CME Wound Care

Cryopreserved Umbilical Cord for Diabetic Foot Ulcers Complicated with Osteomyelitis

Wayne Caputo, DPM

Wayne Caputo, DPM discusses the current treatment of osteomyelitis in diabetic foot ulcers and how his center has updated their current practice to more aggressively treat osteomyelitis and use amniotic membrane to enhance healing.

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Goals and Objectives
  1. Identify properties of umbilical cord and amniotic membranes
  2. Discuss the current accepted diagnosis and treatment for osteomyelitis
  3. Discuss Dr. Caputo's current treatment plan for osteomyelitis and the results of his single site study
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  • CPME (Credits: 0.5)

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

  • Author
  • Wayne Caputo, DPM

    Department Chair
    Division of Podiatric Surgery
    Clara Maass Medical Center
    Belleville, New Jersey
    Diplomate, American Board of Podiatric Surgery
    Certification in Foot and Ankle Surgery

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    Wayne Caputo has nothing to disclose.

  • Lecture Transcript
  • Lee: Anyone bringing up Dr. Wayne Caputo. Dr. Caputo is going to talk about umbilical cord for wounds complicated with osteomyelitis. Dr. Caputo is the medical director of Clara Masss Medical Center, wound care center in New Jersey. He runs one of the largest and most successful wound care centers, I mean, at least in the tri-state area, if not in the country. Most Italians, if you tie their hands, they’re not able to talk. Dr. Caputo is a little different. He likes to walk around and talk but he’s going to be stuck behind this podium here for camera purposes. So, I’m very interested to see how he can manage that task. So, welcome.

    Dr. Wayne Caputo: Thank you. Thank you, thank you, Lee, for your kind words. What I’d like to do to you today is speak to you a little bit about Cryopreserved Umbilical Cord and Amnion for Diabetic Foot Ulcers Complicated by Osteomyelitis. I think the treatment of osteomyelitis has been the same for a long period of time. I think, Lee, the first time we saw some change in osteomyelitis was around 1920. Why? Because penicillin was introduced. Up until that time, the treatment of osteomyelitis was always surgical. We went in, we got a deep tissue culture, a bug and treated accordingly. But we’ll see now things have changed. The trade name for cryopreserved umbilical cord and amnion is NEOX. So I’ll tell you a little bit about NEOX and I’ll tell you why NEOX has its salutary effect on wound healing. The second thing I want to do today is release to you or reveal in public the results of a diabetic foot ulcer study complicated by osteomyelitis using NEOX. So with that, we’re going to kick it off. Let’s go. What is this about amniotic membrane and umbilical cord? Well, they kind of work together. They provide protection in utero for the fetus. They act as a matrix. They actually give the wound a roadmap towards healing. They modulate inflammation. Important point, take home point, modulate, reduce inflammation. What have we been trying to do for years? We’ve been trying to go from the hemostatic phase, to the inflammatory phase, to the reparative phase and we haven’t been good at doing it. We’ve been trying to ramrod that for years. So what if we made a U-turn? What if we made a left turn and we started to reduce inflammation? Maybe that’s the way to do it. Maybe we should reduce inflammation. We want to inhibit MMPs, right? MMPs are there, what? They’re out there ready to eat up your growth factors. We need to supply missing elements like growth factors. Also, the cryopreservation process in which the graft is made continues to keep the capacity and the bioactivity of the graft. So, this is a trade secret how it’s done, the freezing process how it’s done and how it’s available to us. We heard a lot about diabetic foot ulcers today. We know what a problem they are. Why they don’t heal quickly? Why you want to heal them quickly? What a course they are? If you look in the book that tells you how to do an amputation it says an infected diabetic foot ulcer on osteomyelitis is a medical and surgical emergency. Do you know if you’re going to have a diabetic foot ulcer and you have an amputation, your five-year mortality is now as high as ovarian carcinoma. So one of the questions, Lee, I always get is why is your center so busy? My center is busy because we go right to the advanced wound care modalities. And I believe that’s why we got the best outcomes. For example, if I say to you, God forbid, you have breast carcinoma, but I’m going to wait 30 days to treat you but I know what works, you would say, this guy belongs in an institution. Something’s wrong with this guy. He’s not thinking correctly. We go right to advanced would care modalities as fast as we can. As fast as we can. What about osteomyelitis? We heard all about diabetic foot ulcers but what about osteomyelitis? Osteomyelitis, Lee, one of the oldest diseases. If you see an old Western movie, you see, they bite on a bullet and they cut his leg off. One of the oldest diseases. But when you look at it, it usually affects the digits of the foot in people who are around 60 years old. Sixty years old, these are people who are productive people. These are workplace people. These are people who have a great deal in a course of utilization of insurance. Great course of doing this and high course into stability. You can imagine, if you work for yourself, and you have to be out because you have to take a t.i.d., q. 8h antibiotic, this is a problem. What do we know? The treatment has been very prevential [phonetic]. We haven’t looked at all.


    I dare to say to anyone in the audience here today, who said we need six to eight weeks of antibiotic therapy for osteomyelitis? Unidentifiable source, I could not find it. If one of you guys can find it, I appreciate if you come to me. Unidentifiable source, but yet we continue to do six to eight weeks of antibiotics since the introduction of penicillin. So we got to do better. We must do better. We got to do better. So we looked at a trial where we might make a left, might reduce inflammation. After all, what is the definition of osteomyelitis in inflammation? Inflammation of bone, localized or generally due to infection, usually pyogenic. So the guys in my center, the infectious disease people when we had our rounds said why don’t we do something to decrease inflammation? And we know one of the properties of amnion, chorion and NEOX is what? Reduction of inflammation. So what if we put something into the wound that reduce inflammation. That’s what we found. We know the old treatment is what? I&D, removal of dead tissue and/or amputation. I was trained 30 years ago by Dr. Frank Esposito, and those guys, back in Brooklyn that said, “You know what you need to do, you need to do wide debridement here. You have to make the chronic wound an acute wound.” This was standard treatment for years. Standard treatment for years. Since 1928, since the introduction of penicillin, it hasn’t changed. Now, where is the dogma come from? January 15, 2015, New England Journal of Medicine rejects 90% of the articles submitted to it. They reject it. And it said, these findings suggest that finally the United States may be controlling the abuse of opioid analgesics. Now, let’s see a show of hands. I’m a clinician, I see people, I’m not an investigator but I see patients. How many people say they have control or we are controlling the opioid analgesic problem? Anybody? It’s spinning out of control just the fact that the patient comes, Lee, to my office, he knows what he wants by name, by generic name, and he knows by dose. Even though he’s got an appointment in a week and maybe he’ll use 30 pills. He needs a hundred 10/35 controlling it. But this is the dogma that’s in the literature. It’s in the literature says we’re controlling this opioid analgesic abuse. I hardly think so. So, in the next slide here, about osteomyelitis. Next slide please.

    Male Speaker 1: You want answers? I think I’m entitled. You want answers.

    Male Speaker 2: I want the truth.

    Male Speaker 1: You can’t handle the truth.

    Dr. Wayne Caputo: The truth, diabetic foot ulcers in osteomyelitis has been what? Parochial? We keep doing the same thing. We keep treating it the same way. We need to change the paradigm of wound healing and that’s what we thought at my center. Maybe we can come up with a better paradigm of wound healing. So with that, we did another study prior to our current study that we’re going to reveal today and we looked at those people with osteomyelitis, they’re those people who had suspected osteomyelitis. We said, “Who gets the osteo, where did they get it, and what are the characteristics?” Who gets it? Where did they get it? So in this way, you could have a strong suspicion. And how do we treat it right now? How do we treat that today? How are we going to do it? Well, you had to have a high index of suspicion. Most people don’t have a high index of suspicion. Ulcer size in my study, the retrospective in my center, ulcer size is greater than 2 centimeter squared, a depth of greater than 3 centimeters, a duration greater than three weeks, positive probe-to-bone sign. We still use post probe positive, probe-to-bone sign. Expose bone if you could see it. We treated osteomyelitis. We didn’t do a bone scan. We didn’t do a biopsy. We didn’t do anything like that. We treated it as osteomyelitis. Blaringly high sed rate. Sed rate greater than 100 suggest osteomyelitis. How about a positive baseline x-ray? You see it all the time. Baseline x-ray shows active osseous destruction indicative of osteomyelitis yet the patient needs an MRI. Why? Why? What are we going to do? Repeat the MRI every six weeks, eight weeks, depending on what’s going on? So you had to have a high index of suspicion. So we looked at over two years, those people who had a high index for suspicion and it had 135 patients that turned out that 62 had positive histopathology, positive histopathology.


    And pathology actually said he has acute osteo, acute and chronic osteomyelitis and we treated those people. We found out where did that come from. Well, most people had big toe osteomyelitis. So chances are, if you have big toe ulcer, your chances are good or having osteomyelitis, fist metatarsal, second toe, how about the heel? But most of the time, this was forefoot and forefoot osteomyelitis. So how do we train that? How do we treat it? So we found that we could treat these people based on location, based on findings. Umbilical cord plus amniotic membrane, what did we say? It provides a matrix, the roadmap, gets the wound heal, inhibits MMPs. We talked about that a little bit this morning in the failure of Promogran study, reduces pain at the site, reduces pain at the site, provides an actual barrier, cover the wound in a mechanical sense, provides growth factors. We said MMPs were waiting there to eat up our growth factors and nonimmunogenic, and guess what? It modulates inflammation, reduce inflammation. We said the definition of osteomyelitis, Lee, is inflammation. Why aren’t we treating inflammation? So that’s what we did. We did an IRB-approved open-label, single-center study. The study surgeon was the primary investigator and we use retrospective approach using cryopreserved umbilical cord to promote healing of diabetic foot ulcers in patient’s complicated with osteomyelitis. So what did we find? Single-center, single investigator. And the objective was to measure the effectiveness and safety of cryopreserved NEOX in promoting wound healing in patients suffering from diabetic foot ulcer. So that was the objective. The design was those people who were treated only at Clara Maass Medical Center by me surgical debridement of the bone and soft tissue. Remember, we wanted the pearls that you’ll take home is, if you have osteo, you want to identify a bug, you don’t want to treat a bug with no baseline microbiology. Those people that had active osseous destruction, we took that active osseous destruction out. If we thought by suspicion that they had osteo, we open the bone cord, takes to access the tubercular bone when it’s reached medullar blood supply and release what? Endothelial progenitor stem cells. We heard a lot about stem cells this morning. Antibiotic therapy was based on deep tissue culture. If you do an I&D, essentially what you want to do is do a C&S of what’s left. You don’t want to treat what’s in the dish, you want to treat what’s in the foot. And we had NEOX CORD 1K transplantation. Remember, we said we are trying to change the paradigm of wound healing. We know we could modulate inflammation, provide growth factors, give the wound a roadmap towards healing and we continue to do that with a treatment protocol including open bone cortex debridement surgical incision and two to eight weeks of I.V. antibiotics and we added NEOX CORD to reduce and modify inflammation. Modulate inflammation, that’s the trouble. So what we did was we looked at the study and found out who had it, five times as many males as females. These people were all around 60 years old. These are workforce people, these are active people. These are people who we said, yes, these people have a great deal of utilization review. We utilize a great deal of disability. These are people who are in the workforce. And we found the ethnicity was essentially well-spread. These were sick people, diabetes, hypertension, gangrene, ischemia, peripheral vascular disease, renal failure, coronary artery diseases. Sick people but workforce people. So we need to change the paradigm. So let’s see what happened. There were a total of 33 wounds. The wound surface was about 15 centimeters square. We said you needed to have high suspicion if it was greater than 2 centimeters squared. These people had big ulcers. The wounds would expose bone, muscle, tendon, ligament. Twenty seven of 33 had this. Twenty seven of 33. So that high index of suspicion was important. Osteomyelitis, 33 of 33 had positive histopathology. And we looked at wound healing, we found that 26 of 33 healed utilizing debridement, deep tissue culture, antibiotic and transplantation of NEOX.


    Six wounds were lost to followup. Wound achieving complete closure, 26 of 27, twenty six of 27. Average time to complete wound healing was about 16 weeks. If we look at it right now, the average time is about 12 weeks from 22%. There was 15 weeks, 50% closed, 21 weeks, 80% closed. Average number of NEOX implantation, 1.1, a small number. A small number of implantations. And the time for closure at 12 weeks, which is really kind of our benchmark was about 30.77%. So we were able to close more ulcers faster with the NEOX implantation. And that’s one of the big questions that people come to me and ask around the company, and so who did the study and how many people were involved? There was no data dredging. I was the operating surgeon, I was the primary investigator. So there is no data dredging. Because people data dredged to make their data look good. This is single center retrospective study. Now, not much more needs to be done but this is hope in a condition that hasn’t been changed in 1928. It’s almost 100 years that we’ve been doing the same thing time and time. If you always do what you always did, you’re always going to get what you always got. So let’s just get to some cases, some quick cases and just like the song “Don’t Ask Me, Just Watch”. Diabetic foot exposed phalange bone at the second toe. She’s sick endstage renal disease, heart attack, the ID person wants complete transmit, complete transmit. She’s already in partial foot amputation which is now the most performed amputation. Four weeks, six weeks. At seven weeks, we did a second application. Now we’ve modified our approach now based on study. We do a second application at 30 days, four weeks. Well, that’s okay. There’s graft in place bottom right hand corner. There’s graft in place. Looks better and better. Actually, that looks regenerative to me. Thirty two weeks complete closure. Endstage renal, cardiac, partial foot amputation on the right. Case number two, 57-year-old, active people. These are people who are in the workforce. PVD, status post bypass, has open amputation. We don’t leave joints. We take joints in or out. We don’t leave joints with exposed cartilage. We get rid of the cartilage. Let’s get rid of the cartilage. Let’s put in NEOX graft on there and see what happens. Graft’s job is absorb any bleeding that’s there. Look at the week number eight, bypass, high risk. You got to get it done quickly, HBO works what? Early on. If you’re a football team, you want to score early and often. Case number three, 63 years old, active people, workforce people, PVD. First rate resection, we don’t leave cartilage. We remove joints. That’s the graft in place. Graft with slow, slow, steady progress. Week number seven. Week number eight, early on, repeat the application, do another debridement, jumpstart the wound, put another NEOX in there. Slow steady progress. Look at that. So with that, I do thank you for your time and attention here this afternoon. I’d like to end with one more slide. Thank you.