Every week the Biochemistry department at Sussex holds a seminar session with guest speakers open to all. Whether they are captivating or go way over my head, it’s always interesting to hear about research being done in a completely different area of science and particularly nice when they grab my attention. A couple weeks back, the seminar was hosted by one of my favourite lecturers, Dr Louise Serpell, so I thought I’d head over. And was very pleasantly surprised.
Her guest speaker, Dr Toby Jenkins, is currently undergoing research into creating better dressings in the prevention of infection for burn victims. And he has some intriguing findings. Jenkins and his lab focus mainly on paediatric burn victims (children). Accidents like a spilt cup of tea can mean horrible scars and even death in young children and they happen all the time. As infants have a different biochemistry to adults and different pharmacological needs and responses, they are also of particular interest clinically.
For instance, children are at particular risk of infection following burns, with a high incidence of Toxic Shock Syndrome (TSS). TSS can be fatal if undiagnosed. The main culprit is a superantigen toxin called TSST-1 (TSS toxin-1). A normal antigen, after cellular uptake, will bind with a specific MHC molecule and be recognised by a specific type of T cell. T cells are a king of white blood cell which kicks in the body’s immune response. It is called a supernatigen as it has no T cell specificity. It will thus induce an over activation of T cells, which can ultimately lead to death if untreated.
Burn wounds can be classified into superficial, partial thickness and full thickness. The most common of which in children is partial thickness and can often be treated without surgery.
But often, skin grafts are necessary to achieve healing. This is when “smart dressings” come in. Conventionally, normal non-adherent dressings were used. But these are very prone to infection, especially as they have to be removed and replaced often. Some new specialised dressings – termed biological dressings – have come onto the market recently. Biologically-derived dressing BiobraneTM is state of the art and focuses on encouraging epithelial growth and preventing infection. It is made from collagen-coated nylon and packed with growth factors that create an ideal environment for tissue regrowth. It has been very effective and its results bode well for the future, being used in many specialist burn centres.
The trouble is that these dressings don’t detect or heal burn wound infection. The only way to find out if a child has an infection is either to remove the dressings – which could lead to greater infection – or clinically diagnose it – by which time the child is already in a critical state. What’s more, many of the growth factors that encourage skin growth are also likely to encourage microbial growth. This is where Jenkins comes in. His team are working hard on creating a biological dressing that both generates a positive environment for skin cells to grow, but also detects and treats infection. The idea is that the dressing could contain a colour marker, which would alert clinicians to an infection and release antimicrobials to deal with the infection.
But how would it work? The design is based on the generalisation that most toxins contain enzymes that attack cell membranes. Cell membranes are formed of a double layer of phospholipids which are degraded by these enzymes. Another cellular components composed of a double layer of phospholipids are vesicles. They are used in cellular processes to carry molecules from one area of the cell to another, or from one cell to another. It is possible to synthetically create vesicles; a number of drug delivery systems work in the same way. The drugs are in vesicles which then get degraded in our stomachs. Jenkins has focused his research on synthesising a vesicle which would contain an antimicrobial as well as a dye which changes colour. The enzymes from toxins which would attack the cell membranes would also attack the vesicles in the dressing. They would then release the dye and the antimicrobial substances to both treat and diagnose the infection.
Although the research for the right dyes and antimicrobials is still in its early days, the work has already ruled out some key candidates, like silver. Nanoparticles of silver are very in at the moment but they have a high toxicity risk, especially at the concentrations needed for them to be effective in fighting bacteria.
It is also important that the created vesicles only respond to pathogenic bacteria and not harmless bacteria which are important in the normal defence against infection. The Jenkins lab do not see their product being on the market before 2015 – as there is still a lot of research to be done – but they have proven the importance and significance of their research with the many children’s lives they have already helped to save.
