Exploring the material benefits of wound healing
A wound to the skin is a threat to the body. Apart from the physical pain, it gives microbes and viruses a portal to set up infection that, in severe cases, could result in the loss of life or limb.
Normally the body has a finely-tuned mechanism for protecting against wounds in the first place and healing them quickly when they happen. But what if those systems break down? What if skin becomes wounded at the slightest touch? And what if wounds that form fester rather than heal?
Professor Wenxin Wang is developing new biomaterials to support the skin’s protective and wound healing processes, and he is designing them with particular diseases in mind. One is Epidermolysis Bullosa (EB) where wounds arise at the slightest touch, overwhelming the skin’s defences, and the other is diabetes, where wounds on the feet and legs can become chronic, sometimes resulting in the need to amputate.
“Generally my group’s research looks at wound healing,” says Dr Wang, who is Senior Lecturer in Skin Research and Wound Healing at UCD School of Medicine and Medical Science. “And to do this we are developing next-generation multi-functional biomaterials for applications in wound healing.”
A chemist by training, Dr Wang initially carved out a research career as a polymer engineer, but in 2007, when he discovered a new method to build branched polymers, he switched from more chemistry-oriented research to health and medical research. In 2013 he took up a Principal Investigator position at the Charles Institute in University College Dublin.
Using synthetic chemistry, Dr Wang is now making new biomaterials that deliver protective or restorative agents to the skin and help wounds heal before the damage gets too severe.
His group designs and builds polymers with a variety of defined shapes: some are hyperbranched, some are ‘dendritic’ or tree-shaped and some form knotted structures. These polymer designs can be specifically tailored to suit the needs of the particular disease being addressed, explains Dr Wang.
“We look at the disease, we think about the disease and what the skin needs, and then we design our polymer according to those needs,” he says. “The chemical structure gives the material a certain function, then we can include different therapeutic agents or signals in the polymer to have an effect on the skin.”
EB - the ‘butterfly skin’ disease
A major focus of Dr Wang’s research is on the condition EB, where the skin can be damaged by light pressure or friction, causing pain, blisters, wounds and the potential for infection. Around 500,000 people globally are thought to be affected by EB, and there is currently no cure.
In a form of the condition known as Recessive Dystrophic Epidermolysis Bullosa, or RDEB, the skin lacks a structural protein called collagen VII, which normally anchors the top layers of skin (the epidermis) to the lower layers (the dermis). Without collagen VII to hold the epidermis in place, it can be easily blistered or even removed.
Dr Wang wants to use his lab’s biomaterials to deliver a therapeutic gene, COL7A1, into specific skin cells so they can produce collagen VII, and so far the results look promising.
“We have shown that our polymer can carry the COL7A1 gene into these skin cells (keratinocytes and fibroblasts) growing in the lab, and the cells then use the gene to make collagen VII,” he says.
The results with cells growing in the lab has given the group confidence to deliver the genes in vivo in experimental mouse models. PhD student Lara Cutlar has been analysing the results, and has found that the polymer and COL7A1 gene are together triggering collagen VII production in the target cells.
Dr Wang, who is already the Founder, Chairman and CSO of biomaterials company Vornia, is now considering commercialisation routes to help bring these discoveries closer to the clinic.
“We are very excited about these results because we are seeing that injecting the polymer and the COL7A1 gene into the skin results in collagen VII being formed,” he says. “Now we want to look more at the safety so we can move to clinical trials, and to develop a topical application based on our polymer, to make it easier to deliver the gene to the cells that need it.”
Halting the march of diabetic wounds
Another target group of patients in Dr Wang’s sights is people with diabetes. Over time, diabetes can damage the nerves and circulation of the lower limbs, and if wounds form they can become a serious problem. “These wounds are very heard to heal, and in severe cases the person may need an amputation,” he explains.
Again, Dr Wang’s group has been looking at the specific needs of diabetic wounds and has developed a tailored biomaterial that could be used in dressings. “It can be used to carry therapeutic agents such as stem cells and growth factors,” he says.
One of the benefits of the specially-designed biomaterial is that it can be applied directly to the wound, where the chemical and thermal environment prompt it to form a soft hydrogel, and Dr Wang’s group is now exploring the proposition of putting fat-derived stem cells and other agents to promote healing into the mix, so it alters the wound environment and promotes healing.
With funding from a variety of sources, including DEBRA Ireland and DEBRA International, Science Foundation Ireland, the Health Research Board of Ireland, Enterprise Ireland, Irish Research Council, University College Dublin and the European Union (under Framework Programme 7 and Horizon 2020), Dr Wang says his ultimate goal is to help patients.
“When I meet patients, and particularly patients with EB, I feel I have a responsibility to do something to help them, this is my motivation,” he says. “I always say to my students and my postdocs in the lab, we need to really work hard, to do something for people with EB and for people with diabetes. That is what keeps driving us.”