42.2: Phases of Wound Repair
Following injury, the integrity of the injured tissues must be reestablished. For example, in skin tissue, wound repair involves coordination among resident skin cells, blood mononuclear cells, extracellular matrix, growth factors, and cytokines to complete the healing cascade.
Formation of Blood Clot
In case of deep injuries, trauma to blood vessels results in blood loss. In the meantime, phospholipids released from the ruptured endothelial cellular membrane are converted into arachidonic acid and metabolites like thromboxane A2 and prostaglandin 2α. These factors promote vasoconstriction at the site of injury, generally lasting up to 5-10 minutes and resulting in brief hypoxia. Due to a lack of oxygen, cells and tissues surrounding the injury site shift ATP production via the anaerobic glycolysis pathway. The lactic acid produced at the end of anaerobic glycolysis reduces the pH in the adjoining tissues and cells. Blood vessel trauma and reduced pH significantly induce platelet activation, adhesion, and aggregation. Next, the blood clot is formed, sealing the injury site from external infection and establishing the temporary matrix composed of thrombin, collagen, fibronectin, and platelets. This matrix induces several cytokines and growth factors that are needed during the repair process.
Chemotaxis and Activation
Once the clot is formed, damaged cells at the injury site send a distress signal to immune cells in the body. This is followed by the recruitment of the neutrophils at the injury site. Prostaglandins E2 have a central role in the inflammatory response. They promote vasodilation and increase the blood flow to allow the movement of neutrophils. The neutrophils inhibit the growth of bacteria by releasing proteolytic enzymes. Even macrophages play a critical role in all the phases of wound repair, such as secretion of cytokines and growth factors like interleukin and tumor necrosis growth factor. They also promote fibroblast proliferation and angiogenesis at the wound site.
Extracellular Matrix Reorganization
Collagen is the major fibrous protein in the extracellular matrix (ECM) that imparts tensile strength and regulates cell adhesion to the tissues. The damage caused to ECM is restored in the remodeling phase of the wound repair. In the granulation tissue, ECM produced by fibroblasts is composed of type III collagen — a weaker structural protein. To cope with higher collagen demand, fibroblasts prefer to secrete type III collagen, and the rate of collagen production is highest. It is in the remodeling phase of the healing cascade that the matrix metalloproteinases (released by fibroblasts) remodel type III collagen into type I collagen that is stronger and has higher tensile strength. The arrangement of type I collagen into parallel bundles helps wound contraction and provides rigidity to newly formed tissues.
