Overview
Wound healing describes the process by which damaged skin is replaced by healthy, new tissue. Healing varies according to the wound type, however, they all follow broadly similar steps. The wound healing process is susceptible to interruption or failure which can lead to chronic wounds that do not heal.
Examples of factors that can impair wound healing may include disorders that impair microvascular blood flow such as cardiovascular disease and diabetes mellitus. Jaundice also impairs fibroblast function.
Types
Overview
Wound healing depends on the types of cells, tissue, chemical mediators, and structures involved. It can be divided into two main types:
- Primary intention – where the edges of skin in a wound are close together on opposite sides
- This is usually faster than secondary intention
- Bringing the skin edges together can facilitate primary intention (e.g. by stitching)
- This can only be done if the wound is precise with minimal disruption of surrounding tissues
- Examples of primary intention include using sutures, staples, or glues
- Secondary intention – where the edges of skin in a wound are not close together on opposite sides:
- This occurs when there is significant tissue damage or loss (e.g. major trauma) and the skin cannot be brought close together by stitching
- This is slower and requires the wound to heal from the bottom upwards
- The wound is left open and allowed to granulate and heal alone (new connective tissue and microvascular structures form):
- This requires regular wound care and has a higher risk of infection
Wound Healing Process
Haemostasis
Within minutes-hours following an injury, platelets aggregate and form a fibrin-rich clot to fill the wound.
Inflammation
During days 1-7, neutrophils migrate to the wound and phagocytose damaged/dead cells, debris and pathogens. Inflammation reduces and then the number of neutrophils at the wound site decrease in number. Inflammation is important for the removal of damaged/dead cells, debris, and pathogens, but excess inflammation can cause tissue damage. Therefore, if there is excess debris, necrosed tissue, or infection, excess inflammation can occur. On the other side, if a patient is immunocompromised, their inflammatory response may not be sufficient enough, resulting in prolonged inflammation. These can lead to the wound not being able to enter the proliferation phase, resulting in a chronic wound.
Proliferation
From days 4 to around 21 (or more), cytokines and growth factors result in the proliferation of fibroblasts (cells that produce extracellular matrix and collagen) which produce a collagen network. This leads to the formation of granulation tissue, resulting in a red/pink appearance of the new tissue. Factors promoting angiogenesis (e.g. vascular endothelial growth factor, VEGF) are released to promote the formation of new blood vessels, allowing further maturation of granulation tissue. Conditions reducing microvascular flow (such as cardiovascular disease and diabetes mellitus) can impair wound healing. Jaundice can also impair fibroblast function.
Remodelling
From 6 weeks to 1 year, collagen fibres are remodelled and deposited in the wound to provide strength and cells that are no longer necessary undergo apoptosis. Increased amounts of collagen deposition can lead to scar tissue formation. In wound healing by secondary intention, specialised smooth muscle cells called myofibroblasts contract the wound and bring the skin edges together.
Wound Categorisation
Overview
Wound contamination can lead to surgical site infection where pathogens gain entry to the body due to surgery. Wounds can be categorised into the following based on their infection rate, from lowest to highest:
- Clean (class 1):
- Uninfected, no inflammation is present, heals by primary intention
- Often seen in elective and non-emergency surgeries
- These wounds do not involve the respiratory, gastrointestinal, or urinary tracts
- Clean-contaminated (class 2):
- Often seen in urgent or emergency cases but lack features of contamination
- These wounds also include those affecting the respiratory, gastrointestinal, or urinary tracts, but under controlled conditions
- Contaminated (class 3):
- Fresh, open wounds due to accidents such as trauma, breaks in sterile techniques, or spillage from the gastrointestinal tract into the wound
- Incisions causing acute or lack of purulent inflammation are also class 3 wounds
- Dirty-infected (class 4):
- Old wounds with devitalised tissue present, often seen due to microorganisms escaping from perforating viscera, abscesses, or those present in the operative field before surgery
Scarring
Overview
The wound healing process requires a careful balance between each step and the duration and intensity of each one. Prolonged inflammation can lead to increased fibroblast proliferation and activity, resulting in excess collagen production and deposition. This leads to densely-packed collagen that is arranged differently than normal, resulting in excessively stiff tissue that can reduce surrounding tissue regeneration and impair communication between cells.
Scars tend to occur when the dermis (the innermost layer of the skin) is damaged and wound healing by secondary intention is at a higher risk of scar formation.
Hypertrophic scars
Excess collagen production results in the formation of a scar that is confined to the margins of the original wound. They are pink to red, may be slightly raised and flat, and usually occur within weeks of the injury. As mentioned above, a key feature of hypertrophic scars is that they remain within the confines of a wound, unlike keloid scars. They also tend to regress over time and improve with surgical interventions.
Keloid scars
More severe excess collagen production results in the formation of a scar that grows beyond the original wound margins (unlike hypertrophic scars) and may grow indefinitely. They do not regress over time and can recur following surgical intervention. Keloid scars may develop several months after the injury and are more common in people with darker skin tones.
See Keloid Scars for more.
Atrophic scars
Atrophic scars occur when structures under the skin (e.g. subcutaneous fat or muscle) are lost, resulting in sunken skin that looks pitted. Abnormal inflammation leads to reduced collagen synthesis and enzymatic hydrolysis of collagen fibres, resulting in atrophic scars. This type of scar is associated with acne, varicella zoster virus (chickenpox), and other skin infections.
Striae (stretch marks)
Striae (stretch marks) are a form of scarring that occurs when the skin is stretched over a quick period, such as rapid weight gain or loss, pregnancy, or growth spurts during adolescence. They are thought to be due to insufficient fibroblast activity and collagen synthesis to keep the skin supported as the skin is stretched, leading to skin tearing and resulting in more scar tissue formation. Both endogenous and exogenous corticosteroids (e.g. cortisol and prednisolone respectively) can impair fibroblast activity, accelerating this process, and also promote protein breakdown, which further contributes to the development of striae.
