of multiple Candida fungal species via two separate mechanisms (2). Their new titanium surface — a biocompatible material used in most medical devices — adds to a growing list of biomaterials that could be used in medical devices to prevent harmful biofilm growth.

"It is extremely important we invest in and develop this technology because it can globally contribute to the effort for infection prevention and control, and therefore contribute to stop what we call now the silent pandemic of the emergence of antimicrobial-resistant disease,” said Martyna Michalska, a nanobiotechnologist at University College London who was not involved in the study."

It is extremely important we invest in and develop this technology because it can globally contribute to the effort for infection prevention and control, and therefore contribute to stop what we call now the silent pandemic of the emergence of antimicrobial-resistant disease. 
- Martyna Michalska, University College London

Ivanova first began looking for nature-inspired solutions to combat bacterial infections on devices. “Bacteria are the oldest living creatures in our planet,” she said. “They can adapt, and they can colonize practically every surface. But in nature, you can find surfaces that are free from bacteria.” 

In 2012, her team discovered that the wings of the cicada insect are chock full of nanopillars that kill bacteria on contact (3). Shortly after, in 2013, her team engineered the first analogue on black silicon inspired by the nanopillars on dragonfly wings (4). Her team’s continued work showed that insect-inspired antibacterial nanomaterials offer a drug-free way to kill bacteria.

In the new work, Ivanova’s team shifted their aim to thwart fungal biofilms. They targeted Candida species known to lead to potentially fatal and resistant infections worldwide. “It was not clear how these different types of microorganisms will respond on nanostructured surfaces,” said Ivanova. 

They found that their dragonfly-inspired titanium surface killed 50 percent of the Candida cells immediately with its micropillars by stretching their cell walls until they ruptured. Ivanova was excited to discover that the other 50 percent of Candida cells also soon died because the surface injured them and caused such severe metabolic stress that it triggered apoptosis. “The most important thing is that the anti[fungal] resistance will not be developed because cells simply don't have time. If they are not surviving, they can't adapt,”  said Ivanova. “This is the first report on Candida that the nanostructure surface may trigger apoptosis cell death of injured cells, not just [cells] killed on the surfaces.” 

Michalska noted that it’s still unclear whether the same surface pattern used in the present study could generalize to kill other types of Candida species not tested. “The problem is that even within Candida species … those biofilms look very, very different for each one of them,” she said.

At the same time, Michalska added that the ideal goal would be to develop a single surface that could kill many types of microbial infections, especially since device-associated infections often display mixed biofilms with fungal and bacterial species. “These kinds of mixed biofilms are extremely difficult to treat,” said Michalska.  

Ivanova agreed that future research should investigate whether a single nanostructured pattern could prevent all types of biofilms from growing on implanted devices. “That is the million-dollar question,” she said. 

References

1. Bryers, J. D. Medical biofilms. Biotechnol Bioeng  100, 1–18 (2008).
2. Le, P. H. et al. Apoptosis of Multi-Drug Resistant Candida Species on Microstructured Titanium Surfaces. Adv Mater Int 10, 2300314 (2023).
3. Ivanova, E. P. et al. Natural Bactericidal Surfaces: Mechanical Rupture of Pseudomonas aeruginosa Cells by Cicada Wings. Small 8, 2489–2494 (2012).
4. Ivanova, E. P. et al. Bactericidal activity of black silicon. Nat Commun 4, 2838 (2013).