There’s more to wound healing than meets the eye

Dealing with a minor cut or graze is usually pretty straightforward: stop the bleeding, maybe pop on some antiseptic, and leave it to knit together again.

But the situation unfolding under your fresh scab is anything but simple. Healthy wound healing is a tightly choreographed cellular dance, with steps that must take place in order and at the right time. And when those phases drag out or fail to start, minor sores can become painful, enduring ulcers.

We need fast, efficient healing because skin is our main barrier against the outside world. The first step is to stop bleeding, says Khalia Primer, a PhD candidate at the South Australian Health and Medical Research Institute (SAHMRI).

During this haemostasis phase, blood vessels constrict to limit blood loss, she says. ‘Platelets also come along and clog up any vessels that are still bleeding.’

The next main phase is inflammation; the wound feels hot and is reddish around the edges. Blood vessels dilate, become ‘leaky’ and attract and admit immune cells — the body’s roving defenders and clean-up crew — to the wound.

‘White blood cells flock to the area and clear out all the bacteria that might have got in,’ Primer says. They, along with other cells, secrete growth factors to help initiate the next step: proliferation.

At this point, cells called fibroblasts move into the wound and quickly lay down collagen, providing scaffolding for functional tissue and structures such as blood vessels. Stimulated by vascular endothelial growth factor, new capillaries growing into the wound provide much-needed oxygen and nutrients to the new tissue and whisk waste away.

Finally, the maturation or remodelling phase refines the now-closed wound. Collagen fibres haphazardly deposited by fibroblasts are realigned, increasing the scar’s strength, and excess blood vessels pruned. ‘There’s a lot of coordinated apoptosis (programmed cell death) of unneeded cells at this stage,’ Primer says.

Healing, interrupted

Routine healing culminates in scar tissue which can, over time, fade. But disrupt any of these steps, and chronic wounds or ulcers develop.

Some people are more susceptible to skin ulcers. As years roll by, our skin tears more easily, and poor circulation becomes common. These and other age-related changes mean otherwise minor wounds can become chronic.

A raft of diseases can hamper skin repair in different ways too. In some immune disorders, for example, fewer white blood cells are available to tidy up the wound site and regulate inflammation.

Elevated blood sugar in diabetes wreaks havoc on cells involved in wound repair, Primer points out. For instance, immune responses, fibroblast actions and blood vessel growth processes all malfunction in the presence of persistent hyperglycaemia. ‘And once a person with diabetes gets a chronic wound, there’s a decent chance that at some point, they’re going to need an amputation.’

Wound care advances

Alongside the pain and physical and emotional toll they inflict, chronic wounds are estimated to cost the Australian healthcare system $3 billion each year. With an ageing population and ever-higher incidence of diabetes, these costs are forecast to increase too.

Current clinical practice is to regularly change dressings to check for redness and swelling, but this can be painful and damage the fragile wound surface.

Burn treatment was improved by ‘spray-on skin’ developed in the 1990s by Prof Fiona Wood and Marie Stoner. This alternative to traditional skin grafts harvests small samples of skin cells from a patient, cultures them in as little as 30 minutes and sprays them onto the wound.

Regenerative medicine, which harnesses the self-renewing abilities of stem cells, has also seen significant advances in the past couple of decades. One benefit regeneration has over repair is the ability to restore more functional tissue with less scarring. Stem cells can produce a range of cell types, so may one day help regain skin pigmentation, hair follicles and sweat glands — things standard wound repair cannot do. But these promising techniques must still clear safety, regulatory and cost hurdles before they’re widely used.

To help wounds heal faster, researchers at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) are developing treatment and monitoring technologies. They include:

Better bandages. Dr Asma Khalid, a CNBP Associate Investigator at RMIT University, takes liquid silk, mixes it with diamond particles and creates membranes that can be used as ‘smart’ dressings that monitor early signs of infection. Silk provides structural support to the wound bed and promotes skin regrowth. It’s also biodegradable, and can dissolve in the body without eliciting an immune response.

Targeted drug delivery. Dr Khalid’s liquid silk technique means she can add any water-based drug and antibacterial agents to her bandages for localised delivery. ‘We can also control the degradability of the silk structure,’ she says. ‘We can make it degrade quickly, so it delivers the drug and disappears within a few days, or not degrade at all and remove it once the wound’s fragile surface is healing.’

Temperature and pH monitoring. Dr Khalid and Patrick Capon from the University of Adelaide are combining silk films with particles to wound monitor temperature and pH — two indicators for how well the tissue beneath is healing. ‘A high temperature can signal infection, while if it’s too acidic or basic, it means the wound is not healing well,’ Dr Khalid says.

Dr Khalid is also working with CNBP Prof Brant Gibson, also at RMIT University, and SAHMRI’s Dr Christina Bursill to develop a smart wound dressing and portable detection system that tracks fluorescence from these sensors.

Metabolism monitoring. In glucose disorders such as diabetes, some cells crucial to wound healing ramp up their metabolic rate while others dial it down. The CNBP’s Dr Roman Kostecki and Prof Andrew Abell at the University of Adelaide are refining techniques that can measure metabolic by-products and track wound healing progression.

‘Window’ into the wound. The University of Adelaide’s Bioengineering Imaging Group, headed by Prof Rob McLaughlin, is working with Dr Khalid to ‘see’ layers below the skin’s surface. The technology, optical coherence tomography, tracks blood vessels as they regrow — another indicator of healing.