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Board Review Wound Care

Cryopreserved Amniotic Membrane Transplantation for Chronic Wound Management

Allen Raphael, DPM

Allen Raphael, DPM discusses his experience with the use of amniotic membranes for chronic wounds. Dr Raphael will present many of his own cases as well as discuss patient selection and application.

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Goals and Objectives
  1. Understand how fetal tissues aid in the healing process
  2. Discuss how to prepare wounds for graft placement
  3. Discuss patient selection and protocols for amniotic membrane use in chronic wounds
  4. Identify different implantation techniques for amniotic membrane
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  • CPME (Credits: 0.5)

    PRESENT eLearning Systems, LLC is approved by the Council on Podiatric Medical Education as a provider of continuing education in podiatric medicine.

    PRESENT eLearning Systems, LLC has approved this activity for a maximum of 0.5 continuing education contact hours.

    Release Date: 03/16/2018 Expiration Date: 12/31/2018

  • Author
  • Allen Raphael, DPM

    Staff Surgeon
    Village Podiatry Centers
    Director of Atlanta Reconstructive Surgery and Limb Preservation Fellowship
    Smyrna, GA

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  • It is the policy of PRESENT e-Learning Systems and it's accreditors to insure balance, independence, objectivity and scientific rigor in all its individually sponsored or jointly sponsored educational programs. All faculty participating in any PRESENT e-Learning Systems sponsored programs are expected to disclose to the program audience any real or apparent conflict(s) of interest that may have a direct bearing on the subject matter of the continuing education program. This pertains to relationships with pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject matter of the presentation topic. The intent of this policy is not to prevent a speaker with a potential conflict of interest from making a presentation. It is merely intended that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts.

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  • Lecture Transcript
  • Male Speaker: I’d like to bring the next speaker up to the podium who is Dr. Allen Raphael. Dr. Raphael attended the University of Richmond and completed his BS in Biology from Kennesaw State University. He is a graduate of Temple University of Podiatric Medicine. He completed his 3-year surgical residency at Atlanta VA which focused on Advanced Diabetic Lymph Salvage in Medical and Surgical Management of the Foot and Ankle. Today, he is going to be talking about Umbilical Cord and Amniotic Membrane Transplantation for Chronic Wound Management. So, Dr. Raphael.

    [Applause]

    Allen Raphael: Alright, everybody still awake? Hi, I’m Allen Raphael from Atlanta, Georgia, just flew in today. I want to talk to you about basically some technology we’ve been using at Atlanta, Georgia. A lot of diabetics in Atlanta, we love our Southern food, it’s all fried, it’s all fattening and frankly, it’s really tasty. I want to talk to you about some different scenarios, some different situations who have been using a cryopreserved umbilical cord tissue. I’ve had the opportunity to use it for about four years and I find that it’s been really a practice changer for me. This is underwater stuff, I just got back from Belize a couple days ago and there’s so much cool stuff underwater. You got to try it one of these days. So everyone’s got an amniotic product, just like 60 plus out there at this point, right? You don’t know which one to use, where to use it, why to use it, who to use it on? A lot of questions about usage and about which one is the best and I’m not here to tell you which one is the best. I’m here to tell you that I think this tissue is a revolutionary technology. We talked about scarless healing. Fetal tissues heal differently than adult tissues. We know that, that’s been proven scientifically and the good thing is we can preserve the biology of these tissues even when implanted in adults. The ultimate goal of the amniotic tissues is to modulate inflammation. We’re not killing inflammation, that’s not the goal. It’s to modulate it, to control it. Because a diabetic foot wound and any kind of wound that’s been chronic essentially is stuck in a place. And it’s an ongoing cascade of inflammation and how amniotic tissue affects that is what’s revolutionary and how it affects it on a cellular level. It seems to transition it from a scarring, adhesion phenotype to more of a regenerative phenotype. I started talking about back this is 1993. So when you have a tissue injury, whether it’s surgically created or sharing from diabetic foot, your wound is going to go a couple of different ways. It’s either going to repair itself via scar, resolving chronic inflammation. It’s going to either regenerate within an exact replication of that tissue. Deficient healing really is a byproduct of a non-resolving chronic inflammation. This people come in to your office, they may have the wound for two days, they’ve had it for two months or two years and these are chronically inflamed wounds. The amniotic tissue essentially has an effect on pro-inflammatory cells. Pro-inflammatory cells essentially are going to increase cell death, they are going to increase anti-inflammatory signals and reduce pro-inflammatory signals and they have plenty studies to show this as well. Ultimately, it’s about decreasing inflammation and the fetal wound environment is really one more of regeneration versus scarring. Okay. The amniotic tissues are electively donated. They’re C-section births. Basically, they’re scheduled C-section births, they’re harvested basically in hospitals all over the country. I like to call it engineer by moms everywhere, okay. I mean, it’s really, it’s natural stuff. It’s available for everybody. The biologic activity seems to be from heavy chain-hyaluronic acid PTX3 and a host of other growth factors. But ultimately, the results are fairly incredible. They come in different forms. You’re going to find dehydrated forms, thin forms, thick forms, forms that are frozen and soaked in this and marinated in barbecue sauce. I mean there are so many different ways that this stuff is created. I’m going to talk about a particular product that I use which just comes in two forms. A thin form which is 100 microns thick, it’s basically frozen and it takes just a few seconds to thaw, and a thicker version which is 1000 microns, about a millimeter thick and this is what I prefer to use honestly in most cases. It’s primarily umbilical cord tissue which has the highest concentration of those growth factors, it’s jelly, it’s really powerful stuff, okay. Who do use these products on? If you decide to put this on anything and everything that walks in to your office from the operating room, you’re probably not doing your patients service but there are wide applications, and I’m going to talk most about diabetic foot. When you intervene with these patients, one of the exclusion criteria, how do you debride these wounds, how they become ready for grafting. I think we tend to get so excited about the technology, we forget about patient management and wound management and that’s a critical to make these tissues work. It doesn’t matter what you put on these things if you don’t know what you are doing for wound management. How do you apply these grafts? You throw them on there? Do you staple them? Do you suture them? When do you apply another one? This is not always a single application. I found that usually, one application every four weeks seems to work for me. It may not work for you, it maybe one application every week and maybe one every three months. Who’s coming up with all these protocols? A lot of these things are coming up with protocols on the fly.

    [05:00]

    Who do you use it on? Pathologic healers, which is 99.99% of your patients, right? If they were good healers, you wouldn’t be seeing them, right? Wouldn’t they come to you? When you intervene, unless it’s a brand new wound, really, I just go right away and go to the operating room and debride them. There’s no reason to wait on these things. Who do you not use it on? Obviously, it make sense, malignancy, active infection, PVD. You don’t want to put tissue on this. It’s like pouring gasoline on a fire. It doesn’t make any sense to do that. Debridement, I lecture up debridement. I like cold steel. I go to the operating room, debride it with a curette, rongeur or tissue nipper. You go deep enough to get the biofilm out which is about 4 millimeters. I’ll go down the bone to procure bleeding if you have to. If it’s not bleeding, you’re not going to get grafting. Aggressively debride it in the operating room, lavage it if you want to. Use a Versajet, use whatever you want to do but clean the heck out of the wound. Ulcerectomy is what you need to do. Typically, the thick stuff is a millimeter thick and it’s pretty spongy. It feels more like calamari actually. I suture usually with Prolene or nylon. In some cases, I’ll use staples. Staples hurt more, they’re hard to take out but in most cases, they’re a lot faster when you have a huge wound. What do you use over the wound? I use non-adherent, non-occlusive dressings. I don’t want anything oily, I don’t want anything sticky. I want something that’s going to just draw moisture away. And for God sakes, don’t put anything cytotoxic on it. You don’t want to put Dakin’s or ionic silver or iodine. You’re just defeating the purpose of putting these tissues on these wounds. How do you change the dressing? How often? It depends on the wound. I mean, these are highly varied. A plantar foot wound drains a lot. A venous leg wound drains a lot. Some of these wounds don’t drain at all. Use your best judgment. I use a lot of absorptive foams and felts and pads to draw the moisture away. Basically, you’ll see the pictures. It adheres to wound but typically, it forms like a cap, almost like a scab actually. It’s just the top part of the graft becomes engorged with blood and it looks like a scab. But you leave it alone, you don’t pick it, you let the biology continue to absorb in here. Now, when do I apply another one? Just anecdotally, I found, it seems to be four weeks or whenever the wound stop shrinking. There’s not a hard and fast rule on this. If this patient is dissolving graft in two weeks and you feel like it’s slowing down, put it on in three weeks. But I don’t think it’s a weekly application for most of these products, I think that’s a bit excessive. Who’s coming up with these protocols? It’s us. We are the ones. We’re the doctors, right? Trust me. I’m your doctor, right? Let’s talk about this guy. This is taken on an iPhone 1 by the way. I apologize for the wonderful image quality there. Thirty-eight-year-old guy, schizophrenic, barber. You don’t know what kind of hair cut you’re going to get when you go see this guy. It’s going to be crazy. Sickle cell, he’s diabetic, he’s a smoker. It’s painful. He was off his meds, I mean, off all meds I mean. Came into the office and he’s had his wound for a long, long time. I’m going to go to the operating room, obviously, this is not a guy who can debride in the clinic. He’s batshit crazy, pardon the French. I’m going to go to the operating room and go and debride him. So, yes. Sharply debride the wound all the way down the fascia. In this case, I applied the graft with suture. I fenestrate it usually with a 15-blade. About a week later you see the little black dark cap or some yellow tissue. Don’t panic, that’s just graft material that’s getting absorbed basically. At three weeks, the wound is highly granular and pain reduction. You’re going to see pain reduction in a lot of these patients. Six weeks, epithelialized. Eight weeks, it’s closed completely. This is a chronic sickle cell wound. He didn’t stop smoking. He didn’t stop being diabetic and he didn’t stop cutting hair. TMAs, they dehisce a lot. They really do, especially people walk on them. Unfortunately, he dehisced the lateral part of the foot, had a pretty late large defect. I did an I&D and started negative pressure therapy which seemed to work very well. I love negative pressure therapy. Intraoperatively, my decision was to go ahead and graft this. You can vac this all day long but eventually need to deliver some biology to the wound. This is one of my first cases here. The lighting was spectacular as you can see. Typically, if I have a tract, I’ll put a pack, extra graft material in the tract. It’s going to work in there. And then I’ll cover it with a non-adherent dressing later. This is the wound contact layer from a PROFORE that you might all remember and throw out every time you do a PROFORE. But that’s actually a very good covering. At two weeks you see in there healing very nicely. At four weeks, it sort of slows down. I’m going to back to the operating room, put another graft on it, four weeks, six weeks, eight weeks. Who of you misses ICD-9 because god, I miss ICD-9. Anyway, really nice guy. He went on to heal very nicely. He’s a cop, actually. He went back to working on the beat and everything which is great. Another guy, my potbellied vegan. I don’t know how you become potbellied if you’re vegan but apparently he was. I don’t know, he eats very fatty vegetables. I don’t know. I know how I got my potbelly. Nutritionally, he was compromised. This guy has got really bad protein levels. He got low serum albumin levels. He’s got PAD but he’s maxed out at this point. Can’t do anything about it. He dehisced his third ray amp site. It looked like this every time he came in. For weeks, I would debride the heck out of this thing, put collagen products and would come back looking yellow. I’m like, I don’t know what’s going to happen here, let’s try some amniotic tissue. Debride, degranulation. If you got a deep defect, put a couple double layers on things, it’s not a problem to do that. Typically, I’ll pack in the defect and I’ll put a second layer on top and suture and fenestrate it. At two weeks, boy, the wound looks different now.

    [10:00]

    It doesn’t look yellow and smelly and fibrotic anymore. At four weeks, it’s basically epithelialized. At eight weeks, it’s remarkable. I mean, this guy is sick. He was 83 years old at the time of the surgery and it healed very nicely from the surgery which was great. This guy, Charcot. He has a midfoot ulcer. It’s been there for a long, long time. He’s a little skinny guy. He’s like 120 pounds. I’ve never seen a skinner Charcot patient in my life. It’s very weird. Local wound care for three months with other docs. It just wasn’t working very well. The tissue in the wound, as you can see, it’s not terribly healthy, okay. Obviously, by mechanics, these wounds are very tough. He needs a recon but he’s not a candidate for it, unfortunately, for a variety of reasons. His cuboid is subluxed plantarly but he’s got no osteo. There’s no issue in terms of infection. Okay, what do we do? Go to the operating room. I love debriding in the operating room because you can get it cleaner than anywhere else. Suture the graft. Fenestrate the graft. About two or three weeks later, it’s dissolved completely in the graft there as you can see on the far right side, okay. And then I do all kinds of arts and crafts in the operating room, I don’t why, I just like doing this stuff. You’ve used felts, take a little offloading. Use a little bit of some Mepilex Ag foam on there, use some felts and let that thing drain through while you’re offloading. But ultimately, what’s the best way to offload them? It’s a total contact, yes. I mean, that seems pretty obvious. I like grafting these and give them a couple of days to incorporate and then go and put them in the TCC afterwards. Well, look how nice and granule that wound is. That’s super healthy. I don’t really like grafting plantar midfoot wounds. It was skin, I don’t think they’re terribly durable. There’s just two different kinds of TCCs. I prefer the one on the left usually just because I feel I can get a better contact. But essentially, TCCs are the way to go from plantar midfoot and even healing forefoot wounds. I think they’re great. And then couple weeks later, of course, the wound is getting smaller because it’s offloaded properly. Imagine that. No more Mr. Charcot guy. He still has Charcot but he doesn’t have the wound anymore, okay. Couple little things here. I’ve meant to cover those little things but they were off. But couple prose of wisdom here. If you have extra graft material with things, don’t waste it, don’t throw it away, it’s very expensive stuff, usually. If you have double layers, you got extra stuff, put it in the pocket, so to speak, that you create with your suture and suture it down there. I’ve got a home healthcare nurse that likes to remove dressings. I’m going to write on that thing, “Do not remove.” If I found out who their name is, I’ll say, “Ramone [Phonetic], do not remove.” And they get really surprised when they see that when they change the dressing. And then I’ll attach the instruction sometimes, “Here’s the graft. Don’t touch it until this date. Here is you put it on. If you mess with it, I’ll be very unhappy.” Interdigital wounds, you see a lot of these especially in the south where there’s lot of heat, okay. Truck driver hadn’t taken off his shoe and God knows how long here. I mean, this is ridiculous, right? Diabetic, no insurance, no access to meds. Interdigital tinea pedis just went absolutely haywire. Obviously, this looks just wonderful. It’s painful, strangely enough. The whole forefoot is denuded, basically top and bottom. He does like cigarettes a lot too, so he’s got that hobby. This is the foot makeover. You’ll notice the nails are cut as well. It’s very important to cut your toenails, I’m just saying. You get all the crap off of there. There’s lot of bioburden, there’s a lot of pseudomonas and tinea. We culture them, biopsied everything, made sure it was clean. I used a thin, in this case, because it was not a very deep wound. I used a thin material and I really like using the green stuff. I won’t say the product name but I’d like to weave it in between toes and use it all the time. This guy did not stop smoking. He did not stop being diabetic. Nothing changed. The biology changed. That’s two weeks. That’s four weeks. That’s six weeks there on the far left side. He’s got skin. Great, thank you. But unfortunately, he’s still driving his truck. This is my lady here. Boy, she’s a total mess. She had her first ray. She didn’t look down for a couple of weeks after healed and shockingly, another also popped up. Somebody decided to just douse this stuff with gentian violet for a while just to cover it up and make it look like it’s grape juice. It was completely fibrotic. It didn’t look very good. This is it after debridement. That doesn’t look like it’s going to survive, right? You like just take those toes off. What are you keeping those on for? Well, actually, there wasn’t a whole lot of neurovascular comprise. What I’ll do here is I’ll just debride the wound. It went down the bone and tendon, took biopsies and cultures, all the good stuff. Suture the graft on. Fenestrate the graft. This is mine, my arts and crafts. This is what you do when you’re bored in the operating room, you make little cut outs and stuff and you wrap it around here. This is actually a great way to absorb the drainage away. I like using this a lot. The first week after surgery, you should see a glistening graft. Second week, little more fibrotic looking. And then as time goes on, rocky team, here we go. When you get that feeling, you get regenerative healing, right? Come on, no. Okay. But as any patient, this is her. Seriously, I mean, she is like, “My blood sugar went quite low, so I had to get it up.” I’m like, “What was low?” 230. I’m like, “Oh, good Lord.” [indecipherable] [14:41] Diet Coke, okay, so we’re fine. Alright, I like turtles. That’s the last dive on our last day, turtles. Okay, oh, no but we’re not done yet. No, but wait, there’s more. But, wait. Thank you. Alright. Couple new techniques. This is some stuff I’ve come up within the operating room because I’m a little ADD and I wanted to try new things. I figure why put a graft on top of a wound? Why not put it under a wound?

    [15:02]

    Let’s talk about implants, not that kind. These are cuff implants, by the way, cuff implants, okay? We have a lot of recurrence of ulcers, right? We need to figure out a way to keep them coming back again, especially plantar foot ulcers, they get anterior migration of the fat pad, they come back all the time. We’re going to talk about implants. This is what happens when you chew tobacco apparently. They put these little studs in your gum, ugh, horrible. The tissue is scarred badly. This is a guy that my wife sent me. She’s a podiatrist too who doesn’t like wounds so that’s great. Chronic test of tibial sesamoid ulcer. He’s got some of equinus. He’s a former smoker. His A1c is okay. He’s got biomechanical issues too. You got to address the biomechanics. You can’t ignore those obviously. My plan is tibial sesamoid planning, TAL and I’m going to implant some graft here. You could put on there but he’s got a very bad atrophy of the fat pad. What I do is I create a tissue pocket. I go percutaneous. It means I create a tissue plane between subq and capsule. What I usually do is I’m going to undermine these two four corners, okay. Now, you think or you’re making the tissue just vascular. As long as you follow it, just hugging that capsule or deep fascia, you’re okay. I tag it with absorbable suture. What I do is I slide the amniotic tissues into that pocket beneath the ulcer, okay. Then, I will perk it and I will pull it through, so inside out, tied under tension, so it parachutes and stays open. Typically, I’ll close this primarily. If there’s a little wound outside too, put a piece of graft on there. Don’t waste the graft. At three weeks, this thing was moving very well. The ulcer healed. I start him off with first MPJ and range of motion exercises, and the fat pad is soft and supple, okay. This is about six weeks that you’re seeing right here, okay. Pretty remarkable. Now, what’s more remarkable is the 16 weeks. Do you see any evidence of a scar or an ulcer? I mean, that’s pretty awesome. Of course, being a diabetic, he’s a repeat customer, so he’s got one on the right side, so I have to do them again. But that’s pretty regenerative healing. I’m not a plastic surgeon but that was pretty amazing to me. Another one, her name is Bunny [Phonetic]. She is a Southern belle. She had a surgery done, plantar plate repair third interspace neuroma. It dehisced, not shockingly, and was open for a long time. Again, you could put it on the wound, but why not put it in the wound. We debride out, map it out, tag it. In this case, I was able to put it centrally beneath the wound and tag it on all four corners, close it primarily. Six weeks later, you see the wound is healed up, and it’s actually nice and cushioned. Now, this is not a filler. It’s not going to stay there forever. But understand that it changes the biology of the tissue. Same thing here, another big guy, renal disease, patients are a nightmare, total nightmare. But he didn’t have an equinus issue, had as a nice big bunion of course. In this case, he gets a 3 by 3 graft. I did a little tibial sesamoid planning on him as well, so you see that on the far right slide. I’m going to slide and cut it into little half a piece there. If you really want to pad the area, put it in a couple of different places. Put it intracapsularly between the med and the sesamoid and also another piece outside as well. You see, they’re called the double layer of the graft on the center slide there. Closing it up, okay. One week, not a whole lot of edema. I want him to move the joint. I think he moved a little bit too aggressively. But ultimately, that’s three weeks in the middle. He dehisced it a little bit. But six weeks, it’s healed up. It has not broken down yet, which is great. I mean this has been about a year and a half later. Quickly, last couple of slides. This lady has a sub met 5 ulcer. Same kind of idea, map it out where you want to implant your zone here. We’re going to have to do our 5th met condylectomy. Take off the nail polish, for god sakes, but I didn’t do that. In this case, you can see what I do. I dangle it basically. Took chandelier kind of thing where I put four of them. Sutures are pulled outside and then tied percutaneously, closing here. The dots will just dissolve. You don’t need to remove those at all. Those will be hydrolyzed. One week, I kind of freaked out when I saw this, like, “Oh, that’s going to die.” But it did not. Thank God. Three weeks later, it looks like this. And 12 weeks later, completely padded and no more ulcer, okay. More creatures. Not done yet. One more technique, the wound vac weave, okay. You cannot put a big thick piece of graft on a wound and put negative pressure on top of it and expect it to work. It just doesn’t work. It has to be in contact with the wound base. So how do you marry these two technologies together? So what I’ll do is I’ll cut strips of this material. Instead of laying it on top of the wound, I cut little strips. Like arts and crafts again, I’m going to put it basically over the area and I’m going to vac over the spaces which are open and are grafted. What happens eventually is it will marbleize within the granulation tissue. Once it gets flat, I’ll put a regular graft without negative pressure therapy and typically heals very nicely. It works great over dehiscences. This guy fell over his dog during his post-op period of his TMA, and shockingly dehisced. I go ahead and debride it. You see metatarsals exposed in the wound. I’ll usually cut this in a needle caddie. I’ll take it and I’ll leave it on with the GranuFoam, in this case, with the sponge. About four days later, the wound is flushed, four days. Now, I know negative pressure works really well but it doesn’t work that well. I think the biology of this tissue actually helps granulation form more quickly. Over time, basically, it’s flushed at one week. I’m not going to put any more graft here.

    [20:01]

    These are dissolving in the wound. I’m going to use an absorptive dressing on top of this. Let the wound heal externally, okay. Light at the end of the tunnel, and it end up healing very nicely here. Stump, there it is. Alright, open first ray, another guy permeative bone. I had to clean this up quite a bit. Again, same kind of idea, wound vac weave. Strips on the sponge, put the sponge on the wound, and essentially the wounds, it becomes marbleized with this tissue. It works really nicely. A couple of weeks later, I should say, it looks like this, and he’s healed up after long and winding road, okay. No more ingrowns anyone. But open TMA suck. I hate getting these, these guillotines. I’m like, “What am I supposed to with this?” Let’s try to vac it of course. But instead of using maybe collagen stuff, I’m going to use this tissue instead, granulation dissolving strips, and he’s back to the OR, okay. Last thing, I did a retrospective study. I did a diabetic foot study here which we discussed diabetic foot ulcers. I had about 32 patients that we put this on, between 18 and 90 years old. We had a nice diabetic population there in Georgia. Exclusion criteria are only the ones that didn’t have four weeks of post surgical outcome measurements, okay. Time to healing, the endpoint, wound closure and number of product applications were the endpoints. We want to see will this make wounds heal faster, okay. Mostly males because we’re dumb males, we don’t go to the doctor. We don’t take care of ourselves. We know. We hear it all the time. Remarkably, 87% healing rate. These are not healthy people, unfortunately. Room to time to closure, it varies on wounds and how long they’re there for. But about half the folks were healed on week number 10. These are studies by some of my cohorts, Dr. Couture and Dr. Caputo. Pretty similar data. Pretty similar results for these guys. Well, I usually use about two applications for most of my wounds, and we’re seeing about 80 to 85% healing rates on these. Thank you so much for your attention. Thanks for inviting me. Have a great night. See you.