O envolvimento dos macrófagos nos efeitos da suplementação com ácidos graxos ômega-3 sobre a cicatrização de feridas: da bancada para o leito do paciente

Resumo

Defective wound healing is a common complication of ageing, diabetes and obesity and a strong relationship between malnutrition, poor wound healing and infection exists. Omega-3 fatty acids are fish oil derivatives associated with maintenance of optimum immune responses, since it activate cells of the innate immune system called macrophages. Macrophages orchestrate wound healing by fighting invading pathogens; recruiting endothelial cells and fibroblasts to damaged areas for tissue repair, and eliminating dying cells and debris. Despite strong experimental evidence behind omega-3 benefits, there is no formal demonstration that peri-operative (when the nutritional support initiates before surgery and lasts days or months after it) omega-3 supplementation improves recovery. The aim of this multi-species project is to determine if peri-operative omega-3 fatty acids improve wound healing and prevent post-operative infection. The human study includes a clinical trial sponsored by Royal Surrey County Hospital NHS Foundation Trust where surgery patients will receive peri-operative omega-3 supplements. Blood cells, serum and peritoneal cells will be collected and characterised using cytokine measurement, CYTOF, ImageStream analysis, and whole cell lipidomics. In mice, bone marrow transplantation and macrophage depletion will clarify how omega-3 affect specifically macrophage functions. Parallel human/murine organoid assays will corroborate the role of omega- 3 on macrophages functions during wound healing in alignment with NC3Rs priorities. We expect to clarify the mechanisms involved in the peri-operative omega- 3 fatty acid effects on tissue repair and will have direct repercussion on patient management worldwide. (AU)