Developing a smart non-antibiotic cerium-containing biodegradable wound dressing for treating chronic ulcers

The treatment of long-term ulcers is becoming a major clinical problem, being currently the fourth biggest cost to the NHS in the UK. Persistent presence of bacteria in chronic ulcers involves repeated cycles of antibiotic treatment which can lead to antimicrobial resistance (AMR). Antibiotic resistance is becoming a global problem and there is a pressing need for the development of new approaches to reduce the volume of prescribed antibiotics. The design of non-antibiotic synthetic platforms has been identified as a rapidly evolving field; a good example is the use of silver. Although silver-based products have been relatively successful and have been proved to being able to kill microorganisms when used correctly, it has been reported that they can ultimately delay tissue healing. For example, some silver-based nanosystems have been found to lead to apoptosis pathways. Other alternatives include the use of cerium-based derivatives, for example, cerium nitrate, which has been used in burn wounds management (in combination with silver sulphadiazine) since 1976 and it has been recently reported as a potential novel biofilm inhibitor.
An additional issue with currently used wound dressings is that they tend to be inflexible in nature and cover the wound surface without packing into contoured wounds, therefore, bacteria can inevitably escape. Wound dressing removal and re-application can also be painful for the patient and, in these cases, the use of biodegradable membranes which would degrade within the infected wound would be of great benefit.

An ideal wound dressing would therefore be multifunctional and contain a non-antibiotic antibacterial mechanism and an anti-inflammatory/pain relieving agent. It should also be flexible enough to pack into contoured wounds and biodegradable.
The aim of this project is to create a new bi-layered construct to be used as a wound dressing in the treatment of chronic infected wounds. This construct will be flexible and biodegradable and it will be manufactured using FDA approved polymers and electrospinning. The bi-layered scaffold will be multifunctional: (i) Layer 1 will include an anti-inflammatory agent; (ii) Layer 2 will include an antibacterial component (cerium derivative).The student undertaking this project will be expected to develop and characterise the bi-layered scaffold and then test its antibacterial activity using clinically relevant bacterial species (e.g. Pseudomonsa aeruginosa and Staphylococcus aureus) both in 2D models and in 3D tissue engineered models of skin wound infection. The project will be developed in a multidisciplinary environment working at The School of Dentistry with Dr. Ilida Ortega (expert in Biomaterials) and Dr. Joey Shepherd (expert in Microbiology).