Wound healing is divided into four overlapping states: 1) homeostasis, 2) inflammatory, 3) proliferative, and 4) remodeling.
Describe the overlapping phases of tissue repair
Wound healing is the process by which the skin, or any injured organ, repairs itself after injury. The main aim of wound healing is to prevent or limit further damage, to clean and seal the wound against infection, to restore tissue strength, and, if possible, tissue function.
Wounds in the skin can either be classed as epidermal (shallow, in which the dermis remains intact) or deep (in which the dermis is damaged; this is sometimes referred to as a full thickness wound).
The wound healing process can be characterized by four overlapping phases:
Upon wounding, the first phase of the wound response is concerned with maintaining homoeostasis within the body. Most wounds, even superficial shallow wounds, result in damage to the circulatory system. To prevent blood loss and reduce the chance of infection spreading throughout the body, circulation platelets within the blood begin to form a fibrin clot, which seals the wound site.
Additionally, vasoconstriction initially occurs around the wound site as a means of isolating the wound site. However, this is soon followed by vasodilation so the required cells are able to be recruited to the wound site. Factors are released from damaged cells, and those around the wound site initiate the inflammatory response. This phase is very quick.
Immune cells, such as neutrophils and macrophages, are attracted by factors released from the wound site and begin to accumulate, travelling through the circulatory system. These cells are responsible for the removal of debris and killing of bacteria that easily colonize the wound site, and prepare the wound for the proliferative/remodelling phase.
The proliferative phase can itself be divided into four phases; in the case of shallow wounds the first two steps may not occur:
Following closure of the wound, remodeling can occur. The epidermis proliferates and returns to its normal character; fibroblasts and immune cells which were recruited to the site are degraded; and the temporary extra cellular matrix that was laid down is remodelled into a stronger, more permanent structure.
The above mechanism describes a best-case scenario that results in the restoration of a fully functional dermis and epidermis. However, as the main aim of the wound healing process in the initial stage is to prevent further damage or infection, the intial stages can lead to a less than optimum result, as evidenced by the formation of scars. The larger and more severe the wound the more likely this is to occur.
The response to wounding is also susceptible to disruptions that can lead to the formation of chronic, non-resolving wounds such as ulcers; or the development of fibrosis if the proliferative phase does not resolve.
Epidermal wound healing describes the mechanism by which the skin repairs itself after injury.
Characterize epidermal wound healing
Epidermal wound healing refers to the repair of the epidermis in response to wounding. Epidermal only wounds are typically less severe than those affecting the dermis and so stages of the wound healing response may be missed.
As the epidermis is itself not vascularised—it is receiving blood from the dermis—a clotting and vasoconstrictive response is often not necessary. Immune cells may still be recruited to the wound site because the removal of the epidermal barrier makes the wound susceptible to infection.
Since the dermis is intact, local fibroblasts are able to contribute to the formation of a new basement membrane, upon which the epidermis sits. In very minor wounds even the basement membrane might remain intact, allowing for rapid re-epithelialization.
Keratinocytes—epidermal epithelial cells—around the wound site migrate across the wound and close it. Additionally, epidermal cells from dermal appendages, such as hair follicles, can contribute to wound closure.
Since the dermis and underlying tissue have not been damaged very little remodelling is required. As such, small wounds only in the epidermis typically heal rapidly and are often not observable (e.g., via the formation of scar tissue) within a period of months.
A deep wound involves the inner, deeper layers of the skin (dermis).
Describe the process of deep wound healing
Deep wounds that damage the dermis, or even the underlying muscle and fat, are more difficult to heal than shallow, epidermal-only wounds. The wound healing processes may be extended and scar tissue is likely to form due to improper re-epithelialization.
Additionally, deep wounds are more susceptible to infection, and also to the development of systemic infection through the circulatory system, as well as dysregulation that results in chronic wounds such as ulcers.
The wound healing process for deep wounds is similar to that of shallow wounds. However, with the removal of the dermis and its associated skin appendages, re-epithelialization can only occur from the wound edge, with no contribution from the dermal compartment.
Therefore, proper reconstitution of the epidermis is often only seen at the edge of the wound, with fibrous scar tissue—formed from the extracellular matrix (ECM) deposited during the proliferative phase—covering the rest of the wound site.
With the formation of a scar, the original physiological properties of the tissue are lost. For example scars are less flexible than skin, and do not feature sweat glands or hair follicles.
The ECM formed during wound healing may also be weaker in deep wounds, making the site susceptible to additional later wounding. The provisional ECM laid down during the proliferative phase is rich in fibronectin and collagen III that combine to allow quicker cell movement through the wound, which is very important during wound healing.
However, the ECM of mature skin is rich in collagen I. In large, deep wounds the remodelling of a fibronectin and collagen III-rich ECM to a collagen-I rich ECM may not occur, leading to a weakening of the tissue.
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