Fish Skin Grafts Affect Adenosine and Methionine Metabolism during Burn Wound Healing

Burn wound healing is a complex process orchestrated through successive biochemical events that span from weeks to months depending on the depth of the wound. Here, we report an untargeted metabolomics discovery approach to capture metabolic changes during the healing of deep partial-thickness (DPT) and full-thickness (FT) burn wounds in a porcine burn wound model. The metabolic changes during healing could be described with six and seven distinct metabolic trajectories for DPT and FT wounds, respectively. Arginine and histidine metabolism were the most affected metabolic pathways during healing, irrespective of burn depth. Metabolic proxies for oxidative stress were different in the wound types, reaching maximum levels at day 14 in DPT burns but at day 7 in FT burns. We examined how acellular fish skin graft (AFSG) influences the wound metabolome compared to other standard-or-care burn wound treatments. We identified changes in metabolites within the methionine salvage pathway, specifically in DPT burn wounds that is novel to the understanding of the wound healing process. Furthermore, we found that AFSGs boost glutamate and adenosine in wounds that is of relevance given the importance of purinergic signaling in regulating oxidative stress and wound healing. Collectively, these results serve to define biomarkers of burn wound healing. These results conclusively contribute to the understanding of the multifactorial mechanism of the action of AFSG that has traditionally been attributed to its structural properties and omega-3 fatty acid content.