The AgNP/AMP nanocomposites (shown by transmission electron microscopy) were physisorbed onto etched Ti surfaces (shown by scanning electron microscopy) where the implant coatings effectively kill bacteria in biofilms of MRSA (LIVE/DEAD assay).
The AgNP/AMP nanocomposites (shown by transmission electron microscopy) were physisorbed onto etched Ti surfaces (shown by scanning electron microscopy) where the implant coatings effectively kill bacteria in biofilms of MRSA (LIVE/DEAD assay).

Bacterial infection is a major cause of orthopedic and dental implant failure. Now researchers have devised an antibacterial coating for implants combining antimicrobial peptides (AMPs) and silver nanoparticles (AgNPs) for dual impact [Ye et al., Acta Biomaterialia 140 (2022) 338-349, https://doi.org/10.1016/j.actbio.2021.12.008].

“Infections associated with orthopedic and dental implants cause high morbidity, elevated costs, and even mortality,” says Zhou Ye of the University of Notre Dame and incoming assistant professor at the University of Hong Kong. “Traditional approaches to prevent and treat implant infections require the administration of antibiotics.”

Increasing bacterial resistance to antibiotics is driving the need for alternatives such as metal ions or nanoparticles, AMPs or cationic polymers that either release antimicrobial agents, induce contact killing or prevent bacterial adhesion and fouling. Until now, coating materials combining these antibacterial approaches have not been applied to orthopedic and dental implants.

“We developed an antimicrobial nanocoating for titanium implants [based on a] combination of two antimicrobial agents: self-assembled short biomolecules with metallic nanoparticles,” explains Conrado Aparicio of UIC Barcelona – Universitat Internacional de Catalunya, co-lead author of the work. “We aimed at exploiting the interplay of different antimicrobial mechanisms and enable synergistic effects for preventing infection around implants.”

The new nanocomposite coating comprises self-assembled nanostructures of the AMP known as GL13K decorated with AgNPs. The self-assembly of AMPs into nanofibrils is triggered in alkaline solution that also contains a suspension of AgNPs. Hydrogen bonding tightly sticks the nanocomposite onto the titanium (Ti) surface of an implant etched to create a nanostructured surface. The approach promises a significant improvement over existing AMP/AgNP coatings, which tend to be weakly bound to Ti surfaces. The new coating material is also more stable than similar AMP/AgNP formulations.

In both lab-based in vitro and in vivo tests in a rat infection model, the hybrid coating shows antimicrobial efficacy for a range of bacterial species one or two orders of magnitude greater than single-agent or control surfaces, respectively. The nanocomposite brings together the local contact killing ability of self-assembled AMPs with the long-range bactericidal effect of AgNPs.

“[The] hybrid… antimicrobial coating improves the relatively low efficacy of current implant coatings, especially when tested in vivo,” points out Ye. “This stable coating favors long and combined effects of the two antimicrobial agents.”

The coating is easy to fabricate and can be stored under vacuum conditions for months without losing bioactivity, say the researchers. As the coating relies on a strong physical interaction with the implant surface, the approach can be translated to other biomedical devices such as catheters, cardiac implantable devices, and ventilators. The AgNPs could also be replaced with other metallic, polymeric or ceramic nanoparticles for a range of different biofunctionalities.