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How Inflammation Affects Wound Healing

An injury to the human body initiates a wound healing chain reaction that occurs in four sequential ...

An injury to the human body initiates a wound healing chain reaction that occurs in four sequential but overlapping phases: hemostasis, inflammatory, proliferative and maturation. This post focuses on the second (inflammatory) phase, which begins after blood flow stops (i.e., hemostasis) and defender white blood cells, or leukocytes, migrate to the site of the injury — a process known as chemotaxis.1

Understanding the Inflammatory Stage of Wound Healing

The inflammatory stage typically lasts several days, but it can go on for much longer, making the wound chronic. Many cells and chemical reactions or signals keep the wound progressing in the inflammatory phase. Understanding these processes can jump-start a chronically stalled wound so that healing resumes.
The clinician’s goals in the inflammatory phase are to limit further damage, close the wound, remove cellular debris and bacteria, and encourage cellular migration.1 Following hemostasis and chemotaxis, white blood cells and thrombocytes release more mediators and signaling cytokines, which accelerates the inflammatory process. Several growth factors work in concert to promote collagen degradation, transform fibroblasts, grow new blood vessels and work toward re-epithelialization. Platelets release mediators, including serotonin and histamine, to increase cellular permeability.1 Fibroblasts are recruited and multiplied by platelet-derived growth factors. Once the fibroblasts are in place, they produce collagen, a crucial protein the body needs for building and remodeling.
During this process, a fibrin scaffold forms through platelet activation.1 
The scaffold gives the inflammatory cells a place to stick. Some of the inflammatory cells attracted to the scaffold are neutrophils, monocytes and endothelial cells.1

Neutrophils digest cellular debris and bacteria through a process called phagocytosis, which helps cleanse the wound. Monocytes fight infections and help remove dead or damaged tissues.2 Endothelial cells send signals to organize the growth of connective tissue cells that eventually form the surrounding layers of blood vessel walls.3All these cells working in concert keep the wound moving to the next healing phase, known as the proliferative or granulation phase.
Matrix metalloproteinases, or MMPs, are required for the migration of inflammatory cells. MMPs also break down proteins to allow new tissue to form. However, if MMP levels get too high or if MMPs are present for too long, they can break down proteins and growth factors and stall wound healing.4

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1. Basehore, B. M., Zito, P. M., & Wallace, H. A. (2020). Wound Healing Phases. Treasure Island, FL: StatPearls Publishing.
2. Territo, M. (2020, January). Monocyte Disorders. Retrieved from Merck Manuals.
3. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. & Walter, P. (2002). Molecular Biology of the Cell. New York: Garland Science.
4. Cullen, B., Gibson, D., Harding, K., Legerstee, R. & Shultz, G. (2009). MMPs Made Easy. Wounds International, 1(1), 1-6.

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