Scientists at Chalmers University of Technology, Sweden, have developed graphene coatings that act as carriers capable of releasing the bactericidal agent usnic acid over prolonged periods, protecting surfaces of implanted biomedical devices from being colonized by pathogenic bacteria.

One of the key challenges when it comes to biomedical devices and implants that are in contact with living tissue for prolonged periods, is protecting their surfaces from being colonized by bacteria, particularly Staphylococcus aureus and Staphylococcus epidermidis.

Some bacteria can form impenetrable surface layers, or “biofilms,” on surgical implants, such as dental and other orthopedic implants, and represent a major problem for healthcare globally. Biofilms are more resistant than free bacteria, and these infections are therefore more difficult to treat, resulting in considerable suffering, and in the worst cases, requiring the removal or replacement of the implants.

Sustained release of antibacterial compounds from coating materials can prevent the formation of bacterial biofilms. The ability of graphene to reversibly interact with water insoluble molecules makes it a promising cargo system for sustained release of such antimicrobial compounds.

Usnic acid (yellow), released from the implant’s graphene coating, kills the bacteria (green), thereby preventing them from forming infectious biofilms on the surface. [Source: Yen Strandqvist/Chalmers University of Technology]
The current findings are reported in the article, “Sustained release of usnic acid from graphene coatings ensures long term antibiotic film protection,” published in the journal Scientific Reports. The study was conducted in the laboratory of Ivan Mijakovic, PhD, professor at the department of biology and biotechnology at Chalmers University of Technology, and funded by Formas and the Swedish Research Council.

The researchers showed, even after the initial burst of usnic acid release from the graphene material, the sustained steady release continues to block the formation of biofilms. Based on the study, the authors propose graphene coatings loaded with usnic acid can serve as effective antibioflm protection on biomedical surfaces.

Santosh Pandit, PhD, postdoctoral researcher at the department of biology and biological engineering at Chalmers University of Technology, is first author on the study. [Source: Johan Bodell/Chalmers University of Technology]
“Through our research, we have succeeded in binding water-insoluble antibacterial molecules to the graphene, and having the molecules release in a controlled, continuous manner from the material,” said Santosh Pandit, PhD, postdoctoral researcher at the department of biology and biological engineering at Chalmers University of Technology, and first author on the study. “This is an essential requirement for the method to work. The way in which we bind the active molecules to the graphene is also very simple and could be easily integrated into industrial processes.”

A variety of water-insoluble, hydrophobic drugs and molecules could potentially be used for their antibacterial properties in coatings. But for these to be used in the body, they must be attached to a biocompatible material, which can be difficult and labor-intensive to manufacture.

“Graphene offers great potential here for interaction with hydrophobic molecules or drugs. When we created our new material, we made use of these properties. The process of binding the antibacterial molecules takes place with the help of ultrasound,” said Pandit.

In this study, Pandit and his team covered graphene with usnic acid, which is extracted from lichens, for example fruticose lichen. Earlier studies established usnic acid’s bactericidal properties. It works by preventing bacteria from synthesizing nucleic acids, particularly RNA synthesis, and thus blocking protein production in the cell.

The authors tested usnic acid for its resistance to the pathogenic bacteria Staphylococcus aureus and Staphylococcus epidermidis, two common culprits for biofilm formation on medical implants. In addition to successful results for integrating the usnic acid into the surface of the graphene material, they also observed that the usnic acid molecules were released in a controlled and continuous manner, thus preventing the formation of biofilms on the surface.

“Even more importantly, our results show that the method for binding the hydrophobic molecules to graphene is simple. It paves the way for more effective antibacterial protection of biomedical products in the future. We are now planning trials where we will explore binding other hydrophobic molecules and drugs with even greater potential to treat or prevent various clinical infections,” said Pandit.

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