Targeting Extracellular Matrix Remodelling in Cutaneous Wounds to Promote Better Healing

Wound healing is a physiological process leading to the restoration of the skin barrier integrity after injury. A large number of factors (wound size and location, exogenous pathogenic agents, aging, co-morbidities, genetic diseases) can affect wound healing and prevent its normal resolution, leading to wounds that never heal (i.e. chronic wounds) or that heal in an aberrant manner (e.g. with scarring or dermonecrosis). Wound healing disorders affect up to 6% of the adult population in the world and this number is expected to continue to grow due to population aging and increasing incidence of metabolic diseases. In addition, current therapeutic solutions lack efficiency and there is an urgent need for better diagnostic tools to improve wound management. In the REMOD-HEALING project, we propose to tackle the burden of pathological wounds by exploiting the huge reservoir of therapeutic targets and biomarkers associated with extracellular matrix (ECM) remodelling in cutaneous wounds. Our innovative approach will be to analyse, model and target the aberrant ECM modifications induced by proteolytic enzymes in various healing disorders (chronic ulcers, epidermolysis bullosa, snake bite-induced dermonecrosis) with the hypothesis that the quality of the ECM shaped by proteases dictates the quality of tissue regeneration. We have gathered a team of 14 European and Latin American partners to provide excellent training to 12 doctoral candidates and generate breakthrough research allowing us to (i) gain a deeper understanding of proteolytic networks in normal and pathological wounds in order to identify novel potential biomarkers and protease targets (Objective 1), (ii) obtain biochemical and structural information on specific protease targets, their ECM substrates and their endogenous inhibitors to fuel the discovery of diagnostic tools and anti-protease drugs (Objective 2), (iii) develop new diagnostic and therapeutic tools to improve wound management (Objective 3).