A wound is a loss of the normal integrity of skin and underlying soft tissue leading to a devitalized structure. Wounds can result from skin injury in case of surgery, puncture wounds and abrasions or can be secondary to skin necrosis as a result of ischemia or pressure. People with diabetes mellitus, peripheral ischemia, venous stasis, infection and bad nutritional status are vulnerable to wounds with easy skin disruption and difficult healing process that may lead to chronic ulcer. The process of wound healing occurs to protect the underlying structures from any infection or blood loss. Wound healing occurs through several physiological stages in healthy individuals that include hemostasis, inflammation, epithelialization (granulation) or proliferation and finally fibroplasia or remodeling.

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wound on palm of hand

Image: “Wound on palm of hand a day after falling off a bike onto concrete.” by Arria Belli – Own work. License: Public Domain

Pathophysiology and Stages of Wound Repair


Hemostasis starts with vasoconstriction of the blood vessel and a platelet plug that activates more platelets. The intrinsic and extrinsic clotting cascade is activated by the platelets and the damaged tissue to form fibrin mesh with platelets, WBCs and RBCs.

Activated platelets release growth factors and cytokines including platelet-derived growth factor and transforming growth factor beta to help with cellular proliferation and granulation. This is an immediate stage following the injury.


Inflammation comes next in order to clear the dead cells, bacteria and cellular debris with phagocytes and inflammatory cells. Growth factors are released from these cells to facilitate migration and proliferation of cells to allow tissue regeneration.

Neutrophils migrate from the circulation to the intercellular space within hours guided by the complement system and cytokines. Monocytes leave the circulation to become macrophages, which are responsible for more wound cleaning from dead cells and debris within the first few days after injury.

Cytokines, tumor necrosis factor (TNF), interlukin-1 and PDGF are all secreted by macrophages to facilitate growth of fibroblasts, myofibroblasts, smooth muscles cells, epithelial cells and endothelial cells. This stage lasts for a few days from the injury with neutrophils acting in 3 days and macrophages in the first week.

Granulation stage

Granulation tissue consists mainly of new blood vessels, connective tissue and collagen. Collagen in the wound is mainly of the type III that converts to type I collagen. Fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) promote angiogenesis and cellular proliferation.

Angiogenesis is the formation of basement membrane with migration and proliferation of endothelial cells to form new capillaries surrounded by myofibroblasts. Fibroblasts divide and promote contraction of the wound edges to facilitate epithelialization from the periphery to the center. This stage can last for few weeks.


Remodeling follows with apoptosis of the excess cells and degradation and alignment of the collagen fibers with skin tension lines. This phase can last for years after the initial injury.

Factors Affecting Wound Healing

There are several factors which delay wound healing leading to chronic ulcer or scar formation. These factors include systemic factors and local factors in the wound.

Systemic factors are diabetes mellitus, vascular and connective tissue diseases, age, nutritional deficiency, smoking and alcohol.

Local causes that impair wound healing include presence of foreign bodies within the wound, infection, edema and moisture.

Types of Wound Healing

There are 3 different types of wound healing: primary closure, delayed primary closure and secondary closure. However, the mechanism of all three of them is similar to each other.

Primary closure or intention occurs with paper cut wounds and surgical incisions where there is a small defect with little risk of complications and infection.

Secondary closure occurs when there is a gap or tissue defect in large wounds and the edges cannot close with primary intention e.g. lacerations, burns and ulcers. Granulation tissue with new blood vessels and collagen is needed to close the defect or the skin loss leading to a scar formation. This type of wound healing poses a risk of infection and it needs longer time to close.

Delayed primary closure or tertiary intention occurs mainly in wounds that need to be left open to ensure that there was no contamination with organisms, then the wound is surgically closed. The wound is watched open for a few days and then closed surgically to heal with both primary and secondary intention. Examples of such wounds are dog bites, wounds including foreign bodies and wounds healing by a tissue graft.

Complications of Wound Healing

Wound healing can result in hypertrophic scar or keloid that is raised above the skin due to proliferation of fibroblasts. Keloid is different in that it extends beyond the border of the wound site with irregular dense collagen fibers and usually painful. Keloid is not common in white race.

Hypotrophic or atrophic scar occurs as a depression in the wound site due to scanty collagen in case of acne and some viral infections. Rapid healing of the wound will affect the scar size. The more rapid healing is, the less will the size of the scar be.

Long-term complications include hypo- or hyperpigmentation, calcification and incisional hernia.

Other complications include excess contracture as in burns, and wound dehiscence due to defective granulation.

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