Resolution of Inflammation in Wound Healing: Basic Best Practice and Synergistic Therapy

Introduction: Inflammation is a complex physiological process that serves as a protective response to infection, tissue injury, or stress. This response involves the recruitment of leukocytes, hyperemia, and increased vascular permeability, leading to the accumulation of fluid in the affected tissues. Local edema decreases tissue perfusion and amplifies recruitment and activation of immune cells, particularly neutrophils, increasing collateral tissue damage and inflammation. Prolonged inflammation leads to tissue fibrosis and is a prominent factor in many chronic conditions. Two important factors in the resolution of inflammation are lymphatic function and tissue oxygenation. The lymphatic system plays a crucial role by clearing inflammatory cells, debris, and cytokines from injured tissues, maintaining tissue fluid homeostasis, and regulating the immune response. Edema is indicative of lymphatic overload, therefore it must be managed for effective resolution of inflammation, regardless of wound etiology. Oxygen is essential for many wound healing processes, including inflammation resolution. Oxygen modulates the immune response by influencing the activity of neutrophils, macrophages and lymphocytes and is necessary for the synthesis and function of reactive oxygen species (ROS) and specialized pro-resolving lipid mediators critical for inflammation resolution.Hypoxia, inflammation and dysregulated lymphatic function (edema) are characteristic of most chronic wounds. Interventions that support the lymphatics and improve tissue oxygenation work synergistically to resolve inflammation and promote wound healing.Methods:A review of relevant literature and illustration of the mechanisms involved will be presented.Results:Strategies for supporting the lymphatics and improving wound bed oxygenation will be discussed.Discussion: References:Cui, K., Wu, H., Li, K. S., Peng, Q., Wang, D., Cowan, D. B., … & Chen, H. (2023). Promoting lymphangiogenesis and lymphatic growth and remodeling to treat cardiovascular and metabolic diseases. Arteriosclerosis, Thrombosis, and Vascular Biology, 43(1). https://doi.org/10.1161/atvbaha.122.318406 Wu, C., Li, H., Zhang, P., Tian, C., Luo, J., Zhang, W., … & Yu, H. (2020). Lymphatic flow: a potential target in sepsis-associated acute lung injury. Journal of Inflammation Research, Volume 13, 961-968. https://doi.org/10.2147/jir.s284090 Ocansey, D. K. W., Pei, B., Xu, X., Zhang, L., Olovo, C. V., & Mao, F. (2021). Cellular and molecular mediators of lymphangiogenesis in inflammatory bowel disease. Journal of Translational Medicine, 19(1). https://doi.org/10.1186/s12967-021-02922-2 Park, J., Langmead, C. J., & Riddy, D. (2020). New advances in targeting the resolution of inflammation: implications for specialized pro-resolving mediator gpcr drug discovery. ACS Pharmacology &Amp; Translational Science, 3(1), 88-106. https://doi.org/10.1021/acsptsci.9b00075 Schwartz, N., Chalasani, M. L. S., Li, T. M., Feng, Z., Shipman, W., & Lu, T. (2019). Lymphatic function in autoimmune diseases. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.00519 Molon, S., Brun, P., Scarpa, M., Bizzotto, D., Zuccolotto, G., Scarpa, M., … & Bonaldo, P. (2023). Collagen vi promotes recovery from colitis by inducing lymphangiogenesis and drainage of inflammatory cells. The Journal of Pathology, 260(4), 417-430. https://doi.org/10.1002/path.6092 Ahmed, S. R., Mostafa, E. M., Musa, A., Rateb, E. E., Al-Sanea, M. M., Abu-Baih, D. H., … & Abdelmohsen, U. R. (2022). Wound healing and antioxidant properties of launaea procumbens supported by metabolomic profiling and molecular docking. Antioxidants, 11(11), 2258. https://doi.org/10.3390/antiox11112258 Miricescu, D., Bădoiu, S. C., Stănescu-Spînu, I., Totan, A. R., Ştefani, C., & Greabu, M. (2021). Growth factors, reactive oxygen species, and metformin—promoters of the wound healing process in burns?. International Journal of Molecular Sciences, 22(17), 9512. https://doi.org/10.3390/ijms22179512