2012 PRORP Vignette

Title: Electrical Stimulation of Orthopaedic Implants for Eradication of Bacterial Biofilms

Investigator: Mark Ehrensberger, PhD; State University of New York at Buffalo

The primary objective of our work is to develop novel electrical stimulation protocols that could be applied to metallic orthopedic implants to modulate their electrochemical properties and in turn prevent or eradicate device-related biofilm infections.

The particular approach that we've focused on here is looking at titanium as our representative metal orthopedic implant and a strain of gram negative acinetobacter baumannii bacteria that is known to be a prominent pathogen in the military healthcare setting. This bacteria is known to be multi-drug resistant. Certain strains will form biofilms, so planktonic bacteria attach onto a surface and once enough of these bacteria aggregate there, they communicate to each other through electrical or chemical cues and then they become encased in an exopolysaccharide structure. And once they take this form here the mature biofilm may become very highly resistant to antibiotic therapy.

And so our approach is focusing on modulating this interfacial region here to enhance the--the killing or eradication or prevention of this biofilm on titanium implants. Titanium is known to be a very bio-compatible material and that's why it's so utilized. And this oxide film here is really what gives rise to that bio-compatibility. The oxide acts as a barrier to corrosion reactions and the important thing to point out here is that we can modulate the electrochemical properties across this oxide film by applying negative or pathotic stimulation to that implant. And you can see here when we apply these negative voltages we can dramatically change the electrochemical processes that are taking place at that implant site.

So our idea is if we can control the voltage to control these electrochemical properties, what's the influence that that has on the biofilm formation or eradication? And so we took commercially pure titanium coupons and we were forming a biofilm on those coupons. We then extract that coupon and we place it into this ballistics gel chamber to simulate soft tissue coverage of an orthopedic implant. We add a little bit of saline to each of these electrode sites to insure that there is good conductivity around the entire implant. And then we apply various stimulation magnitudes to that titanium sample. Following a-one-hour stimulation we then extract the coupon and we enumerate our CFUs or our Colony Forming Units that are representative of the remaining bacterial biofilm components. And then we also harvest our saline and look at how many bacteria are present in the saline.

And so what we found is that there is a voltage dependent killing rate of biofilm bacteria on the titanium. But I think the most compelling results that we have to date are our pilot data showing this synergistic activity between our stimulation protocol and the role of antibiotic therapy. In our control samples we had a high biofilm formation. When we applied just our antibiotic alone to the saline that surrounded the implant we saw a statistically significant reduction. But still, there was a lot of bacteria present on the coupon.

When we applied stimulation alone with no antibiotics we had a pretty good kill as we had seen in our previous work as well. But when we added the combination of antibiotics and electrical stimulation we had a complete eradication of the biofilm on the titanium coupon. And importantly, this synergistic activity has also been shown in the planktonic or our saline CFUs.

So it appears as though this combination of electrical stimulation and antibiotics will promote the killing of bacteria both in a biofilm and on/in planktonic form. And so we're particularly excited about--about this because this stimulation approach could be widely employed for most of the orthopedic alloys that are in utilization. Stainless steel could be used, cobalt chromium, all of these metals have oxide films that we can control the electrochemical properties of and so we think that this method could be broadly applied in other settings as well.