Reply To: Dr. Thomas Webster – Biomedical Engineer (Video & Excerpt Available)

The Silent Role of Biofilms in Chronic Disease Forums Biofilm Community Expert Interviews Dr. Thomas Webster – Biomedical Engineer (Video & Excerpt Available) Reply To: Dr. Thomas Webster – Biomedical Engineer (Video & Excerpt Available)

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    Question: What are the main reasons prosthetics fail in human beings and how would you classify these causes of failure?

    Answer: In orthopedics for example, what happens is that the implant separates from bone and that leads to catastrophic failure. Clearly, this could happen while someone is using that implant; hopefully it happens slowly over time and it is diagnosed before the catastrophic separation of the implant from bone.

    Now what causes that implant to separate from bone, there are numerous reasons; one of the most widely talked about reasons in, again I’ll use this hip implant as a model, in the body you often in the hip have this acetabular cup, in which the hip implant rotates, of course usually this acetabular cup is a polymer, this is a metal, so they wear at different rates, and usually the metal wins, the polymer looses, and you get little pieces of polymer that break off, and often times situate between the bone and the implant. The polymer wear debris, as we often call it, causes bone to die and once the bone dies, it begins separating from the implant again possibly at some point leading to a complete separation of the implant from the bone.

    So wear debris failure is certainly a primary concern. Other primary concerns or causes for failure deal with chronic inflammation. So in some patients you see significant scar tissue growth, not bone, but soft scar tissue growth surrounding portions of the implant. This does not obviously does not provide the same mechanical strength that you need and obtain, when you have bone next to the implant.

    Another main reason is infection, and infection unlike the other two, infection is often times an early event that just cascades into long term problems. Wear debris scenario that I mentioned is often times a late term event and chronic inflammations as you can tell by the word, chronic, is often also a later stage problem, but infection is clearly serves a similar problem as inflammation does since it causes bacteria to grow along the implant keeping bone from growing next to the implant. And often times inflammation is caused by biofilms or bacterial infection. And sometimes all these causes are inter-related, .

    Question: What is a biofilm, and how does it matter?

    Answer: Biofilms are extremely detrimental, even the presence of some bacteria on an implant surface is detrimental, because that keeps bone from growing next to the implant. If you have something like bacteria that will keep the bone or the appropriate tissue from growing. What bacteria will try to do is, try to stick to that foreign object if that environment is appropriate, and proliferate much, much faster than any bone cell could ever proliferate, until it reaches a state of biofilm formation, until multi-layers are formed and it kind of, a good way to think about it, it sequesters that area of the implant from the rest of the body. So you really have an impenetrable area that has formed next to the implant and this is why pharmaceutical agents no longer matter once you reach that point is because that agent or drug cannot penetrate the biofilm to expose themselves to then kill bacteria, so there is really a so called sweet spot in which you can begin to kill bacteria once you pass, once the bacteria pass that, you cannot kill them through conventional means.

    The other things that happen underneath a biofilm, if it has formed on something like this titanium, is you get a very aggressive degradation of the metal, or a polymer, or if it was a polymer and because of the environment inside of a biofilm, you will have a lot of corrosive events, which would occur, which would just lead you down this cascade of failure of this negative release of metal ions, to even promote more bacteria to grow, or promote more inflammatory cells to come to the implant surface, etc. And so I was going to say, this is one of the innovative, perhaps, approach to killing a biofilm, has to be ways to penetrate it. So there are ideas in which many researchers are trying to release pharmaceutical agents from the implant out, so that you can have drugs underneath the biofilm, maybe the pH reaches a certain region in that biofilm, and you end up with a polymer which degrades at that pH, a drug is released and kills it from the bottom. That’s challenging, but that’s a good idea. Another idea would be to figure out a way to penetrate the biofilm from the top. If you can’t get it from the bottom, get it from the top. And this is where some groups, including ourselves, have tried to use magnetic nanoparticles and you can direct where the nanoparticles go in the body and you can potentially penetrated that biofilm through that magnetic particles, if you direct them through the biofilm formation, essentially using another type of energy source like magnetism to drive those particles through, because diffusion alone, they would not do that. So then obviously, once the metal nanoparticles gets inside the biofilm, it can then be controlled to release a drug or even in some cases we have seen the nanoparticles enter the bacteria and just without the drug kill the bacteria. So there may be potential use of magnetic nanoparticles to kill a biofilm, once it has formed.

    Question: Can you talk about a little bit about the facts or studies or evidence that supports something you stated that biofilms are difficult to eradicate with pharmaceuticals? Is that generally an understood convention, how is that known now at this stage in time?

    Answer: I think most of us in the academic field, and I hate to speak for all of my colleagues all around the world (laughs), but most of us, we have done studies, in which we have grown biofilms and then tried to add penicillin, gentamycin or some standard type antibacterial agent and

    …there are all kinds of research that I mentioned, including magnetic nanoparticles releasing drugs from the underside of the biofilm that may work; in fact there is data suggesting in the literature that they are working. But the conventional approach of releasing a drug on .

    Question: What about the variability in the actual biofilm composition or bacterial species or even non-bacterial species — does that contribute to the eradication challenge?

    It sure does, well, I think it supports the conclusion why it is so difficult to eradicate a biofilm is that they are diverse — so you really need a drug that acts on Gram positive, Gram negative, you need a drug that first of all penetrate a biofilm, and then you need help in removal of bacteria. When you penetrate a biofilm and release the bacteria, well then now, the bacteria could now be present systemically. So that really would be an issue too. So this really is a complex problem. But in terms of the conventional drugs that are used, they are not working (laughs). Due to heterogeneity, thickness of the biofilm is another sheer quantity of the biofilm that can form on the implant surface — these can be large amounts of bacteria, different types of bacteria which are cross populating, and aiding each other’s growth, but once it becomes sequestered, that’s really the ultimate challenge for us — to decrease that.

    Question: What kinds of pathogens do you see as the biggest problem and the orthopedic area and are there any specific kinds that have been implicated specifically for device failures?

    The ones that are particularly harmful are Staphylococcus bacteria, so is the one I have seen implicated in many clinical scenarios and quite easily they are able to enter the wound sites as they are present on our skin hence the phrase “”, so they are available and around to crawl, so to speak, into wounds and colonize on a foreign surface. You know which are not naturally in our bodies since they don’t possess any anti-infection, anti-bacterial properties. So, the one I have seen implicated a lot is There are other bacteria that people have associated with other types of medical devices such as , is another bacterium, which we personally have also studied and is another common bacterium, which people are trying to inhibit their function on various medical devices.

    This is what makes it more challenging is that there are both Gram negative and Gram positive bacteria responsible for infection. So early on, the idea was that if you just control the surface energy of your implant, you should be able to repel certain bacteria. But if you are talking about bacteria with diverse charges you have the issue of what is the appropriate surface energy to repel those bacteria. So you know, this is why, you know, this is why Mother Nature is so complicated is it’s not necessarily a one strategy to repel all bacteria, but perhaps we need a combination type approach.