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Articles<br>Interviews<br>What's happening in a chronic wound?<br>What's happening in a chronic wound?

Good bacteria, bad bacteria, biofilms and senescent cells...

18 August 2026

Interview with<br>Holly Wilkinson, University of Hull

Part of the show How can chronic wounds cost more than cancer?

holly_wilkinson.jpg<br>Credit:<br>Holly Wilkinson

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But first, we need to look a bit more deeply into the mechanics of what's actually going wrong in a chronic wound to frustrate the healing process. And it turns out that the perfect storm of entrenched infection - with microbes lurking beneath protective chemical shields dubbed "biofilms" - alongside overzealous yet dysfunctional immune responses, a compromised blood supply that limits the delivery of immune cells and raw materials needed for repair, and an inflammatory milieu caused by damaged, "senescent" cells, is the problem. Some, or all of these factors are usually playing a part, and the person who has been unpicking all this to work out how best we can intervene, is the University of Hull's Holly Wilkinson...<br>Holly - So, we'll look inside a diabetic foot ulcer. These are obviously a type of non-healing wound. They're characterised by a lot of infection and also lots of different types of microbes reside in those types of wounds. We will also see that a lot of those microbes are encapsulated in a type of slime, which we tend to call biofilm, and this actually protects those bacteria from our host cells, which might want to fight those bacteria, and it also protects those bacterial cells from antibiotics as well. So, one of the reasons that we end up with really problematic infections in these wounds is because of this slime that encapsulates these bacteria. In those wounds as well, we also see lots of different types of skin cells, and in this environment, it is very inflammatory, so we'll have lots of types of immune cells that are in there, both trying to attack the bacteria that's in those wounds, but also just behaving in the wrong way.<br>Chris - When we look inside this sort of wound, the skin has got multiple layers to it. So, how many layers has this wound gone through, and what effectively happens at the bottom of the wound, like the bottom of the well? What is there? What's it hitting, and what is the body doing about it?<br>Holly - Yeah, so these wounds do go quite deep. So, we go through the layer that we count as the barrier of our skin, which is our epidermis, and we go into the tissue that is underneath that, which is our dermis, and it's the part of our skin that is full of collagen, and it gives our skin that kind of youthful structure. And when you have a wound that fails to heal, you get breakdown of all of that collagen, so we eat away at that nice structure, and it can go quite deep down to kind of the underlying fascia, the underlying muscle, the underlying bone, when these wounds become very, very serious.<br>Chris - The body must sense that somehow. So, how does the body know that that breach is there?<br>Holly - So, what tends to happen as kind of a first-line response is the cells that we have in that barrier layer, they release signals if they become injured. So, they release damage-associated signals, and also we have bacteria on the top of our skin, and our skin cells sense those bacteria, and usually they exist together in harmony, they communicate with each other. But if you get a breach to the barrier, that can throw all of the signals off as well. So, we then also get bacteria-associated signals that shouldn't be there, and that also signals to the body that there's a problem here that we need to solve.

Chris - And what's the body's response? These signals come flooding out of the wound, there's presumably a gradient, they're hottest where the wound is, and the signal dissipates away from the wound. So, how does the body use that, and what's its reaction?<br>Holly - Yes, so there's a few different things that happen all together. It's kind of an orchestrated, if you like, a concert of kind of different instruments that all come together to produce this wound healing response. So, we have activation of the immune system. So, we have kind of sentinel cells that guard the epidermis, that are immune cells, and they get those signals, and then they leave the epidermis, and they migrate out of the skin to go and tell the body that we need to amount an immune response to this, so then all of the new immune cells flood in from the blood. We also have the cells that are in that top layer of the barrier, they also become activated, and usually they're kind of like a brick-and-mortar structure, and they kind of just sit there, solid in their little shape. But when they get activated by these signals, they kind of shimmy away from each other, and become less of a...