Dr. Granick and Dr. Dev discuss the impact of Bioburden and Biofilm on healing and show case examples using Puraply AM at Plastic Surgery, The Meeting.
Good morning everybody. Uh VIP and I are here today to sort of talk about the use of some of the organogenesis products. Uh The thing that I'm concerned about is primarily biofilm and bacterial contamination. So let's get started. So I'm at Rutgers in New Jersey and uh I'm a plastic surgeon. I run a wound center. However, and I do a lot of wound surgery. That's really the main focus of my practice from an academic standpoint. So what we're concerned about in wounds is establishing a viable wound bed. You wanna have uh a wound that is put into a shape where you can put a skin graft on it or put a flap on it if need be uh or an advanced therapy of some sort. So you need to be cognizant of all of the issues that affect wounds and how to prepare wound to maximize the uh the results. So this whole time concept came about uh by a uh a group about 20 years ago, these were the consultants for uh Smith and nephew and uh they put together this time study and that group turned around and became the symposium for uh advanced wound care and that's how the sawc got started. That's the big wound conference that occurs twice a year in the US. Um The problem is when I go and, and talk there, I'm there pretty much every year. I don't address an audience of surgeons. It's almost all uh pediatric and uh medical. So I'm really actually sort of excited to be in front of you guys because uh you really know what's going on. But the principles of wound bed preparation is the same for everybody. And for us, uh the reliance is primarily on surgical debridement. Uh But basically, there are four components that you're looking at the uh nature of the tissue that's there. You need to improve, you gotta get rid of necrosis and fibrous debris and all that junk uh infection, which is what we're gonna concentrate on here today isn't necessarily infection per se, but it's high bacterial counts and uh biofilm. Um when I started this whole business, biofilm wasn't even a concept. Um But it is now moisture balance also really uh important because you get a wound that's uh too saturated and there's too much uh uh diffusion of uh uh exudate that affects the surrounding skin and also impairs the process. And the wound age is basically uh a stagnation of the cells within the chronic wound uh as it is. So we address several challenges. Probably the foremost is bio burden. Uh But then we have other things that have to be taken into consideration. Uh, the comorbidities. I don't have a patient with wounds who doesn't have comorbidities. I don't, I don't know about you guys. Uh, other than for my trauma patients because they're all acute but the chronic patients all have something going on. Uh, it gets pretty complicated dealing with them and then some of the wounds that we see are complex. They're not just simple, flat, easy to treat ulcers. Uh They've got all kinds of dimensions and shapes and it does turn out that uh wounds that are deeper uh and shaped irregularly uh are harder to get healed. Uh So when we establish a viable wound bed for complex surgical wounds, uh these are the challenges uh primarily by burden wound depth, the irregular shape and the loss of subcutaneous tissue, which basically means exposed bones and tendons. Uh That is something that we as plastic surgeons can deal with probably better than any specialty because we've got tools in our bag to cover up exposed bone, uh open fractures uh and issues like that. So, what's the impact on healing? Well, uh I presume everybody's familiar with biofilm, but I'll just go over some of the basics as well. Uh You need to understand what bio bio burden and biofilm are. Uh biofilm actually is an aggregation of bacteria within a protective adherent shell more or less. Uh So what we can do uh is try to avoid that and uh try to treat it when it occurs. Uh The reason for doing that is because the bio burden uh causes a prolongation of the inflammatory phase of healing and disrupts the whole process of wound healing. Now, it creates a hyper prote oly environment. So when you look in a wound that has biofilm in it, uh there's a lot of uh bacterial bio burden, there's neutrophil accumulation. So it, it has that inflammatory effect. Uh The pro inflammatory cytokines are present, uh the enzyme balance is disturbed so that you have more proteolysis situation for healing. So this is a uh slide that sort of shows you the various phases of bacterial presence. The planktonic bacteria or the free floating bacteria, those are relatively easy to treat. They'll work with any kind of topical agent that you put on there, uh once they begin to aggregate, they form colonies and the wound is colonized. So a lot of times uh when a wound is seen in a, in an ed or in a clinic, uh they send them to you and they say this one's infected, but it's really just not an infection as much as it is colonization. Every wound has bacteria in it and they're gonna be colonized at the least. Uh what's really interesting about bacteria is their ability uh to do this quorum, quorum sensing uh process. And what that is is the bacteria have a mechanism for communicating on a sort of primal level and when they detect a dangerous environment from whatever reason and the reason can be the presence of a topical antibiotic, they will aggregate and form a protective shell. And that is biofilm. I did a fair amount of biofilm research. And interestingly in, in my school, the biofilm uh lab is located within the dental school and that is because the whole concept of biofilm came about from dental plaque. So these guys were into it for 20 years before uh the wound community picked it up. So once you have that biofilm, everything sort of changes, uh what you can do is cut it out. And that's probably the thing that we're gonna do. Uh There are other ways to treat it, but the key takeaway is that you need to be aggressive about the breeding it and you need to maintain a wound in the right shape before you're gonna reconstruct it unless you're gonna put something on it immediately. So biofilm begins as they will tell you within 24 hours when I did uh my NIH studies, I was at Walter Reed Army Hospital for research. And that institute uh had a really nice bacterial strain of uh uh staph epidermitis that formed biofilm that was mature within two hours. So it's variable and don't forget, sta e is the primary contaminant that causes wound infections. And that stuff can form a bio thumb really fast. But by three days, you can assume uh that uh biofilm will be formed. So these are somewhat slimy pictures and uh they basically represent what biofilm looks like when you can visualize it. These are the effects of uh a fairly extensive biofilm, you get this sort of slimy yucky surface, uh the sort of black stinky stuff at the bottom of a pressure ulcer and this aggregation of the fibrous debris that occurs in chronic ones. So biofilms are found in about 80% of chronic wounds. I think it's probably much higher than that, probably closer to almost every one of them and in 6% of acute wounds. So, it depends on when you see the acute wound. But one of the problems that uh the military is really concerned with is that a lot of the people who get injured in military situations, get contaminated acute wounds and form biofilms with really uh aggressive bacteria very early on and biofilm will cause chronic inflammation. It elevates proteases which uh uh degrade PDGF and other cytokines. And you can see how uh on the upper image there, there's fibronectin which is uh uh absent from the wound uh in a chronic non healing ulcer because the biofilm has disrupted uh the uh tissue matrix. Uh whereas on the lower picture, you can see the fibronectin has returned when the wound is beginning to heal. So why are bacteria and biofilms so hard to get rid of? Well, primarily it's the uh exo polymeric material that forms the casing around the bacterias. Uh In most cases, it's hydrophobic, so it repels any kind of liquid. Uh It can react chemically and degrade micro biocides, not just antibiotics, but micro biocides that are not antibiotics. Uh can also be degraded like uh H2O 2, which pseudomonas specifically will destroy. Uh they have negative charges uh in the polysaccharides and the DNA which make up the biofilm, uh E PM. Uh they have persisted bacteria. The persistent bacteria are actually bacteria that go into sort of a hibernation state uh where they become metabolically less active. And that further impedes the ability of antibiotics to reach them. Even if they get through the shell, they can't kill a bacteria unless they're metabolically active. Uh oxygen, oxygen diffusion is also limited. And when the metabolically uh inactive, uh bacteria are there, they don't really use that much oxygen, but it also creates a good environment for other bacteria to start uh accumulating. So you actually find that biofilm typically in the free state is not composed of one strain of bacteria. It's usually multiple bacteria. And the other thing that's really interesting is that they can occur different levels in the womb. So when you have an anaerobic bacteria, uh that biofilm that it forms, can be 6 to 8 millimeters deep to the surface. So if you're using a uh technique to debris the surface of the wound, it's not gonna reach it. And uh that's pretty much that slide. So here are some of the solutions to dealing with biofilm. Well, basically, uh these are all the processes that have been identified, they really work with them frequent sharp debridement, uh which is what can be done in a clinic will help. And in all the studies, actually, probably the one that showed it first in a really big study was the granite study. Uh, when the patients on that study, which was looking at PDGF applied topically to uh diabetic foot wounds. Uh what happened was uh the patients who were treated by non surgical wound specialists did worse. And when they looked at the difference between the two, all the surgeons were Deb breeding the wounds and the medical guys were not. And that's uh where it really was first recognized that frequent sharp debridements on weekly visits, uh really helps uh deal with this. At least it keeps it under some control. There are enzymes that specifically degrade biofilm. Uh dispersant B, which is the enzyme that I studied uh uh attacks the PNAG molecule, which is the core structural component of the E PM. And pulmozyme attracts the free DNA, which is also a component uh of the uh E PM. And pulmozyme is commercialized and is used to treat uh cystic fibrosis. Uh because these kids all form biofilm in their uh uh upper airway, lower airway uh tracks and this stuff will clear it out. So you nebulize it and it's very effective surfactants. Uh They have an ability to disrupt biofilm as well. Negative pressure with irrigation. One of the reasons that works and helps clean up wounds is because it is effective on biofilm. Uh biotherapies which is maggots uh works pretty well. Although uh in the US, it's, it's not all that well accepted. The nurses freak out whenever you put maggots on wounds. But uh it really does work and surgical incision, which is what we rely on. And uh you have some options with that. The hydro surgical approach, the direct contact, low frequency ultrasound and also cold steel, which is what we all rely on the most. So let me just explain some of these a little bit for those of you who may not use it or aren't familiar with it. Uh Fluid jet technology uh was developed 15 years ago for this particular use and uh what it did or what it does is it uh creates a high velocity scheme of Saline which can impart a lot of energy. Uh And when it comes into contact uh with a uh uh piece of tissue where the cohesive factor is less than the force imparted by the beam, it will implode. And because of the nature of the uh flow of the via effect will pull it away, you don't even need the suction on the thing. It's pretty amazing. So in order to get a, a water stream that is uh coherent and high powered. You have to force water through uh a chamber into a hole that's the size of a human hair and it comes out as a beam on the end. So if you're looking at a first jet and you see this cute little white line extending from the uh ports to the evacuation tube, uh don't try to touch it or cut your glove off and possibly your finger. So we do see injuries from that. So you have to be careful with that. Uh It is a very high, very high pressure. So here's a sort of a, an image that show shows how this works. So the jet tube is where the saline comes in uh to the head of this device uh goes through that little port 1000 5/1000 of an inch, the size of a human air. And uh it creates a very powerful stream of saline. It holds the tissue because it sort of almost clamps onto the tissue. And you get this vacuum that's occurring because of the speed of this fluid stream through the gap. And that is called inventory effect. It's sort of the same as if you had like leaves on the side of a river and a current in the middle of the leaves get pulled into the river. Same exact thing. So you don't really even need a vacuum on it. It cuts and removes things at the same time. Ultrasound is a little different. Um In fact, it's totally different. It basically works by transmitting ultrasonic waves into tissue. And um in order to be effective for surgical debris tool, you have to have direct contact. There is a mist that is created by ultrasound and that can be used uh to treat myoho also. Uh but it takes a lot of time, a lot of effort and uh just we're driving you nuts if you had to do it. So the direct contact, low frequency ultrasound uh has a tip frequency of about 22.5000 Hertz, which is, that's how many times it vibrates within a second. So it's really fast. I mean, you don't notice the vibration and it's above the um the human sound perception. Uh don't bring your dog into the or though because they will hear it. Uh It requires a fluid interface in order to transfer ultrasonic energy. So that's why we have saline that gets pumped through the uh device and comes out a little port and the vibrations from the ultrasonic energy uh that's created in the tip of the equipment causes a little misting on the end. And that's, that's been a problem uh for a lot of surgeons and they actually came to me and said, well, what can we do about this? Nobody's using our equipment. And the first time he is it, he said, well, it's the mist. Nobody wants a mist in the air when you're working on a dirty wound. So I work with them, we developed a suction piece for the tip of the machine that will evacuate all the mist when you use it in a technically appropriate way. So how does ultrasonic energy work? Well, it works by micro cavitation and acoustic micro streaming. The micro cavitation is that all these fast oscillations create little air bubbles and the air bubbles get larger and larger and they accumulate energy. And when they burst, they release a tremendous amount of mechanical energy. Acoustic micro streaming is that you also get fluid waves as a result of these vibrations. And they too can have an effect in terms of the breeding of wound. But that's basically how the tissue is affected. So here's an example, this is a patient who had a diabetic uh excuse me, a sickle cell ulcer. And uh you look at that thing, you know, there's a lot of bad stuff going on in that wound. And after one treatment, this is how the patient looked. Uh would I put a skin graft on that? No, wouldn't possibly put a skin graft on that right away because I know that even though we've gotten rid of the biofilm, you're still gonna have a ton of planktonic bacteria in there. So I would typically wait two days, four days to a week and then put a graft on it. And uh the problem is that the bacteria can reform into a biofilm again during that period of time that wasn't really recognized up until, oh, I don't know, maybe 5 to 10 years ago, I mean, that the biofilm reform that fast on a wound, uh, and can repopulate the wound and all these things you think, which are really cleaning it off, whether it's cold steel or it's the, uh, uh, ultrasonic device or, uh, the flu jet, it doesn't matter, they will disrupt biofilm but they won't get rid of the planktonic bacteria. So I was on a search uh for several years looking for something that I could put on as an intermediate um wound covering that would prevent the reformation of biofilm prior to the time that I wanna go ahead and uh put a graft or a flap on the patient. And here's uh how I would excise a woman. I mean, you can look at this woman and realize that it extends way beyond the hole that you can see. And uh when you're done getting all the dead necrotic fat necrosis and everything else involved in it, you end up with this massive one, but there's still gonna be bacteria in it. Uh This is what a wound looks like prior to skin grafting. But even looking at this, you can't be 100% sure there's not biofilm in it. Uh unlikely though this is really pristine looking. So, one of the studies I did was to look at ultrasound clearance of biofilm from metallic implant materials because I see a lot of patients who come in with infected joints and, uh, that's a real big problem. And, uh, in industry, ultrasound is used for cleaning pipes because you can apply it at the factory. Uh, and all the way downstream, all the biofilm that accumulates on the inside of pipes is shaken off and, uh, set free. Uh, and we had a lot of uh, uh incidental reports from orthopedist that uh when they Debre wounds with ultrasonic energy, they were able to uh get the uh uh reconstructions to uh actually stay. And uh the there would not be a recurrence of the infection. So I actually studied that in the lab. And what I found uh was when we uh apply this uh directly uh to uh biofilm that was created. Here's the biofilm you can look at, it looks a little shady. These are shiny uh metallic uh uh components. Uh Some are titanium, some are stainless steel. Those are exactly uh the ones that are used in uh industry for creating implants. So we grew staff epi bioderma uh biofilm on that and then treated it. Uh We also treated it with uh a control which is just dripping the saline from the device on the, on the things. And uh we used uh the ultrasonic energy as well. So when you look here, the ones on the left one stained with crystal violet which will stain uh the E PM of the biofilm, you can see that they're all sort of dark and that's crystal violet you're looking at. So the saline alone isn't gonna get rid of it. However, if you look on the right, you can see that the crystal violet is completely removed and those are nice shiny disks. Again, it really cleans them off nicely. But if you look at what the effluent is, it's a sheet of bacteria, sheet of bacteria, a lawn of bacteria as they like to call it. So, what I found uh to solve this problem uh is uh pure, apply. A uh the AM is antimicrobial and it's not an antibiotic that's in it. It's this material called PHMB. It's been around for a long time. It's very effective on just about all human pathogens and it's uh incorporated into pure apply uh AM and XT. Uh what the XT is, is uh a more highly meshed uh product. Uh The other purely and uh product is MZ which is a micronized powder of pure apply. So what happens? Why is this effective? Well, the broad spectrum affects uh PHMB uh proactively disrupt bio uh bio burden. So what they do is if you put this on a wound that's been freshly debrided and you rinse it off and everything you're still gonna have bacteria there, this sort of prevents uh the reformation of biofilm. Um The micronized product is really nice because you can sort of get it into difficult uh areas I tend to use it when I have a pressure ulcer that I excise. You get this irregular cavity with nooks and crannies and that uh you can't put a sheet of product in there. But this stuff, you can pack it in around the sides of the wounds and it uh it provides a nice matrix. So purely am provides sustained antimicrobial effect in this with, within the product against the broad spectrum of microbes. And you can see here, these are all the uh organisms and there are many others uh that are affected by it. And if you compare it to other dressings like a cell A G which is really uh popular uh primatrix A G promo uh prisma, all of those things uh have an effect but much less uh than purely am. But you notice on the right blast X uh is a little stronger in terms of its antimicrobial ability. However, if you look at cell proliferation, blast, X just kills everything, not just the bacteria that doesn't happen when you use um um purely purely is very safe, safe and effective. So it's been demonstrated that it uh substantially improves the wound bed condition and it supports wound closure. So, wound closure can be in advanced therapy, that's expensive that you wouldn't want to put on a dirty wound uh or a skin graft or a flap. And um as plastic surgeons, I'm sure a lot of you will look at a dirty wound to breed it and then say, well, I'm not gonna put a graft on it right now. I'm gonna wait and let this wound settle down. The way to let it settle down is to put ply on and now we're gonna get into some real world cases. Um VIP Dev is a colleague of ours and he's a plastic surgeon, uh works in Bakersfield, California and uh he is a uh business wizard and an amazing administrator and a really smart guy. He does really good cases and uh he will demonstrate how this stuff is used in real life. Thank you. Thank you, Martin. Thank you. Good morning, ladies and gentlemen, thank you for having me. Um Thank you, Organo Genesis. Um You know, I'm, I'm a private plastic surgeon, but we were on a very large group and uh our large group still does cosmetic surgery, but we still do free flops in the community. And so, uh you know, for, for us, the application or the utilization of pure apply is, is very important. It's really changed the way we practice, especially how we do our flaps, how we do our free flaps and how we prepare uh the flaps or delay flaps when we work with general surgeons, neurosurgeons or anybody else in the community. By the way, if you have questions along the way, please feel free to stop me. I'm happy to. Well, I'm happy to discuss any case. We're all plastic surgeons. So I know if there's any questions about the case, let's just address them and I can uh we can walk through them. It's not a problem. So here's an 80 year old gentleman with invasive squall car, uh invasive uh squamous cell carcinoma. And I worked in collaboration with the neurosurgeon. We removed um the area that's of concern on the left upper slide there all the way down to the uh outer table. That's what I did during the first operation during that operation. Um I sent it off for pathology and the pathology said, look, you know, um looks like it's deeper than what you have. And I'm like, well, I'm down to wood pretty much. What am I gonna do? And so uh I called the neurosurgeon. I said, look, we have to take the outer table off. I mean, it's involving bone. It's, it's invasive squamous cell and that's what we did. That little clear, clear image that you see on top of that is uh the new shield product. It's a, it's an Amnon product uh that I applied. And what I did then is put a um a mesh, a titanium mesh over it because the neurosurgeon felt, felt comfortable covering it up a little bit. And um in between, I thought, well, that product went just underneath that mesh. And uh what we did was we put a negative pressure device on top of it for about a week. And when we waited, we started seeing granulation through it and because I've used Alloderm and so on before in my practices, what I did was uh we placed the Alloderm as you see on there and then put the negative pressure device directly on top of that and the span there is about two week period. And then we just did a skin graft on top of that. Now, you know, what we would have done before is I probably would have done a Lamaster Flap. And I think most of the plastic surgeons in this, in, in this audience could agree that that's probably the right thing to do, you know, in, in private practice, at least where we are. Sometimes patients just don't go for things or, or physiologically, the patients just not ready for it and we don't have the luxury of sending them off to other places sometimes, although we have the connections to the bunky clinic and maybe US C and UCL A. But sometimes things just don't work out that way. In this case, that's what we did. We were able to salvage a case from, from just doing something like that. Um Again, in my hands, it's been, I've, I've been able to utilize it and the reason why is it decreases that bio burden and allows me to get that granulation bed so I could do something a little less um aggressive invasive. Here's another 89 year old gentleman with uh extensive in, in uh invasive squamous cell carcinoma of the left post aic and the superior portion of the neck uh all posteriorly based. And uh for this one, what we did was we did the surgical excision. And then what I did was once I excised it and was left with a defect. I used that micro nice product that doctor Granic talked about in conjunction again with a negative pressure device. And we were able to get this healed up within almost a six week period of time with doing nothing else other than just negative pressure device and getting it healed up along with the micronized pure apply product. And in my hands, I think this allows for better granulation in a quicker amount of time. And we can do this as an outpatient. Normally, we would have had to do a large either um platysmal flap or something of this nature or even a skin graft on it, which was hard to do on this patient just because the patient just didn't want any skin taken anywhere. The family didn't want anything else done and they were happy with the negative pressure device. That's what he looked like six weeks later. Now this is I think probably a little uh something more dear to us. And that is a uh radiation injury, 46 year old female with a history of breast cancer, radiation injury to the breast. And and then of course, subsequent exposure of the implant on the left side. There, you see the implant exposed, uh initially, what we did was we removed, the the implant did a full debridement and you see the drain that we left in there that didn't heal up very well. So what I did was after, after that initial debridement, the radiation injury, I just excised more tissue and then I put the pure apply directly on top of it, remove that drain and put a negative pressure device on top. And that went on, went on to heal incredibly well uh without having to do any other flap with it. Now, of course, this lady at present is about a year and a half out and, and we'll probably start the process again of putting reintroducing an expander. She does, she does not want to use a, a latissimus uh rotational flap even. But I think in my mind and I think most of you would agree that that this patient is primed for a free flap or a deep flap, which uh I think is what we'll probably chalk her into sternal reconstruction. You know, we still get uh you know, although cardiothoracic surgery is really decreased in our area, we have a lot of the um the interventional guys now doing a lot of bypasses and so on the taverns and so on. Now, I think we still do some, some um sternal recons because of failed flaps and this is one of them, you can see the, the bridging of the um of the plates that the cardiothoracic surgeon used. We, we've removed all those plates and uh what I did there was instead of just immediately going to a uh a petrol flap, uh we debrided it. And then if you look on the, the upper slides right here, once I had a good bed, that middle, that the slide to the right there, what you're seeing is the pure apply AM and I placed that directly over the defect. And then I used the negative pressure device. Waited two weeks. Once I had good granulation tissue, I elevated the pectoral flaps as you see and then put them in and then closed over. And again, this allowed me to make sure that this patient that was MRS A positive was truly MRS A negative after two weeks. And the use of negative pressure pure apply. And then I was able to put in my flaps and close up and the patient is doing very well healed out. Uh We're about almost uh 10 months out from him from his progress and he's doing well. Now, this is an interesting case because I worked with the orthopedic surgeons here. And uh this patient had antibiotic beads on the right slide. You can see uh that's the lateral portion of, of the knee. Uh but there's antibiotic beads uh stays uh placed in there and they've kind of calcified around the bone uh but still had existing um polymicrobial uh cultures that are positive and then subsequently MRS a positive. So of course, we're worried about the joint. What I did here was I initially did a delay of the flap. I did a complete debridement. I put purply in it delayed the flap. And that's what that looks like on the left is the delay of the flap. You can see the pur apply placed in, in the uh in the defect. And then I used, I made the incisions for the flap, delayed, it used a negative pressure device and then I closed, closed the flap up on the right side as you can see. And she went on to heal very well uh mobility of the knee. The the orthopedic surgeon did, did do a um a stabilization of the knee and now she's able to use it about a year and a half later. So in summary, what I'd like to state is my in my hands. The use of purply is something that just stabilizes the bed enables me to either do a flap and or a definitive closure. If I don't use a flap, it allows me to place a skin graft and or let it heal secondarily without any subsequent sequi in terms of my uh microbial content. Thank you very much.
