Wound healing is a complex process taken up by the body to repair the defect by restoring cellular structure and tissue layers.
Wound healing process has distinct phases which are
- Hemostasis
- Inflammatory Phase
- Proliferative or Granulation Phase
- Remodeling Phase
Hemostasis
Some authors consider this a separate entity and do not include in phases of wound healing. Anyway, hemostasis is series of events that aims to minimize the bleeding.
Before actual inflammatory phase begins, there occurs an event called clotting cascade, which helps to minimize bleeding and generate factors for actual inflammatory phase.
Clotting cascade is initiated when blood comes in contact with collagen. This triggers blood platelets to secreting inflammatory factors. Platelets stick to each other to form an aggregate.
Fibrin and fibronectin cross-link together and form a plug that traps proteins and particles to prevent further blood loss and offer structural support for the wound. Platelets adhere to it and secrete a number of factors into the blood which includes extracellular matrix proteins, cytokines, and growth factors.
Other proinflammatory factors like serotonin, bradykinin, prostaglandins, prostacyclins, thromboxane, and histamine are also released by the platelets. These increase cell proliferation, causes other cells to migrate to the area and dilate the vessels.
Inflammatory Phase
Ruptured cell membranes, immediately on getting injured release inflammatory factors like thromboxanes and prostaglandins causing blood vessels to constrict and prevent blood loss.
This vasoconstriction lasts five to ten minutes and is followed by vasodilation which peaks about 20 minutes after injury [widening of blood vessels].
Vasodilation is the result of factors like histamine, which also causes porosity of the vessels and leakage of proteins from the bloodstream into the extravascular space and the entry of inflammatory cells like leukocytes into the wound site.
Within an hour of wounding, polymorphonuclear neutrophils arrive at the wound site phagocytize debris and bacteria. They also kill bacteria by releasing free radicals.
T cells, other types of leukocytes enter the area and secrete cytokines. These cytokines cause further T cell division, increase inflammation, enhance vasodilation and vessel permeability.
T cells also increase the activity of macrophages. Macrophages replace polymorphonuclear cells in the wound by two days after injury. Macrophages are mature monocytes which are attracted to wound sites by growth factors released by platelets.
Macrophages phagocytize bacteria and damaged tissue and they also debride damaged tissue by releasing proteases.
Macrophages also secrete growth factors and cytokines, which attract cells involved in the proliferation stage of healing to the area.
With the passage of time, fewer inflammatory factors are secreted and numbers of neutrophils and macrophages are decreased at the wound site indicating the end of the inflammatory phase.
Proliferative or Granulation Phase
For ease of sequencing and understanding, the proliferative phase has been divided into different subphases, which occur in the continuation and overlapping manner.
The subphases are
- Fibroplasia
- Matrix deposition
- Angiogenesis
- Re-epithelialization
In days 5-7, fibroblasts have migrated into the wound, lay down new collagen of the subtypes I and III.
The fibroblasts produce glycosaminoglycans and fibronectin including heparan sulfate, hyaluronic acid, chondroitin sulfate, and keratan sulfate. These lead to matrix deposition.
Angiogenesis is the formation of new blood vessels which is regulated by basic fibroblast growth factor and vascular endothelial growth factor.
Migration and division of peripheral cells occur in hours 48-72, resulting in a thin epithelial cell layer, which bridges the wound. This process is called reepithelialization.
This proliferative phase lasts about 4 weeks.
Remodeling
Remodeling commences around the third week and leads to changes in wound structure and strength by replacing the type of collagen present in the wound to match the that in normal tissue.
Specialized fibroblasts termed myofibroblasts also lead to wound contraction, which results in movement of the edges of a wound towards the center to close it.
Types of Wound Healing
Primary Healing
This type of healing occurs when the wound edges are brought together/ approximated. There is minimal scarring in this case.
Most surgical wounds heal by primary intention healing.
Delayed Primary Healing
This type of wound healing occurs when the wound is initially cleaned, debrided, and observed, typically 4 or 5 days before closure. Many wounds which are initially contaminated are purposely left open and a delayed closure is done.
Healing By Secondary Intention
In this type of healing, a full-thickness wound is allowed to close and heal. Secondary healing results in an inflammatory response that is more intense than with primary wound healing. A larger amount of granulation tissue is formed and there is a greater contraction. This kind of healing leads to larger scars.
Healing by Epithelization
Epithelization is a part of wound healing occurs in all kinds of wound healing as part of the phases of wound healing. It is the process by which epithelial cells migrate and replicate and traverse the wound.
In wounds involving only the epidermis and superficial dermis, epithelization is the predominant method by which healing occurs.
