Wound Healing Stages

Wound; trauma or damage to the tissue due to surgical causes resulting in loss of anatomical and functional integrity. Wound healing occurs through a series of sequential cellular and biochemical events that restructure the tissue. Wound healing is a biological process involving a sequence of multiple cellular activities dynamic. This biological process occurs in four stages: “hemostasis, inflammation, proliferation and remodeling”.

Hemostasis

This phase begins immediately after wound formation and includes the body’s initial physiological responses aimed at stopping bleeding. In the first stage, the damaged vessel wall contracts due to trauma, reducing blood loss. Meanwhile, platelets activated by exposed collagen and microfibrils at the wound site adhere to each other and to the vessel wall, forming a temporary platelet plug. Subsequently, this temporary plug is stabilized by fibrin formation, leading to the development of a permanent clot. The blood clot and platelets also form a temporary matrix to facilitate the migration of macrophages, endothelial cells and fibroblasts. Platelet alpha granules released upon platelet adhesion to each other and to the vessel wall contain platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-beta), and serotonin, which trigger the release of wound-activating substances. This release attracts macrophages, endothelial cells, and fibroblasts to the wound area.

Inflammation

The primary objective of inflammation is to recruit inflammatory cells to the wound site and sustain inflammatory activity. This phase is divided into early and late inflammatory phases.

Early Inflammatory Phase: In this phase, neutrophils secrete proteolytic enzymes such as IL-1 alpha, IL-1 beta, and TNF-alpha, which break down foreign particles and bacteria through phagocytosis and remove them from the environment. Thus, damaged extracellular matrix components and dead tissue are cleared. The proteolytic secretions of neutrophils also serve as activators for growth factors subsequently released by macrophages, keratinocytes, and fibroblasts in later stages importance.

Late Inflammatory Phase: In this phase, macrophages play an active role and phagocytosis continues. Macrophages contribute to wound healing by secreting numerous cytokines and growth factors that influence cellular and biochemical processes. In the final stage of this phase, lymphocytes are recruited to the wound site under the influence of interleukin-1 (IL-1). IL-1 plays a critical supply in regulating the enzyme collagenase, which is essential for many cellular activities.

Proliferation

This is the stage during which granulation tissue, a prerequisite for wound healing, forms. In this phase, fibroblasts and endothelial cells are highly active. Fibroblasts are key mesenchymal cells that play both a structural and mechanical role in wound healing. They produce Collagen fibers, thereby providing tensile strength and resistance to the wound area. Epithelialization begins in the first stage. In areas of extensive tissue damage and loss, regeneration starts from the wound edges. Subsequently, epithelial cells migrate over the granulation tissue. Migration continues until opposing epithelial edges meet. Contraction then occurs, reducing the size of the wound. The proliferative phase ends once granulation tissue has formed and epithelialization is complete. Endothelial cells play a vital role in angiogenesis, a key component of wound healing during this phase.

Remodeling

This is the final stage of wound healing, during which epithelium and scar tissue form. Granulation tissue is restructured to restore the tissue’s normal architecture, resulting in scar formation. In this phase, the extracellular matrix is subjected to maximum tensile stress. Through the breakdown and reorganization of collagen structure, the tissue is strengthened, leading to the formation of a scar with increased mechanical strength.