Wound care and the giant mutant space lizard analogy

Chronic wounds are those which last more than a matter of days, and can sadly last months or even years. The cost of treating and managing these wounds is extremely high, particularly as care is often delivered in the home.

The underlying causes of chronicity (delayed healing) are complex, as we’ll discuss later, but problems such as poor circulation, immobility and underlying diseases such as diabetes, are often contributory. Unfortunately, the prevalence of chronic wounds is growing due to an aging population and increasing incidence of type 2 diabetes.

Management of chronic wounds has come a long way in the last 30 years. For example, it is now almost universally recognised that chronic wounds need to be kept moist in order to promote cellular healing, and as a result moist wound healing is now the standard of care in the developed world. Many other methods of accelerating wound healing have been investigated, with varying levels of success, but unfortunately our understanding of wound healing and chronicity is rudimentary, particularly when compared with diseases such as cancer which have been intensively studied for many decades.

So why has wound care research lagged behind? The answer is, in part, due to the very fact that chronic wounds are hidden, both practically and socially. They lack prominence yet sadly cause a huge amount of suffering and are a significant drain on health care resources. The good news is, however, that research into chronic wounds is gaining momentum and is being driven by a growing body of passionate and talented research scientists around the world, many of whom are based in the UK.

So why has wound care research lagged behind? The answer is, in part, due to the very fact that chronic wounds are hidden…

Although this research is now ongoing, great heterogeneity still characterises the management of chronic wounds, and the therapies available to clinicians remain relatively unsophisticated, particularly when compared to the high tech tools and drugs used to treat vascular diseases or cancer, for example. The vast majority of wound dressings simply cover the wound and manage the exudate. Even the ‘advanced’ therapeutic dressings now in routine use tend to deliver a single therapy to the wound, such as an anti-microbial compound (such as silver ions), a pain killer (ibuprofen or acetaminophen, for example) or a physical effect (such as negative pressure). Each of these can be beneficial but it’s important to get some perspective on just how unsophisticated these therapies are in the context of wound healing.

Let’s use an analogy… Imagine the complex arrangement of cells, tissues and blood vessels in the skin as the buildings, infrastructure, roads and services within a city district. OK, now imagine that our city has suffered some serious physical disruption, let’s say a giant mutant space lizard has stomped all over the downtown area. Buildings are wrecked, fires are burning, and the place is in chaos.

The first job is to put out the fires and stop the leaking water and gas pipes. Next, the roads must be cleared to establish access in and out of the damaged area. Bulldozers, diggers, demolition cranes and pneumatic hammers will all need to be brought in so that damaged and dangerous buildings can be demolished to make way for new structures. Rubble also needs to be removed so that new brickwork can be laid on solid foundations.

Very similar activities take place in the skin after trauma. Once the bleeding has been stopped, a host of different immune cells will begin to clear away damaged tissues. Enzymes will break down damaged connective tissues before new cells can start to infiltrate, proliferate and repair the damage. New blood vessels will be created to supply the newly formed tissue.

The process of repairing and rebuilding our city is equally complex. Once the initial damage control is completed and access has been established, a massive amount of coordination and planning is required to organise the many different trades and supplies required to rebuild everything from the sewers to the supermarkets. Unfortunately, large civil engineering and building projects are all too often delayed.

Our understanding of chronic wounds is no more complete
Than the mayor’s understanding of why the city’s rebuilding programme is behind schedule.

The rebuilding process is complicated and the repair tasks are interdependent, so it doesn’t take much for the entire project to get held up. Perhaps the demolition crews have accidentally demolished some new buildings by mistake, maybe cement is in short supply, thieves have stolen the copper electrical cables, or someone has ordered the wrong sort of drywall screws. Any of these problems will cause knock-on delays across the site; the bricklayers need the foundations to be completed, the plasterers need the drywall to be finished, the electricians need more copper cable to be delivered and so on.

OK, now imagine you’re the city mayor and you’re coming under pressure to get the downtown area rebuilt as quickly as possible. You’ve heard about the various different problems and the reasons for delays. You need to do something to help, after all it’s your job and people expect you to act decisively and to make things better. Your advisors offer various suggestions: airdropping cement bags across the entire site; banning the use of demolition equipment; carpet bombing drywall screws; or instigating a shoot-on-sight policy for anyone seen carrying copper cable. The problem with all of these interventions is that they’re not only daft but they only target individual aspects of a much bigger and more complex problem.

The same is true when it comes to tackling the problem of chronic wounds. The repair mechanisms are complex and involve a series of sequential, coordinated processes. If any one of these processes is disrupted, becomes unregulated or gets out-of-sync, then the natural wound healing process can stall.

Sadly, our understanding of wound healing biology is currently so incomplete, and our therapies so imprecise, that even the most advanced treatments are akin to airdropping bags of cement onto a building site. For example, we know that the level of proteases (enzymes that break down damaged proteins) are often elevated in chronic non-healing wounds, and so treatments have been developed that seek to counteract excess proteases, but — unsurprisingly — they aren’t a miracle cure. We also know that excessive growth of pathogenic bacteria in the wound isn’t a good thing, so we use dressings that release anti-microbial compounds, such as silver or iodine. Again, these dressings certainly help in some circumstances but not all, and sadly we don’t entirely know why or how to identify those wounds which will respond to a particular therapy.

Our understanding of chronic wounds is no more complete than the mayor’s understanding of why the city’s rebuilding programme is behind schedule. Our current interventions are no more sophisticated.

Today’s biomedical scientists do have an astonishing suite of tools at their disposal to help elucidate the molecular and cellular basis of disease. Encouragingly, these research tools are currently being applied to shed light on the fundamental principles of wound healing. More work is needed to build a more comprehensive picture of the interrelated mechanisms involved in chronicity, but as our understanding grows we can expect better diagnostic and therapeutic tools to be delivered.

Finally, the pharmaceutical and medical technology industries need to recognise that wound care presents subtle but important differences from more mainstream disease areas. Not only is the underlying biology complicated and poorly characterised, but price sensitivity is high and the way in which care is delivered doesn’t always fit standard business models. Recent history contains several examples of where pharma and MedTech companies have overlooked these differences and been left wondering why their products and therapies failed commercially. Thankfully, there are also recent examples of products which have been clinically and commercially very successful in wound care, most notably in negative pressure wound therapy (NPWT). These successes are helping encourage on-going investment in wound care R&D.

The challenges of raising the standard of chronic wound care are considerable. But those who are willing to work hard, to understand the biology, to think creatively and to understand the world of their users, patients and payers, will continue to advance care and improve the lives of many millions of patients whose suffering is often out of sight and out of mind.

This article was taken from issue 6 of Insight magazine. Get your free copy of the latest issue here.