Thank you very much for this question. I think addressing those clinical and systemic factors around periwound and surrounding skin, I think, is really, really important. I think one of the biggest misconceptions in wound care is that the skin surrounding the wound is somehow considered to be a normal skin. But we know that in reality, it is probably some of the most vulnerable skin in the body. It's living under constant stress. It is exposed to wound exudate, to repeated dressing changes, to friction mechanical forces, shearing forces, cleansing adhesives. And of course, this goes on for days, for weeks, and even for months in some cases. One thing that I've noticed throughout my career is that clinicians, they are incredibly good at focusing on the wound itself. We measure the wound, we classify the wound, we take pictures. And I think quite rightly, we pay a lot of attention to the wound bed, the wound bed status. But sometimes the surrounding skin is almost, it becomes forgotten, like the forgotten neighbor, as you can consider it. And yet, it is actually that skin that starts to fail. And the wound almost always becomes quite difficult and more difficult to manage if we forget this surrounding skin.  

From a clinical point of view, it's mainly excessive moisture. That is probably the biggest driver. So, this can be wound exudate, as we know. This can be incontinence. This can be perspiration, lymphatic leakage. And they all, the exposure of the skin to these moisture sources, they disrupt the barrier—the skin barrier and then we do see a cascade. The pH changes, the lipid structure is affected, the skin really becomes softer, but also mechanically weaker and once that barrier is compromised even minor friction or just the removal of an adhesive can cause an injury.  

But I think as you rightly asked, it's just not just one factor. It's really multifactorial. Think, for example, about an older patient with diabetes, chronic edema, venous leg ulcer, heavily exuding. They already have intrinsically a fragile skin. And probably they're less mobile. Their circulation is impaired. Those dressings, they need to be changed frequently. Each of those factors, as I just mentioned, they may be not enough to cause damage, but together they really create what we call a cumulative burden. 

I also would like to mention aging. Aging itself is really an important consideration. So, we know that the older skin will become thinner, less elastic, there's reduced collagen, there's a slower barrier recovery, and it's less resilient to mechanical stress. 

And then, for example, (with) medication like corticosteroids, chronic diseases, nutritional issues, and suddenly a very small external force, being friction or shear, can really produce a significant injury. And over the years, we became more convinced that many skin injuries actually are a systemic or a system problem, much more even than sometimes the biological problem. Another point I would like to raise is that clinicians, they work under enormous pressure. They have high patient loads. They have limited time. They have different vulnerabilities. They change procurement policies. There are inconsistent documentation systems. And that really puts a lot of pressure on our clinicians. And those realities, they influence the care every single day. So I think it's not only the individual biological failure. It is really a result of the healthcare system that makes consistency difficult in the way we deliver the care. And that's my final point to this question. It's ultimately not only the wound that heals in isolation. It's really within what we can call a kind of an ecosystem and the periwound skin is definitely a vital part of that ecosystem.