Chapters Transcript The Role of Micronized Native Collagen in Lower Extremity Complex Surgical Wounds: A PuraPly MZ Case Review Live webinar presented by Dr. Roberto De Los Santos, DPM and Dr. Jeyantt Sankaran, PhD Thank you, Beverly. I'm looking forward to our webinar this evening. Through real world case examples, this webinar will discuss the role of Pure Aly MZ, a native micronized type one collagen in supporting healing and supporting achievement of definitive closure in complex surgical wounds. As for our speakers this evening, we have Doctor Roberto Delos Santos and Doctor Jay Sankaran speaking today. Doctor De Los Santos is a surgical podiatrist in Houston, Texas. He obtained his Doctor of Podiatric Medicine degree from the California School of Podiatric Medicine in San Francisco. He then completed his surgical residency in 4foot and rear foot at HCA Houston Healthcare Kingwood. Dr. Jay has been with Organogenesis for more than 6 years as a field product specialist. He has a PhD in biomedical Engineering from Stony Brook University and a postdoc from UNC. And with that, I will hand it over to Doctor Delos Santos to begin. Thank you, Claire. So, yes, I'm Doctor Delos Santos practicing here in North Houston. Uh, I take a lot of the call from my group and I get to see a lot of interesting, unique cases. And the topic here, key barriers to healing and lower extremity complex surgical wound cases. Hi So with the four different categories see here, uh, unique, commonly seen critical trauma, this is kind of a weekly if not day to day basis. Under the unique, you see the burns, insect bites, spider bites, the hiss of surgical wounds, puncture wounds, bullet wounds. The most commonly seen by other podiatrists can be neuropathic diabetic ulcers, gas gangrene, which is considered an urgent case, dry gangrene, venous stasis ulcers, and pressure injuries. The critical ones that I consider uh are the following two necrotizing fasciitis and pyodermic renosum. And then finally, I do see some foot and ankle trauma, so such as open fracture wounds, lacerations, blunt force trauma struck by a ranch animal. So here in Houston, we do have a lot of uh country folks in collision with a lot of cars. Uh, we do have highways and a lot of bumpy roads. So next slide. So key barriers to healing and complex surgical wounds, if you see in the very first line, the comorbidities, they may impair host defense leading to surgical site infections, complications, and increased costs. So you can see in the first lines an easy alignment and impaired host defenses increase SSI risk and overall there's adverse outcomes. In the second line, the wound ideology, some chronic wounds may have a disregulated inflammatory environment. Leading to delayed healing. So excess MMPs causing growth factors degradation. Finally, in the third bottom row, we have highly exuded wounds, as you can see in the next 2 may impaired ventilation tissue formation with high levels of exitate. Next slide. So, complex wounds and secondary intention healing. As you can see in these pictures, I'm gonna go with the two different types of wounds in the treatment process. So first, complex surgical wounds are generally left open to heal or until a viable wound bed is established, enabling definite closure. Other la or graft. Secondary intentional relies on the formation of new tissue rather than by the approximation of the skin edges itself. So conventional and simple dressing therapy is generally ineffective. Next slide. And I'm gonna pass it over to Doctor J. Thank you. Thank you, Doctor Delos Santos for highlighting some of the complexities in these uh challenging wounds. What I want to do over the next 10 minutes or so is the following. I want to start off by briefly introducing organogenesis portfolio of products that may be applicable for these different challenging wound environments, but I want to focus specifically on the purely portfolio of products and within that primarily just pure apply MZ. I will briefly describe the product, share some of The features and characteristics of PaliMZ and then discuss some preclinical studies that support the use of the product in these in these challenging environments. And then I'll hand it back over to Dr. Delos Santos for him to share some of his thoughts and insights using Pure Apply MZ in some of his most complex cases. So without further ado, organogenesis was founded as a spinoff of MIT in 1985. In 1998, we had one of the first living manufactured cell-based tissue engineered products. Uh, called Alograph. In 2012, we had one of the first BLA approvals for another cell-based product called Gent to it. And since then we've had a whole host of different products. We've had human cell and tissue engineered products, human cell and tissue-based products. Sorry, we've also had A host of Class 2 medical devices and the Pali portfolio products, and we're currently working on BLA for knee osteoarthritis as well. But as I mentioned in this talk, we're going to focus on the pali portfolio of products. So within the pair applied portfolio of products we have Pure Apply AM, Pure Apply SX, and PRApply MZ. Pure Apply AM and Pure Apply SX are sheet-based products. Uh, so they, they're basically sheets of collagen, cross-linked native extracellular matrix collagen with a broad spectrum antimicrobial called PHMB. Purely AM is dual layer, is 4 layer. Purely MZ is are pre-applied micronized as the powdered form of the same native extracellular matrix collagen. This talk is going to focus specifically on pure appli MZ, and we'll talk more about purely MZ in the coming slides. Next slide. As I mentioned previously, para appli MZ or para-applied micronized is the powdered form of the same native extrasate in the matrix collagen. This collagen is derived from forcing small intestinal to mucosa. We purify such a way that we retain just The collagen primarily just collagen one. We retain the native three-dimensional architecture of the collagen and purely MZ. It is generally used to optimize contact conformity and coverage and a regularly shaped wounds. Uh, it is known to support healing. Uh, in the, in the, in these wound environments, it can be used from head to toe in a wide variety of wounds and can be used adjunctively with other products, including Purely AM and Purely SX. Next slide. So what I want to do over the next couple of slides is share some free clinical studies supporting the use of pre-app IMZ in some of these complex environments. Let's start off one of the first questions that comes up. Is IMZ is a micronized product. It's a powdered form of the product. So what is the particle size? So we've done laser diffraction studies or laser light particle size analysis studies where we've looked at purelyMZ. The size of the particle is purelyMZ particles is less than 1000 microns, the size the mean falls somewhere between 250 and 350 microns. The other thing that I did that we did mention previously was that Uh, purely MZ retains the native three dimensional architecture of collagen. To confirm that we've done scanning electron microscopy analysis where we've looked at the band periodicity, which assures us that we retained the native three-dimensional architecture. We've done other calometric assays as well that supports the idea that we retain the native three-dimensional architecture of collagen and Carly MC. Another important part is that PLMZ happens to be a highly absorptive powder. Being highly absorptive, we can make different consistencies out of it. Next slide please. So we found that mixing pair appliMZ with a sterile solution, you can get consistencies like a putty, a paste, or a slurry. And here we have some suggested ratios where you can mix pure appli MC with a sterile solution. Next slide. OK. So one of the other, uh, things that we want to highlight. So when we initially we talked about how pair AliMZ is At 3 in IMZ we retained the native three dimensional architecture of collagen. So why is native extracellular matrix collagen that important? In the literature, it is said that native collagen is a good quencher of proteases that composite collagen products. So we wanted to see if the native architecture collagen and purelyMZ is also a good cruncher of proteases. For that, we ran a series of in vitro experiments. So basically what we did was we took proteases, we took a substrate, we look at how These proteases break down the substrate. And then in the next series of experiments, we basically take these proteases, pre-treat them with purelyMZ, and we see how the pre-treated proteases break down the substrate. And what we actually found was that the pre-treated proteases, the proteases that were pre-treated with paraliMZ did not break down the substrate as well, or they were not as effective in breaking down the substrate. What this shows. Is that purely MZ mitigates the activity of proteases. Now, as you can see in the, in the graph on the right, uh, it is not just that as you increase the concentration of PliMZ you can also see that there's an increase that there's an increased percentage reduction of the activity of proteases as well. Next slide, please. So what is the significance of this elevated protease levels, right? So if we were to think about it in the wound environment, these elevated proteases might have an impact on the cells that are present in the wound environment. So we try to model it using an in vitro assay. So here we culture human fibroblasts in the presence of simulated wound fluid and aggressive simulated wound fluid at that, meaning we add proteases to it, specifically coogenase too. Here we see two different concentrations where we ran the same assay. But what we essentially see is that the viability of fiber lasts in the presence of The, the, the aggressive wound fluid is only 42% as you could see in the very first bar. But in the presence of pure plyMZ, the viability of fiberglass is close to 80%. So what this suggests is that PEIMZ maintains greater cell viability, at least in vitro in this aggressive wound fluid environment. With that, let me quickly recap what we've talked about so far. So we setlyMZ is a powdered form of native extracellular matrix collagen. We saw that the particle size was less than 1000 microns, the average ranging between 250 to 350 microns. We saw that the native architecture of collagen was retained using some SEM analysis and some ometric assays, and we saw why the retention of that native extra say the matrix collagen is important by looking at their ability to quench proteases and why quenching protea is important because Uh, it helps in preserving the viability of fibroblasts and these in vitro experiments. With that, let me wrap up the science portion of the talk and hand it back over to Dr. Bella Santos for him to share some of his thoughts and insights using Pure Ali MZ and it's really complex cases. Dr. Santos. Uh, thank you, Doctor Jay. That was pretty well said. So, um, these are my real world examples. Uh, these are very recent, uh, just this last month in November, I was trying to show how much I utilize it when I do, what different styles I do it and essentially try to answer a question, why do I use it as a podiatrist in the OR? So, first of all, how to apply the purely MZ. First, we have to prepare the wound as seen in the first slide. Uh, we ensure the wound is free of debris and necrotic tissue using standard methods and necessary surgically to bride the wound to ensure that the wound edges contain viable tissue. So a healthy bleeding granular tissue, seen there in number one. Here to the right, number 2, we open and apply the product in the pouch, we remove the container and lightly apply the product over the desired wound area. So you can sprinkle it, you can use your fingers, you can use a cure, um, and essentially have even surface across. So we pour directly from the container as a powder form, hydrate it in a separate sterile container with sterile solutions to form a malleable paste. So there's a powder form paste and one less more consistency that we will show at the end of the presentation. Next, uh, number 3, the dressing. So we apply a non-adherent dressing to maintain a moist wound environment by secondary dressings as appropriate, so 4 by 4 gauze, curli, ABD pad, and non-compressive Ace wrap. Finally, and number 4, we will reassess that the next patient treatment visit, Purli MZ will naturally be reabsorbed into the wound and is not intended to be removed. uh, subsequent application is as discretion for the provider. So, this was uh an elective case, meaning I saw the patient in my clinic. Uh, this is a 45 year old female patient. Uh, essentially, she was a worker that wore steel-toe boots. She said about a year ago, I just got a big knot in the top of my foot. I'll ask her how big? Let's get some X-rays. Once I see the X-rays, I scratch my head cause you see a big giant lump on the top of her midfoot. Um, I've seen something very similar twice before, um, the first time being a giant cell tumor tendency. However, here in this surgical outcome, we have a rare tumor in the, in the foot called myoinflammatory fibroblastic sarcoma. So pretty big words, um, essentially 3 pathologists had to run it here and in California, and this is very rare, uh, not seen very commonly. So this is a rare low grade soft tissue tumor that develops in connective tissue surrounding specifically the muscle. So it presents as a painless swelling, swelling nodule or lobe uh in middle-aged people. Uh, differential diagnosis, you wanna make sure it's giant cell tumor tendon sheet. Uh, gotta rule out fibrosarcoma, and then Hodgkin's lymphoma. The patient, uh, gave him the option, do you want to get an MRI to see exactly what it is, get a more specificity. Or do you want to just proceed and remove it in the surgery? Uh, she wanted to go back to work and just said, I just want to cut out and get back to work, and I said, yes, ma'am, we will do that. So we perform a surgical excision of the tumor, as you can see in the picture on the top right, uh, something big, meaty looking is staring right at me over the extensor hallucis longus tendon. Uh, it was well encapsulated, uh, negative margins, and you can see in the bottom right picture it almost to me looked like a kidney. So essentially we removed it, we identify it, we got all the margins, and we passed it off the sterile field. We applied pre-applied MZ post excision to support a healing environment. You got to remember the skin is very stretchable, so it's been used to having a very big uh nodule or lobe or mass on the top of the foot, so there's a lot of potential space. So here now we removed it all, very healthy, clean. I did do a pathology biopsy of the extensor tendon sheet and the tendon itself to make sure there was nothing traveling up the tendon and which were both negative. Finally, I sprinkled some of the purely MZ powder directly over even across cause there is now a wound deficit and we were able to close it skin to skin with a 20 nylon with no complications. Next night. So, not all the time I get elective procedures. I am on call, so I see a lot of wounds, ulcer, limb salvage, and infections. In this title, the 5th toe gangrene and Hex debriment, we have a 58 year old male patient, vascular status occluded left popliteal artery stent. So he already has vascular compromises had surgeries before, and now it's occluded, meaning 100% closed. Uh, purely MZ post-surgical debridement to support a healing environment was seen here, uh, compared left to the right, and it's eventually, uh, vascular surgery, he uh did intervention. He received a vascular treatment on 11/5 November 5, 2024 and a left common femoral to peroneal bypass, greater sap in his vein. So essentially, the left pinky toe was the one that's causing him a lot of pain. Um, he's had the left, uh, Halus or the big toe wound like that uh Sar uh for a while as well. I, I told him I would like to clean the big toe. I don't wanna remove it or amputate. You know, he wanted to keep as much as he can and I offered to at least clean it. So after the 5th uh digit amputation, if I recall, MRI did show osteomyelitis, we removed it down to the level of the 5th metatarsal phalangeal joint, so the head was exposed, and we put a powder evenly throughout the surgical site and we also put it across the halis dorsal wound. So good blood flow leads to good healing and bad blood flow leads to poor results. So next slide. So that's me applying it with my finger, even throughout, even, uh, I did also use in conjunction, uh the next product called Purely AM which is the sheet form antibiotics coverage, and it did pretty well. I was very satisfied throughout the day. He was there at the hospital for about 2 weeks. So, applied purelyMZ post-surgical and surgery done on October 23, 2024. Nextli. So, this is a dressing change done while he was in the hospital. So it did have a good results if you put a little bit of the powder MZ purply over the bone, you can see a picture on the left where there's no reaction, there's no swelling. It's easygoing, um, easy malleable andentifiable. Here on the right picture shows the 5th digit amputation of the gangrene toe showing no reaction, no swelling, no cause of excess. So, um, I also deal with a lot of uh patients that are considered non-compliant, meaning they don't follow up. Uh, a lot of them are homeless, so I only see them at the hospital in cases where they're urgent. This particular patient, uh, he's been in and out of the hospital for the past 2 years. He had a non-healing amputation site of the right foot, also vascular compromise. So, um, this is a 62 year old male patient, hypertension, peripheral vascular disease, anemia, and chronic kidney disease. Vascular wise, he had a popliteal artery occlusion as well. So me, I did a sharp wound debridement using a 15 blade curette, and in some cases, I use uh a lot of um hands-on debridement to make sure I get all the deep spaces and no infection. And then applied the pre-applied MZ post agreement to support a healing environment as well. The surgery was done on October 24, 2024. So you can see on the picture in the far top right, yes, I sprinkle a lot, uh, over time, and then I close, uh, make sure it's even throughout with a little bit of saline that it's poured in. Next slide. So this is 5 days later. So even though I don't see this patient in my office, I do still have to round on the patient. I still have to do dressing changes in the hospital, and as you can see, he had a great fascinating results where he had bone exposure, tendon exposed, had yellow um inflammatory, uh, essentially non-viable tissue on top of the wound. As you can see here, he has a great granular base bleeding wound uh with good prognosis at this time. So this is October 29, 2024, so two months ago or a month, about a month ago. Next lab. This is him in November 23, 2024. Again, he did not follow up in my clinic, but he returned back to the hospital for other issues. Uh, and this is a most updated picture of him showing still no tendon exposed, no bone exposed. So the, a good bleeding granular base with Purely MZ had great results for this patient and now you can see what I call the purple skin mark edges showing uh baby's skin growing around new skin. Go ahead, next slide. OK. This next patient, this is a, uh, right foot, 5th rate revision amputation. So, uh, again, uh 70 year old male patient with right foot pain, history of diabetes, peripheral vascular disease, neuropathy, so not good sensation. He's still an active smoker. As soon as I went into his room, I can smell the nicotine on him, and he's noncompliant. He doesn't follow up in clinic, doesn't follow instructions. Um, previously had an amputation exactly one month ago for weeks, and he had a stent placed on the posterior tibial artery on October 15th of this year. So, uh, with severe pain, I had to do something. The MRI showed positive of, of bone, uh, lighting up on the uh T2 scan. So I said, how about we try a revision surgery where I remove all the non good looking tissue, uh, try to preserve as much as the bone and attempt to close the wound. So this surgery I performed was November 20th, 2024, so about 2 to 3 weeks ago. Next slide. So I did a more aggressive treatment to try to close the wound. I did resect more of the bone that I needed. Uh, the bone itself wasn't alive anymore at the distal tip of the fifth metatarsal. Uh, I cut or do a saw, uh, through and through osteotomy, dorsal distal planar proximal until I get good granular bleeding of the bone. Once I get that, I feel comfortable saying, OK, we'll remove all the infection. This has a good chance of healing and right before closure, I can, you can see in the picture on the right. So, uh, my attempt, I did, uh, retention stitches to bring the skin edges together. Uh, uh, Everted skin lines noted. This is right at the end of the surgery. I couldn't close at all, unfortunately. Sometimes there is something that, uh, capsule and that tissue exposed, and there you can see a little sheet of purply AM was seen on the distal aspic where the wound was left open. So with that this time instead of using staple gun, I use uh nylon to in the four corners to hold it in place, which we will be removed later in time. So a small wound deficit sutures will purely into microbial wound matrix scene cuts the size with the that wound measuring 3.0 by 2.0 centimeters. Next slide. And this is the patient November 22, 2024, post-op day two, showing no infection, no cellulitis, no reaction using both products, no edema, minimal discharge, swelling, no sign of early ischemic necrosis either. This is a better prognosis and the patient had no pain. So all in all, during the day, he was much happier. Next slide. So finally, this is a video inserted into the wound, all the deep spaces, dust track and tunnel. All that potential space is going to be filled at. Cleared out Any boy So this is where um I try to get creative. Uh, essentially this patient has stepped on, I wanna say uh a nail, and so he had a small uh infection on the bottom. I removed all the infection very minimal, not a lot of drainage or purulence, uh, no m odor, so we caught it pretty early. However, when you remove a lot of the tissue, the skin looks good, but everything in there had to be removed. So we still have a deep layer of fat tissue, uh, wound, um, essentially void. So with that, I decided to mix saline with the pyrili MZ powder and inject it into the site. So we have to make sure there's no infection. Does have a wound deficit internally and we use a syringe, uh, top down, left and right all across and I mix 5 ccs of powder with 5 CC as saline and a 10 cc syringe. So essentially, to answer the question, why do I use this as a podiatrist? So purely MC is easy. It's a powder form and he can form different consistencies, uh, using regular surfaces. It has better conformity, and I use it in conjunction with uh purely AMG and I can see it at early stages while the patient's in the hospital. Um, and thanks to Doctor J. So there's a lot of good things as well with the science format, and yes, you can use it for deep tunnels and superficial wounds in the foot and ankle. So with that, I will pass it on to, I believe Claire, and that is my point of the presentation. Thank you, Doctor Delos Santos. Uh, Back with me, uh, at this point. Uh, there are a couple of questions that have come up. I'm gonna Take those questions in order. I have a couple that came to my cell phone as well, so. What is your typical protocol for follow-up and reapplication? For me specifically, um, if they follow up in clinic, uh, usually, uh, as described, you wanna just remove the outer layer, so I, after discharge of the hospital, I say follow up with me within one week, especially if they're a high risk patient, meaning they're diabetic, or vasculature, chronic kidney disease, or non-compliance. So follow up with me with a week, I do a dressing change. If that looks like a good granular base, I do very minimal debridement. And if I do, um, it doesn't look good, I try to give it at least 1 or 2 additional weeks. If it looks infected, I do 1 or 2 weeks of antibiotics and I say, hey, let's try another bring me in the surgical hospital. So usually within the 2 or 3 week mark, I can see is it doing well or do we need to be more aggressive or change uh the dement format. Very, very interesting. Yeah, just a a follow-up question on this just this just coming directly from me. Uh, so, so has any of this changed with the use of your AMZ, your normal protocol? Are you still following the same kind of protocol? Do you see any differences in the outcomes? Uh, so me personally, uh, if you look at what is the healing at the skin level and underneath, so if you look at the phases, we have hemostasis, the inflammatory phase, the proliferation phase, and finally the remodeling, so with the collagen one at the end, which is stronger. I still think in my mind the 1st 3 days of the strong inflammatory response, so I, if I see too much redness, swelling, uh, or just the, the body pushing away the product. That's when I do a bedside agreement and open it up and flush it out. However, with Purely MZ, uh, I haven't. It's been great. I love using it so much. It's not causing any reaction just within the timeline that the patients in the hospital, I feel comfortable saying yes, it's doing its job. Thank you, doc. OK, so the second one that's come up, what type of secondary dressings are you typically applying over Purli MZ? So, uh, I use adaptic depending on the severity. OK. Uh, I think the next question I think is, is, is slightly different. So it says, do you apply the product as a dry powder or do you hydrate it? So, um, if it's a large boon, I apply it as a dry powder, even and throughout. So, start with the cure wrap, then I put, just use my hands and finger. Um, if it's a, a tiny hole, and I know there's a large wound deficit from an abscess formation, so an abscess is a collection of fluid of infection. Um, I try to not make a big incision. Uh, I try to remove everything, flush it out, clean it out, and I use the injection, the injection format. So if it's a superficial wound powder, uh, and it's, if it's a wide wound powder, if it's a small deep wound, I inject. Published February 12, 2025 Created by
