Phases of Wound Repair

Hemostasis is the first phase of wound repair, occurring immediately after injury. Damaged blood vessels constrict to reduce blood flow and create hypoxia at the wound site. This attracts platelets and activates the clotting mechanism, forming a blood clot that seals the wound and prevents infection and further bleeding.

During the inflammation phase, neutrophils and macrophages are recruited to the injury site through the bloodstream. Neutrophils kill bacteria by releasing proteolytic enzymes, while macrophages secrete cytokines and growth factors like interleukin and tumor necrosis factor. Both cell types promote fibroblast proliferation and angiogenesis, advancing the healing cascade.

Collagen is the major fibrous protein in the extracellular matrix that provides tensile strength. During proliferation, fibroblasts secrete type III collagen, which is weaker. In the remodeling phase, matrix metalloproteinases convert type III collagen into type I collagen, a stronger protein. Type I collagen is arranged into parallel bundles to provide rigidity and strength to newly formed tissues.

Granulation tissue forms during the proliferation phase when fibroblasts migrate from surrounding tissue, divide, and secrete a collagen-rich extracellular matrix. These cells also promote reestablishment of the blood vessel network. The granulation tissue gradually transforms into scar tissue during remodeling, mimicking normal tissue structure and completing the healing process.

When blood vessels are damaged, vasoconstriction reduces blood flow to the injury site, creating hypoxia or oxygen deprivation. This hypoxia causes surrounding cells and tissues to shift ATP production to anaerobic glycolysis, producing lactic acid that lowers pH. The reduced oxygen and pH changes significantly induce platelet activation, adhesion, and aggregation to form a blood clot.

During remodeling, the wound contracts and most fibroblasts die. Collagen fibers are rearranged into an organized, rigid structure that provides strength to newly formed tissues. Matrix metalloproteinases remodel the extracellular matrix, transforming granulation tissue into scar tissue that closely resembles normal tissue structure and completes the healing cascade.

The blood clot serves multiple critical functions in wound repair. It seals the injury site from external infection and establishes a temporary matrix composed of thrombin, collagen, fibronectin, and platelets. This matrix induces several cytokines and growth factors needed during the repair process, making it essential for initiating the subsequent phases of healing and supporting regeneration and repair.