Translational Studies in Wound Healing

This work explores the role of gap junctional proteins (GJP) in wound healing in two clinical settings: venous disease and epidermal grafting. Chronic wounds and ulcers are common and a feared problem particularly in the elderly, causing pain and disability. Treatment costs are estimated at £2-3 billion to the NHS with a further loss of 2 million workdays per year. Varicose veins are the major contributor to the prevalence of ulcers affecting about 0.3-0.5% of the population at any point of time. The expression of GPJ; connexins 43, 30 and 26 were explored in a cross-sectional study of patients with varicose veins at different stages of venous disease (CEAP stage). A stepwise increase in GJPs overexpression was seen corresponding to the clinical CEAP stage of the disease, supporting their role in the disease mechanism and as a biomarker of wound healing. This is also the first-time varicose veins were shown to be associated with poor wound healing. Concurrently, with the introduction of a new wound healing system for epidermal grafting, a sequential program of research was developed. Initially, a systematic review using Cochrane methodology on epidermal grafting for wound healing, and a pilot case series to evaluate the novel surgical technology. Following positive outcomes; a patient reported outcome measure and cost evaluation study was performed. Combining these data, a pilot randomised controlled trial was performed to compare efficacy of epidermal grafting to standard of care. Alongside, translational studies on GJP were undertaken to outline the cellular mechanism of action of epidermal grafts. These data led to the development of a wound healing group at UCL and subsequent engagement with the MRC UCL clinical trials team to design a novel platform trial to further assess epidermal grafting. This platform will investigate the molecular mechanism of action and explore the most appropriate use for this technology. A NIHR EME and a collaborative industry grant is in progress