Antimicrobial Surfaces: Battling Bacteria on the Nanoscale

Germs are everywhere, including where we least want them. Bacteria can easily cause serious disease when they make their way onto medical equipment such as implants and catheters, or even when they are just sitting on surfaces such as door knobs and buttons. The  most obvious solution is to apply antibacterial agents like bleach, iodine, or antibiotic drugs to kill all of the germs. These agents, however, can be almost as unhealthy for us as they are for the germs. Additionally, they can pollute the local environment, be that the tissue around a hip implant or the water reservoir for nearby towns and cities. Lastly, owing to the emergence of drug-resistant “super bacteria,” there is a need for effective approaches that avoid antibiotics; antibiotics will never be able to kill every germ, and the ones that survive become more and more resistant to antibacterial agents. The solution requires antibacterial surfaces that don’t use antibiotics or other toxic chemical agents.

Nature already offers insights towards a solution, as exhibited by superhydrophobic lotus leaves or anti-reflective moth’s eyes. Surfaces with natural antibacterial properties can be found in, or rather, on sharks and cicadas. Close inspection reveals why: scanning electron microscopy (SEM) images taken at NCSU’s Analytical Instrumentation Facility shows that these surfaces are covered with nanoscale features (Figure 1). The microstructures on the shark’s skin prevent bacteria from adhering to the surface, making the surface “anti-fouling.” This is why you never see a shark covered in algae, while turtles are often covered in an undesirable layer of slime. Through a deadlier effect, the nanopillars on cicada wings may puncture and inactivate bacteria, making their surfaces “biocidal.” 

Figure 1: Cicada wings. Photo of a cicada (left) and SEM image of one of its wings (right).

Two categories of antimicrobial surfaces

These two effects of surface structures - anti-fouling and biocidal - present an alternative to the chemical and pharmaceutical attacks of antimicrobial agents (Figure 2). While an anti-fouling surface prevents colonization and formation of a biofilm that leads to further infection, it does not necessarily kill the bacteria. A biocidal surface kills the microbe, but high volumes of debris buildup may cause other issues. 

Figure 2: Types of surfaces. (A) Biofilms can build up on normal, flat surfaces. (B) Microfeatures make a surface anti-fouling by preventing bacterial adhesion. (C) Biocidal surfaces use nanofeatures to kill or inactivate bacteria.

Anti-fouling surfaces

Figure 3: Anti-fouling mechanism. Microfeatures reduce contact area to prevent microbes from anchoring.

Anti-fouling surfaces have many applications, one of the largest being in implants. When a biofilm forms on the surface of an implant, it can cause an infection deep within the body. This is the most common reason implants fail. If the surface of the implant can be functionalized so that bacteria does not stick while not killing the healthy cells around it, the rate of implant failure could be drastically decreased.

The efficacy of a patterned surface depends on the scale of its features relative to the microbe. The average size of a bacterial cell is between one and two micrometers. Microbes can easily colonize features that are larger than the microbes themselves due to the abundance of anchor points to which the microbes can attach and grow. However, when the spacing between the pillars is smaller than the bacteria, the bacteria are unable to stick, as illustrated in Figure 3. For this reason, surfaces with feature sizes between 30 nm and 2 µm have demonstrated a decreased propensity for bacterial adhesion. 

In addition, this same scale of microstructures can create superhydrophobic surfaces when formed into a low-surface-energy material. This low surface energy makes adhesion of almost any molecule difficult, and the resulting dry, barren landscape is particularly inhospitable for microbial life.

Biocidal surfaces

Figure 4: Biocidal mechanism. Nanofeatures puncture membranes or cell walls to kill or inactivate bacteria.

Instead of preventing adhesion, biocidal surfaces actively kill bacteria and prevent it from multiplying. Compared to anti-fouling patterns, biocidal patterns are much smaller. These patterns have nanometer scale pitches - substantially smaller than the average bacteria. Researchers speculate that the sharp points at the top of these features can pierce the membrane of the bacteria, while other mechanisms utilize extremely high aspect ratios that can help rupture the cell wall (Figure 4).

A matter of scale

Since these anti-fouling or biocidal effects depend on the scale of the structure relative to the microbes, and microbes vary in size, it is possible that the same surface is anti-fouling or biocidal for one microbe, but not for another. Animal cells, for example, are much larger than bacterial cells, which is why they are not affected in the same way. For animal cells, nanopatterns can be used on implants to actually help cell proliferation on tissue engineered scaffolds. The nanopatterned surface helps mimic the natural environment that cells typically grow in, allowing them to receive similar signals from their environment.   

What SMS Can Do

Smart Material Solutions’ unique patterning technologies can produce highly customizable surface topographies on a variety of materials, including polymers, that could be optimized for anti-fouling or biocidal properties. By producing drum molds for roll-to-roll nanoimprint lithography, we enable large-scale production for medical equipment or industrial applications. SMS currently collaborates with Professor Roger Narayan at the UNC/NC State Joint Department of Biomedical Engineering to study the antimicrobial properties of some of the patterns we have created.