Refractory Wounds: Definition, Etiologic Theories, Pathway for Management, Active Therapies
Skin and Wound Care. Produced by the Emory Nursing Wound Ostomy Continence Nursing Education Center.
Active Therapies: Protease Inhibitors, Matrix, Cell and Tissue Substitutes
Transcript
In this class, we're going to talk about badly behaved wounds.
Speaker A:You know, the wounds where you do everything right?
Speaker A:You identify causative factors and work to correct them.
Speaker A:You look at systemic issues and work on those.
Speaker A:You provide appropriate topical therapy and the wound just sits there, kind of, I don't know, thumbing its nose at you.
Speaker A:So we're going to talk about what could be going wrong, how you go about assessing those wounds and how you move ahead with management.
Speaker A:We're going to define the terms refractory wound and active wound therapy.
Speaker A:We're going to discuss current theories regarding the causative factors for non healing wounds and implications for assessment and management.
Speaker A:And primarily, we're going to discuss the indications and guidelines for use of each of the MMP inhibitors, exogenous growth factors, acellular matrix dressings, cellular skin and tissue substitutes.
Speaker A:These are bioengineered tissues, negative pressure wound therapy, hyperbaric oxygen therapy, estimation, skin grafts and myocutaneous flaps.
Speaker A:So we do have a lot of options for managing difficult wounds.
Speaker A:And that's probably the good news.
Speaker A:You're going to view this video, you're going to read chapter eleven in the core curriculum if you want more background.
Speaker A:And you're going to complete the learning exercises for this section.
Speaker A:So, in part one of this class, we're going to define the term refractory wound.
Speaker A:We're going to define the term active wound therapies.
Speaker A:We're going to discuss the theories regarding etiologic factors for failure to heal.
Speaker A:We're going to provide a pathway for assessment and management of refractory wounds.
Speaker A:And then we're going to start talking about active wound therapies with a focus on protease inhibitors, matrix dressings and cell and tissue substitute products.
Speaker A:So, let's start with terminology.
Speaker A:What do we mean when we say a wound is refractory?
Speaker A:Well, what do we mean in general?
Speaker A:When we use the term refractory?
Speaker A:We mean difficult to manage, something that does not behave as expected.
Speaker A:And that's exactly what we mean when we use the term.
Speaker A:In relationship to a chronic wound, the official definition is a wound with no measurable progress for two weeks despite appropriate comprehensive therapy.
Speaker A:Now, those words are in italics for a reason.
Speaker A:They're a critical component of the definition.
Speaker A:You frequently will have patients who come to your clinic or who you see in the hospital, and when you ask them how long have you had this wound?
Speaker A:They might say three months, four months, five months.
Speaker A:But you cannot consider that wound to be refractory until you have assured appropriate appropriate, comprehensive therapy for at least two weeks.
Speaker A:So if I have a patient who's had a pressure injury for six months, but there's been no attempt to offload the pressure injury, there's been no focus on nutritional management, glucose control, that kind of thing.
Speaker A:It's not yet refractory.
Speaker A:If I put into place a comprehensive management plan and then it fails to progress, then it becomes refractory.
Speaker A:So, just as a review, what is comprehensive therapy?
Speaker A:Identification and correction of causative factors, systemic support for healing and evidence based topical therapy, which includes elimination of necrotic tissue, management of bacterial loads, management of exudate and maintenance of a moist wound surface.
Speaker A:And, of course, as we've discussed earlier, we always are monitoring the response to our comprehensive therapy program and making adjustments as indicated.
Speaker A:So you've done everything right.
Speaker A:The wound is not improving.
Speaker A:Why?
Speaker A:Why would the wound not progress if everything is being done appropriately?
Speaker A:And you see bullet point one, we're not sure that we totally understand.
Speaker A:This is an area of intense study.
Speaker A:Here are some current theories.
Speaker A:Maybe the problem is cellular senescence.
Speaker A:So remember, senescent cells are cells that have lost the ability to reproduce normally or have lost the ability to participate actively in repair processes.
Speaker A:We're unsure at this point in time whether or not we can do anything to take a cell from retired in place to actively working.
Speaker A:That's one thing that is being looked at in current research.
Speaker A:A second theory is that maybe there's inadequate levels of growth factors and cytokines, the molecules that control the repair processes that essentially provide direction to the fibroblasts, endothelial cells and keratinocytes.
Speaker A:Or maybe we have growth factors and cytokines, but it's the wrong combination.
Speaker A:We do know from research that's been done that at any point in the repair process, there's a complex mix of growth factors and cytokines that is constantly changing.
Speaker A:So maybe there's a problem in the mix.
Speaker A:Maybe there's a problem with inadequate levels of growth factors.
Speaker A:Definitely.
Speaker A:We have some evidence that some wounds fail to heal because there are excessive levels of pro inflammatory enzymes, those matrix metalloproteases.
Speaker A:At this point in time, we know that chronic wounds are characterized by high levels of pro inflammatory enzymes.
Speaker A:What we're not sure about is whether or not it's the chicken or the egg.
Speaker A:Do those high levels of mmps actually keep the wound in an inflammatory cycle?
Speaker A:Or are those high levels of pro inflammatory enzymes just reflective of the fact that the wound is stuck in that inflammatory process?
Speaker A:So, as you see a lot that we have left to learn.
Speaker A:And as we learn more, our ability to manage these wounds will, of course, improve.
Speaker A:Here's one big challenge for us at this point, and that is there are no diagnostics for non healing wounds.
Speaker A:So think about how diagnostics drive therapy in healthcare today.
Speaker A:So we send patients for CT scans, for MRI so that we can determine, well, what's the problem and what should we do about it?
Speaker A:When we look at a wound, we try to determine, is this a pressure wound?
Speaker A:Is this a friction wound?
Speaker A:Is this a moisture wound so that we can intervene appropriately?
Speaker A:It would be wonderful if we could do a biopsy or a swab and send it to the lab and say, this wound is not healing.
Speaker A:Tell me why, but we're not there yet.
Speaker A:This is another area of research, is to identify causative factors for failure to heal and then to develop some diagnostics that help us track to those causative factors.
Speaker A:Okay, so what can you do?
Speaker A:I've just given you all the bad news.
Speaker A:We don't really know what's causing failure to heal, and we don't have any good diagnostics.
Speaker A:So what do you know?
Speaker A:You know that you have a wound that's in trouble.
Speaker A:Step one should be to go back and reevaluate your current management plan.
Speaker A:Relook to be sure that you have accurately identified the causative factors and that you've intervened appropriately.
Speaker A:So if you're pretty sure that this is a pressure injury, relook at the support surface in place.
Speaker A:Make sure that the patient is being appropriately repositioned.
Speaker A:Readdress.
Speaker A:What happens when the patient gets up in the chair?
Speaker A:Are they on an appropriate chair cushion, and are they either being shifted every one to 2 hours, or is there time up in the chair being limited?
Speaker A:If you have any concerns at all that the wound might have deteriorated into a malignancy, you should do a biopsy.
Speaker A:So there's two points you need to know about malignant wounds.
Speaker A:First of all, we have good data that says chronic wounds can deteriorate into a malignancy.
Speaker A:And unfortunately, that malignancy may present is hypergranulation tissue.
Speaker A:So if you have a wound that is non healing, you have no idea why it's never, ever wrong to do a biopsy.
Speaker A:Not only does it allow you to rule out malignancy, sometimes it gives you additional information that helps you to identify a previously unrecognized etiology factor.
Speaker A:If you have a wound that presents with hypergranulation tissue and you've treated it with silver nitrate and it does not work that hypergranulation, tissue persists, get a biopsy.
Speaker A:You never, ever want to miss a malignancy.
Speaker A:So we want to maintain a high index of suspicion.
Speaker A:If we're pretty confident that if we've addressed etiologic factors.
Speaker A:The wound is not progressing.
Speaker A:We have no idea.
Speaker A:Why not get a biopsy?
Speaker A:It gives you further information, and it makes sure you don't miss anything important.
Speaker A:Move on to systemic factors.
Speaker A:Go down your list.
Speaker A:Where does the patient stand nutritionally?
Speaker A:Is everything in place?
Speaker A:Are they either stable with their weight or gaining weight?
Speaker A:Are we sure that they're getting enough proteins in?
Speaker A:Are we sure that vitamin and mineral needs are being met?
Speaker A:That kind of thing.
Speaker A:Look at the wound bed.
Speaker A:Is there any evidence of surface infection?
Speaker A:Biofilm formation?
Speaker A:If so, provide a short course of antimicrobial therapy.
Speaker A:Some clinicians just do a short course of dilute dacins to make sure that there's no microscopic necrotic tissue and to knock down bacterial loads.
Speaker A:Look at your wound edges.
Speaker A:Are the wound edges open?
Speaker A:Do you need to retreat those edges to make sure that keratinocytes can migrate and re epithelialize the wound?
Speaker A:It's a hard word to say.
Speaker A:And finally, think about adherence.
Speaker A:So maybe you have a patient with a venous wound, and you have the patient in compression stockings.
Speaker A:Are those compression stockings being worn consistently?
Speaker A:Are those legs being elevated?
Speaker A:So make sure that the plan is actually being implemented.
Speaker A:If you have a patient with a neuropathic wound, is the patient really offloading that wound?
Speaker A:Are they wearing their offloading boots consistently?
Speaker A:Do you need to reassess that whole thing?
Speaker A:Okay, so let's say you've gone back through your management plan.
Speaker A:You've readdressed your etiologic factors.
Speaker A:Let's say you've gotten a biopsy and it was negative and didn't show you anything new.
Speaker A:But you're pretty confident that etiologic factors have been addressed, that the patient is compliant with attention to etiologic factors.
Speaker A:You've relooked at your systemic issues, and, yes, those have been addressed as well.
Speaker A:Topical therapy.
Speaker A:You've redone a short course of antimicrobial therapy or dilute Dakins or whatever, you've reevaluated your wound edges.
Speaker A:Everything's.
Speaker A:All systems go.
Speaker A:So it's just the wound.
Speaker A:Okay.
Speaker A:Once you've made sure that your management plan is appropriate and that there's consistent adherence to your management plan, you're ready to move ahead and to initiate active wound therapy.
Speaker A:So what is that active wound therapy means?
Speaker A:That the products or the procedures that you use have an active impact on the repair process.
Speaker A:Now think back to our last class where we talked about dressing selection, and what did we say most dressings do?
Speaker A:Most dressings provide passive support for wound healing.
Speaker A:They absorb exudate, they wick fluid from tunnels, they maintain a moist wound surface, they provide a bacterial barrier, but they do not actively impact on the repair process.
Speaker A:In contrast, the therapies we're going to discuss in this class have been shown to actively promote healing by stimulating collagen synthesis, by promoting angiogenesis, by increasing the rate of epithelial resurfacing.
Speaker A:Are there any contraindications to active wound therapy?
Speaker A:The only real contraindication is known or suspected malignancy.
Speaker A:And, of course, we don't want to promote cellular activity when we have a known or suspected malignancy.
Speaker A:Are there guidelines for use of active wound therapies?
Speaker A:Yes, and they're pretty straightforward.
Speaker A:First of all, you want to use the current evidence as a basis for selection.
Speaker A:We'll talk about that as we go through.
Speaker A:What's the evidence to support this therapy versus that therapy?
Speaker A:How long should you continue use of inactive wound therapy?
Speaker A:In general, you do a two week initial trial to see, is this going to help?
Speaker A:Is it going to make a difference?
Speaker A:Is the wound going to respond?
Speaker A:Active wound therapies, in general are more expensive, so they should be discontinued.
Speaker A:If there's no improvement in wound status or if you get initial improvement and then the wound plateaus, maybe that therapy has done all it can do for that wound.
Speaker A:Here are some additional guidelines for use of active wound therapies.
Speaker A:First of all, we should use these therapies only for wounds that are clean and uninfected, but not granulating or granulating very slowly, because what active wound therapies are intended to do is to stimulate fibroblast activity, collagen synthesis, neoangiogenesis, and epithelial resurfacing.
Speaker A:They are not really intended to debride wounds or to control bacterial loads, although there are some therapies that can be modified to provide some assistance with those goals of care.
Speaker A:But in general, here's what you want to think.
Speaker A:The inflammatory phase, that first phase of wound healing is all about establishing a clean wound bed.
Speaker A:If you have a necrotic wound, you should focus on debridement, and most debridement approaches are external.
Speaker A:In other words, you're using something like an enzymatic ointment, or you're using a chemical debrider, or you're using conservative, sharp wound debridement or maybe an enzymatic agent.
Speaker A:If the wound is infected, we should be using antimicrobial therapy.
Speaker A:If we have invasive infection or osteo, we have to be using systemic antibiotics.
Speaker A:If we have surface infection and or biofilm formation, we should be doing aggressive cleansing to remove any film from the wound surface, and we should be using antimicrobial dressings.
Speaker A:So if the wound's in the inflammatory phase, focus on establishing a clean wound bed.
Speaker A:If the wound is clean but not granulating and it fails to transition into the proliferative phase, that's when you want to think about active wound therapies.
Speaker A:So really active wound therapies promote the transition from inflammatory phase to proliferative phase and promote granulation, tissue formation and epithelial resurfacing.
Speaker A:So let's talk about the options for active wound therapy.
Speaker A:There's a bunch of them, and we're going to talk briefly about each of these.
Speaker A:So one very commonly used therapeutic approach is protease inhibitors.
Speaker A:These are dressings that reduce the levels of matrix metalloproteases and therefore damp down the inflammatory response.
Speaker A:We have matrix dressings.
Speaker A:These dressings provide a scaffolding for cell migration and attachment.
Speaker A:We have cell and tissue substitutes.
Speaker A:These are dressings that incorporate keratinocytes and or fibroblasts, so they provide the cells and the growth factors to promote healing.
Speaker A:We have exogenous growth factors alone, either in gel form or, or a gel that is derived from the patient's own blood.
Speaker A:So we'll talk about the two different versions of growth factors.
Speaker A:Hyperbaric oxygen therapy may be beneficial if the wound is poorly perfused but viable.
Speaker A:You have to have active plasma flow to the wound bed for hyperbaric oxygen therapy to be effective.
Speaker A:We'll talk more about that.
Speaker A:We'll talk briefly about electrical stimulation, which seems to provide a general stimulus to repair.
Speaker A:We'll talk a good bit about negative pressure wound therapy, which is one of the most commonly used active wound therapies and which, as you probably already know, works via the principles of micro and macro deformation.
Speaker A:And finally, we'll talk about skin grafts and muscle flaps, which actually donate tissue to the wound bed to help close the defect.
Speaker A:So we're going to start with protease inhibitors.
Speaker A:So you probably know these stressins, you might not know them by these labels.
Speaker A:So when we talk about proteases, we are talking about inflammatory enzymes produced by the body itself.
Speaker A:Now, those inflammatory enzymes, those mmps, can be beneficial during the inflammatory phase of repair because what they do is they create pathways in the tissue.
Speaker A:They promote white blood cell activity.
Speaker A:They attract white blood cells to the wombat.
Speaker A:Mmps also control the levels of growth factors and cytokines.
Speaker A:Most mmps are pro inflammatory, though there are some that are anti inflammatory.
Speaker A:The vast majority are pro inflammatory.
Speaker A:So very beneficial during the cleanup phase, but not so helpful once we get to the proliferative phase.
Speaker A:So I sometimes think of them as your demo team, and you think if you have a home or a building that's been damaged and you're going to do renovation, what's the first thing that has to happen?
Speaker A:Well, the demo team has to come in and tear out all of the damage structures.
Speaker A:So if you had fire damage, water damage, whatever, they're going to come in, they're going to take out the damaged drywall, pull up the old carpet, etcetera.
Speaker A:You have to get that done before the repair team can come in, before somebody can come up in and put up new drywall and lay down new flooring, etcetera.
Speaker A:But once you get through the cleanup phase, the demo phase, you want that team out of there.
Speaker A:You don't want them in there trying to tear down drywall while the other team's putting it up.
Speaker A:Same thing in the wound bed.
Speaker A:So those enzymes that are very, very helpful during the inflammatory phase get in the way during the proliferative phase, because they're still in tear down mode, they're still breaking down collagen, they're breaking down growth factors.
Speaker A:That's not helpful.
Speaker A:So normal wound healing is characterized by high levels of MLP's during the inflammatory phase and then a drop off to pretty low levels during the proliferative phase.
Speaker A:Unfortunately, as we have said, chronic wounds and non healing wounds are characterized by persistent high levels of mmps and by a wound that fails to progress from the inflammatory phase to the proliferative phase.
Speaker A:So the question has been asked, well, what would happen if we were able to apply a dressing or a therapy that would reduce the levels of the mmps, take them out of there, take them out of action, so that there's no interference to fibroblast activity.
Speaker A:There's nothing breaking down growth factors.
Speaker A:And that's what we have.
Speaker A:We now have some dressings that can do that, that can inhibit protease activity, reduce the activity of proteases in the wound bit.
Speaker A:Unfortunately, what we do not have at this point in time is a diagnostic.
Speaker A:Wouldn't it be helpful if you had a wound that was failing to move ahead?
Speaker A:It looks cling to your naked eye, but it's not granulating.
Speaker A:And it's just been sitting there for one or two weeks.
Speaker A:Wouldn't it be helpful if you could send a little swab or a sample of wound fluid or even a sample of wound tissue?
Speaker A:And if they could say yes?
Speaker A:Here's the problem.
Speaker A:You have really high levels of mmps.
Speaker A:You need to drive those levels down.
Speaker A:Currently, we do not have that diagnostic tool that's available to us at the bedside.
Speaker A:A lot of work has been done in developing that kind of tool, but it's not yet widely available.
Speaker A:So right now, you have to rely on your clinical assessment.
Speaker A:And what does your clinical assessment show you?
Speaker A:You know, that, or you believe that etiologic factors have been corrected.
Speaker A:Your biopsy says no malignancy, systemic factors have all been addressed.
Speaker A:Topical therapy has been appropriately provided.
Speaker A:You've established a clean wound bed.
Speaker A:But the wound is not moving forward into the proliferative phase, is not granulated, and maybe you also have persistent high volumes of exudate.
Speaker A:Would it make sense to do an empiric trial of a protease inhibitor dressing?
Speaker A:Yes, it would.
Speaker A:So what we know that these dressings can do, they reduce the levels of inflammatory mmps and protect the growth factors and the fibroblasts.
Speaker A:Now, there's different types of protease inhibitor dressings on the market.
Speaker A:Most of them are ORC based, and ORC stands for oxidized regenerated cellulose.
Speaker A:And what's important about ORC is that it's incredibly attractive to mmps.
Speaker A:So if you put an Orc based dressing into the wound bed, the mmps are attracted to the dressing, bound by the dressing, and essentially taken out of action.
Speaker A:So that's the most commonly used approach to reducing levels of mmps.
Speaker A:There's another type of dressing that includes polyhydrogenated ionogens, or, as we say, phi.
Speaker A:Okay, and what do those do?
Speaker A:They actually drive down mmp production.
Speaker A:So you can either drive down mmp production or you can bind the mmps and render them inactive.
Speaker A:Either way, what you're doing is you're taking away that inflammatory stimulus, hopefully moving the wound out of the inflammatory phase and into the proliferative phase.
Speaker A:One good thing about your MMP inhibiting dressings is that as a category, they're relatively low cost.
Speaker A:So it's a very reasonable first step in managing a refractory wound is to consider use of a protease inhibiting dressing.
Speaker A:What kind of evidence do we have?
Speaker A:Well, we do know we have some studies, especially with venous ulcers, pressure injuries and diabetic foot ulcers.
Speaker A:That does show improved healing when a protease inhibitor dressing was used as compared to standard moist wound healing.
Speaker A:We need more data.
Speaker A:Definitely.
Speaker A:Still, a very reasonable first step in managing a refractory wound makes a lot more sense than continuing to do what you were doing.
Speaker A:So here are the guidelines.
Speaker A:Here's one type of protease inhibiting dressing.
Speaker A:As we've said, these are indicated for clean wounds that are not granulating or are granulating very, very slowly or clean wounds that are failing to epithelialize.
Speaker A:So you want to cleanse the wound, apply the dressing by manufacturer guidelines and monitor response.
Speaker A:If you see no improvement in two weeks, then you probably want to discontinue use and think about using something different.
Speaker A:Never make sense to keep doing something that's not working.
Speaker A:And I've just given you some examples.
Speaker A:Those aren't the only ones on the market.
Speaker A:So there's some tegaderm matrix dressing as well.
Speaker A:But probably the most commonly used are promigrant, prisma, puricol and puricol plus.
Speaker A:Okay, now we're going to talk about acellular matrix dressings.
Speaker A:Now, when you talk about acellular matrix dressings, these are dressings that provide a scaffolding for the cells.
Speaker A:They allow the cells to migrate and attach to the dressing.
Speaker A:Now, you think if you were a fibroblast and you were just floating around in fluid, you would not be in a position to synthesize collagen.
Speaker A:You need to establish a workstation and gather all of your supplies and begin to synthesize those collagen strands.
Speaker A:So critically important for cells to attach, they cannot reproduce until they attached.
Speaker A:They can't carry out critical processes needed for repair until they attach.
Speaker A:Unfortunately, many times the wound bed provides inadequate attachment sites, especially if your wound bed is not that healthy.
Speaker A:So the benefit of acellular matrix dressings is they provide multiple attachment sites that allow cells to migrate onto the dressing, attach, reproduce and begin to carry out activities critical to repair.
Speaker A:The analogy I sometimes use is, again, go back to your building.
Speaker A:You're putting up a new building, and maybe you're the guy that's going to do the duct work or the wiring, but you get there and the building hasn't even been framed in.
Speaker A:Well, what are you going to attach your ductwork to?
Speaker A:What are you going to attach pipes to?
Speaker A:What are you going to attach wiring to?
Speaker A:You can't.
Speaker A:You have to have that building framed in before you can start doing your attachments.
Speaker A:Same thing with wound healing.
Speaker A:So cells have to attach before they can reproduce, before they can carry out critical repair functions.
Speaker A:That's what a cellular matrix stresses do, is this scaffolding that allows them to migrate and attach.
Speaker A:So it's indicated for wounds that are clean, ready to granulate, but very slow to granulate.
Speaker A:The other thing that you get from these matrix dressings is that they, the matrix structure that scaffolding facilitates cellular communication.
Speaker A:So just like on a construction site, the construction crews, they communicate with each other.
Speaker A:They have to know what this guy's doing because they're working together to create that new building.
Speaker A:Same thing in wound healing, cells have to communicate.
Speaker A:And the matrix dressings promote cell communication and also provide proliferative signals to the cells.
Speaker A:So everything that you need to move the wound ahead, hopefully.
Speaker A:So what are matrix dressings made out of?
Speaker A:Most of them are collagen glycoproteins.
Speaker A:They also contain growth factors.
Speaker A:But if you talk to patients, they'll say, oh, they use that collagen dressing and my wounds started getting better.
Speaker A:Excuse me.
Speaker A:So most of them have collagen or glycoproteins as a primary component.
Speaker A:Some of them are synthetic, but many of them are either porcine, bovine or avian in origin.
Speaker A:So you just have to know, and you have to know if there's any allergies or any religious concerns that you should be aware of.
Speaker A:Important to realize that acellular matrix dressings, as they say, contain no cells for repair.
Speaker A:So they do not contain fibroblasts, they do not contain keratinocytes.
Speaker A:They simply provide the structure.
Speaker A:In some ways, it's an advantage that there are no fibroblasts and no keratinocytes because that means there's no stimulus to an antigen antibody response.
Speaker A:So very well tolerated.
Speaker A:Frequently just the step that is needed, just the assistance that's needed to get the wound over the hump and back into a proliferative in healing mode.
Speaker A:How much evidence do we have?
Speaker A:Mostly case studies, a few small randomized controlled trials.
Speaker A:Again, what wounds have been evaluated?
Speaker A:Primarily pressure injuries and leg ulcers.
Speaker A:But also we're seeing acellular matrix stress induced a lot in open surgical wounds, especially your abdominal wounds.
Speaker A:Sometimes they're used as an alternative to standard mesh and a lot of you know about all the issues with mesh.
Speaker A:So here's the guidelines for use of your acellular matrix dressings.
Speaker A:Just like we've said, you're going to focus on clean wounds.
Speaker A:These are not intended for dirty wounds.
Speaker A:You're going to follow manufacturer's guidelines, always for frequency of application.
Speaker A:But across the board, very important to maintain a moist wound surface and to avoid cytotoxic or debriding agents.
Speaker A:So you're trying to build tissue.
Speaker A:You don't want to put down a matrix dressing and then put down dacins soaked galls on top of it because you're giving mixed signals to the wound and you can actually break down the components of the matrix dressing.
Speaker A:Now, what about those that are used in abdominal wall reconstruction?
Speaker A:Those of you who work in hospitals are going to see this more and more.
Speaker A:You know that there have been major problems with mesh.
Speaker A:So there's a lot of good that's done by mesh.
Speaker A:When you do abdominal wall reconstruction.
Speaker A:If you put mesh down and close the tissue layers over mesh, the hope is that the granulation tissue will literally granulate over the mesh, that the mesh will reinforce and provide strength to the abdominal walls, much like steel reinforced concrete.
Speaker A:The problem is that the mesh that has been widely used is a foreign body.
Speaker A:And so many times we get into issues with inflammatory reactions, infections, we have to go back and remove the mesh.
Speaker A:Sometimes we get mesh eroding organs and causing fistulas.
Speaker A:So mesh has definitely been a mixed blessing.
Speaker A:Wonderful when it works and a disaster when it doesn't.
Speaker A:So you'll find that many surgeons are using these matrix dressings instead because they will be broken down by the body and they're compatible with all body tissues.
Speaker A:They're not going to act a foreign body.
Speaker A:So you might see a wound, they come back from surgery, the wound is open to the fascia level, but you see layers of mesh in the base of the wound.
Speaker A:And sometimes when you read the operative report, you see that multiple layers of mesh were put down, and that's to provide temporary coverage over the fascia until granulation tissue can begin to form.
Speaker A:Now, what we're always monitoring for is we're monitoring for adherence and for vascularization.
Speaker A:One of two things can happen with these matrix dressings when they're used in abdominal wall reconstruction.
Speaker A:Sometimes the biologic, the matrix dressing provides temporary coverage and then sloughs.
Speaker A:But by that time, granulation tissue has.
Speaker A:Other times you will get in growth of vessels and granulation tissue formation that incorporates that acellular matrix stressing.
Speaker A:So we're always assessing for adherence and vascularization.
Speaker A:Is that mesh still adherent or is it beginning to buckle and separate?
Speaker A:Once it starts to buckle and separate, eventually you're going to have to trim it away and you're going to hope you have a healthy bed of granulation tissue underneath, you usually do.
Speaker A:But if you see that the mesh remains adherent and you're starting to see ingrowth of blood vessels, so the mesh is turning from white to pink to red, that's a great sign.
Speaker A:That means that the acellular matrix dressing is being incorporated into the healed wound.
Speaker A:Now there are many acellular matrix dressings on the market that are being used in abdominal wall reconstruction.
Speaker A:In general, you can divide them into two broad categories.
Speaker A:One is unmodified, non cross linked, and the other is modified and cross linked.
Speaker A:So if it's unmodified and non cross linked, it means that the manufacturer took tissue from an avian source, bovine source, whatever, removed all of the cells so that you avoid that antigen antibody response.
Speaker A:So the cells are removed, but otherwise the tissue is not altered, not modified.
Speaker A:And most of those types of matrix dressings, you'll see vascularization within one to two weeks.
Speaker A:They don't provide a lot of strength, they don't provide a lot of resistance to bacteria.
Speaker A:They're primarily there to provide support for granulation tissue formation.
Speaker A:Then there's another type and they're modified and cross linked.
Speaker A:And what that means is that in addition to removing cells and eliminating the potential for an antigen antibody response, the manufacturer has cross linked the collagen fibers to give additional tensile strength, which is beneficial in terms of overall healing and long term hernia prevention.
Speaker A:But these modified cross linked meshes, or matrix stressings, it's a lot longer, takes a lot longer for them to vascularize.
Speaker A:So as you see, it's four weeks or more for vascularization.
Speaker A:So here's your take home message.
Speaker A:If you have a wound that was left open to the fascia and they used acellular matrix dressings, or what they sometimes call biologic mesh dressings, you're always monitoring for two things.
Speaker A:Is the mesh adherent or is it beginning to separate?
Speaker A:And is it vascularizing?
Speaker A:Are you seeing it go from white, yellow to pink, red?
Speaker A:And of course, you're always monitoring for infection, et cetera, et cetera.
Speaker A:But that tells you what's going on with the mesh and is it going to have to be removed or is it going to be incorporated into the healed wound?
Speaker A:Okay, so we've talked about acellular matrix dressings.
Speaker A:Now we're going to talk about cell and tissue substitute products, also known as bioengineered skin substitutes.
Speaker A:These are basically matrix dressings, but these matrix dressings have living cells incorporated into that matrix, stressing either fibroblast or keratinocytes or both.
Speaker A:Now, we talked about that when they make acellular matrix dressings, the whole reason that they took the cells out was to prevent an antigen antibody response, because if you take cells from someone else, from a donor and you put them into my body, my body is going to react and reject.
Speaker A:It's like, where did you get those and why did you bring them home?
Speaker A:Getting them out of here.
Speaker A:So if you're going to use donor cells, you want to minimize that antigen antibody response.
Speaker A:And the way they do that is they derive the donor cells from either neonatal foreskin or amniotic membrane, and that's because those cells do not express the HLA antigen and do not prompt an antigen antibody response.
Speaker A:Response.
Speaker A:So basically you have this bio absorbable matrix, like we've already talked about collagen or some other substrate, but you have all these cells.
Speaker A:So it's like bringing in a temp crew.
Speaker A:So you think when you're really short at work and maybe you normally don't like working with temp nurses, but you're really short, if a temp nurse shows up, you're probably darn glad to see him or her.
Speaker A:And that's what these fibroblasts and keratinocytes basically do.
Speaker A:They're like, hey, we're here to help.
Speaker A:We can make collagen, we can help resurface the wound, et cetera.
Speaker A:And then gradually they're broken down and hopefully the host fibroblasts and keratinocytes take over.
Speaker A:So you've got the matrix, you've got the cells, and you've got growth factors that are produced by the cells to hopefully get the wound back on track and keep it there.
Speaker A:Now, the two most commonly used cell and tissue substitute products are dermal products and bilayered products.
Speaker A:Now, remember, these products are coming onto the market all the time.
Speaker A:So as soon as I say something, it's going to be outdated and you always pay attention to what your manufacturer's reps say.
Speaker A:But at this point in time, the two most commonly used types of cell and tissue substitutes are dermal based products and bilayered.
Speaker A:So let's talk about dermal products.
Speaker A:Here you have your mesh base, your bioabsorbable polyglactin mesh seeded with fibroblasts.
Speaker A:When is this a good choice?
Speaker A:Well, what are you basically going to be doing?
Speaker A:You're going to be stimulating granulation tissue formation.
Speaker A:So it's indicated for full thickness wounds that are not yet ready to epithelialize.
Speaker A:So basically full thickness wounds with some depth, specifically, full thickness diabetic foot ulcers that do not have tendon, bone, or joint exposure and that have been present for at least six weeks and have not responded to other therapies.
Speaker A:Of course, any of these therapies are adjunct only.
Speaker A:You still have to correct tetiologic factors, you still have to provide systemic support.
Speaker A:So when talking about diabetic foot ulcers, that would mean you still have to offload that neuropathic wound, and you still have to provide nutritional support and glycemic control.
Speaker A:Pretty good evidence.
Speaker A:Multiple randomized control trials, although they're low to medium strength of evidence, meaning that we have a number of randomized control trials that have been done.
Speaker A:But when researchers evaluate the quality of the studies, they're not great.
Speaker A:They're still a whole lot better than nothing.
Speaker A:So here are the guidelines for using dermal skin substitutes.
Speaker A:Of course, you want a clean wound bed.
Speaker A:If you've got a necrotic wound, you've got to debride it.
Speaker A:If you've got an infected wound, you have to get bacterial loads under control.
Speaker A:These products come in a frozen state, so you have to thaw by manufacturer's guidelines.
Speaker A:Then you're going to apply to the wound bed.
Speaker A:You're going to cover it with a non adherent contact layer or damp gauze.
Speaker A:You want to maintain hydration, and you want to maintain close adherence to the wound bed so that you've got the fibroblasts in contact with the wound bed where they can work, where they can attache, reproduce and make collagen.
Speaker A:Now, you can do this therapy more than once.
Speaker A:So it's not like, oh, you can apply this one time.
Speaker A:You can actually apply it for up to eight weeks if needed.
Speaker A:And if you're seeing ongoing response, let's talk about bilayered skin equivalents.
Speaker A:When I think about bilayered skin equivalents, so you've got both a dermal and an epidermal layer.
Speaker A:The dermal layer is embedded with fibroblasts, and the epidermal layer contains keratinocytes.
Speaker A:So this bilayered skin equivalent is ready to produce collagen and ready to produce and maintain the epidermal surface.
Speaker A:It's essentially a non surgical skin graft.
Speaker A:So when would it be appropriate?
Speaker A:It would be appropriate for a very shallow, superficial wound that failed to resurface on its own.
Speaker A:And then you would be providing this, as you see in the wound on bottom, essentially, you're covering the wound.
Speaker A:You're giving it donor skin and hoping that it will provide durable closure.
Speaker A:Now, one thing that's different about the bilayer skin equivalent, when you compare it to, say, split thickness skin graft, a split thickness skin graft would contain all normal structures, blood vessels, melanocytes, macrophages, blah, blah, blah.
Speaker A:But this, remember, this is a substitute and it does not contain everything.
Speaker A:So it does contain that collagen matrix, it does contain fibroblasts and keratinocytes, does not contain blood vessels, does not contain melanocytes or macrophages or nerves or epidermal appendages.
Speaker A:So is this area ever going to sweat?
Speaker A:No.
Speaker A:Is there ever going to be hair in a wound, covered and healed with a bilayered skin substitute?
Speaker A:No.
Speaker A:Will you get blood vessels?
Speaker A:Yes, because once you put this bilayered skin substitute in contact with the wound bed and you maintain close adherence, what happens is that the vessels surrounding the wound migrate into the wound bed and create blood flow.
Speaker A:You have to have that happen or you'll lose the graft, the non surgical skin graft.
Speaker A:So, yes, blood vessels are established.
Speaker A:What about pigmentation?
Speaker A:Is it always going to look weird or is it going to pigment to match the surrounding skin?
Speaker A:That's variable.
Speaker A:And some patients, in some wounds, melanocytes do migrate into the skin substitute and it gradually repigments and matches the surrounding skin.
Speaker A:In other patients, it's always this little white area that never pigmented.
Speaker A:So is it as good as the real thing?
Speaker A:No.
Speaker A:Is it a whole lot better than an open wound?
Speaker A:Yes.
Speaker A:So when would you think about using a bilayered skin equivalent, a non surgical skin graft?
Speaker A:In the literature, in the research, it's been used primarily for venous ulcers that have been present for more than a month with very poor progress in resurfacing or for neuropathic ulcers that have now granulated to the surface but are not epithelializing.
Speaker A:We do have multiple randomized controlled trials.
Speaker A:Again, the quality of those studies is not great.
Speaker A:It's poor to medium quality, still better than nothing.
Speaker A:Here are the current guidelines.
Speaker A:You have to have a clean wound bed.
Speaker A:We'll come back to this when we talk about split thickness skin grafts.
Speaker A:If you put this expensive bilayered skin equivalent on a dirty wound, it will slough 90% plus of the time.
Speaker A:So absolutely essential to establish a clean wound bed with good blood flow and low bacterial counts.
Speaker A:Most clinicians either treat one to two weeks prior to application with systemic antibiotics or with topical antimicrobials.
Speaker A:Secondly, really important to create little openings in the dressing to fenestrate the dressing because you have to allow exudate to pass through.
Speaker A:The reason you have to allow exudate to pass through is because this new skin has to be in close contact with the underlying wound bede so that it can get its nutrients and its oxygen from the blood vessels in the underlying wound bed and so that those vessels can begin to penetrate the skin equivalent and to vascularize it.
Speaker A:If you allow fluid to accumulate, it's going to separate the skin from the underlying wound bed and you're going to lose the non surgical skin graft because it won't be nourished.
Speaker A:Now, when you get this from the manufacturer, you're going to see that it comes in a nutrient broth.
Speaker A:You have to keep the skin cells alive until you place it onto a wound with a viable wound base and it can get its nutrients and its oxygen from the underlying wound bed.
Speaker A:Does it matter which side goes down?
Speaker A:I wouldn't even say this, except.
Speaker A:Except I was talking to a nurse who said her physician told her it did not matter.
Speaker A:Yes, it does.
Speaker A:Dermal side down, epidermal side up.
Speaker A:And then you always stabilize it so you can stabilize it.
Speaker A:Some surgeons use staples, others use steri strips, but you always stabilize it and then cover it with a contact layer dressing.
Speaker A:Most of the time one of your silicone contact layer dressings, like we talked about in the last class, then remember how important it is to maintain very tight adherence between the skin graft and the underlying wound beds so that you get ongoing oxygenation and nutritional support to that new tissue.
Speaker A:Two ways to do it.
Speaker A:Either negative pressure wound therapy, so that you're pulling the layers together, or compression therapy, so you're pushing the skin equivalent against the underlying wound bed.
Speaker A:And typically we leave the whole thing undisturbed for two weeks, and then we very carefully remove the outer layers to see what's going on and what kind of take we have.
Speaker A:Okay, so that's part one of this class.
Speaker A:So we've said that a wound is considered refractory when it shows no measurable progress for two weeks despite appropriate comprehensive management.
Speaker A:We're not sure why that happens.
Speaker A:Maybe it's cellular senescence cells that have lost the ability to reproduce and to carry out critical repair processes.
Speaker A:Maybe at some imbalance in the regulatory factors at the cellular or microscopic level.
Speaker A:We do have a pathway for management.
Speaker A:So step one on that management pathway is to very carefully and critically review your management plan.
Speaker A:Make sure etiologic factors have been corrected, do a biopsy.
Speaker A:If there are any concerns at all about possible malignancy or an unrecognized etiologic factor.
Speaker A:Relook at your systemic factors.
Speaker A:Make sure everything's lined up to support healing.
Speaker A:Consider a repeat, short course of antimicrobial therapy to make sure that the bacterial loads at the wound surface are compatible with repair.
Speaker A:Once you've gone through all of that, you want to initiate active wound therapy.
Speaker A:And in part two of this class, we'll go over additional options for active wound therapy.
Speaker A:Thank you.
