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Wound healing: physiological processes

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The physiological processes associated with wound healing can be divided into four phases: vascular response, inflammatory response, proliferation and maturation (Flanagan, 2000). Practitioners managing patients with granulating or epithelialising wounds need to be most familiar with the proliferative phase or stage.


The proliferative phase of wound healing is characterised by granulation, contraction and epithelialisation (Flanagan, 1998a). Granulation tissue, which was first identified by John Hunter in 1786 (Dealey, 1999), is composed of a newly formed wound matrix, consisting of collagen, matrix proteins and proteoglycans (Daly, 1990). This matrix provides the scaffolding into which new capillaries grow (Kindlen and Morison, 1997; Dowsett, 2002).

Capillary formation (angiogenesis) supports the augmentation of new connective tissue and the nourishment of macrophages and collagen-secreting fibroblasts (Daly, 1990; Flanagan, 2000). The presence of hyaluronic acid within the extracellular matrix stimulates the production of cytokines, for example transforming growth factor (TGF), which act on the macrophages to stimulate angiogenesis (Daly, 1990; Flanagan, 2000). Macrophages migrating to the wound are also stimulated into angiogenesis through contact with the hypoxic wound environment, caused by damage to the blood supply at the moment of injury (Silver, 1994).

The resultant granulation tissue in the wound is red in colour and often described as granular or grainy in appearance (Kindlen and Morison, 1997; Dealey, 1999; Dowsett, 2002).


Epithelialisation is characterised by the proliferation and migration of epithelial cells across the wound surface (Kindlen and Morison, 1997; Flanagan, 1998a; Dowsett, 2002). Re-epithelialisation occurs in two ways: first, in a ‘leap-frog’ fashion in which the epidermal cell migrates only two or three cell lengths from its initial position, sliding or rolling over the epidermal cells formerly implanted in the surface of the wound. Second, in an amoeboid fashion through the development of a membrane protrusion called a pseudopodium (see Figure) (Daly, 1990; Garrett, 1997; 1998).

Cellular movement stops when epithelial cells from opposite wound margins meet, which is known as ‘contact inhibition’ (Garrett, 1997; 1998). However, these are theories only - the true nature of epithelial movement remains uncertain (Garrett, 1997; 1998).

To enable the practitioner accurately to identify granulating or epithelialising tissue, the method of wound healing, that is primary or secondary intention, should be determined. In healing by primary intention, the wound edges are held together by artificial means, such as clips, sutures or staples. Wounds healing by secondary intention have a large area of tissue loss, making it impossible to bring the wound edges together; they are therefore left open and subsequently take longer to heal (Flanagan, 1998a).

In primary wound healing, granulation is not visible as it occurs deep within the closed wound (Flanagan, 1998b). In closed surgical wounds, epithelialisation occurs concurrently with collagen formation when epidermal cells migrate along suture tracks (Dowsett, 2002).

Wounds healing by secondary intention require a greater degree of granulation tissue, especially cavity wounds. Epithelialisation will not take place until the granulation tissue is on a level with surrounding healthy skin (Flanagan, 1998b; Dowsett, 2002). Fresh epithelial cells migrate from the wound margins, hair follicles, sebaceous glands or sweat glands across the granulation tissue until the wound is closed (Kindlen and Morison, 1997).

Wound assessment

When assessing granulating wounds, it is important for the practitioner to note the colour, texture and volume of granulation tissue present. Healthy granulation tissue should be pinky-red in colour, moist, shiny and should not bleed easily (Dealey, 1999; Flanagan, 1998b; Dowsett, 2002). Newly forming capillary loops are thin and fragile (Dealey, 1999), so are susceptible to trauma. Trauma and bleeding may occur when removing a dressing if an inappropriate type has been selected. Unhealthy granulation tissue may be dark red, bluish or very pale. It may appear dull, dehydrated and bleed easily (Flanagan, 1998b). Such tissue, when visible, may indicate ischaemia or infection in the wound (Harding and Cutting, 1994).

In some instances, it is possible for granulation tissue to continue forming within a wound or cavity even when granulation tissue has drawn level with the surrounding skin. This has been termed overgranulation, hypergranulation, exuberant granulation or hypertrophic granulation tissue (Dealey, 1999; Harris and Rolstad, 1994; Dunford, 1999). Hypergranulation tissue is usually visible as a pale or light purple uneven mass rising above the level of the skin (Harris and Rolstad, 1994). The presence of such tissue prevents epithelial migration across the wound, which delays wound healing (Dealey, 1999; Dunford, 1999).

Epithelialisation can take place once granulation is complete. Epithelialising tissue is usually visible at the wound margins. In larger, shallow, granulating wounds, such as leg ulcers, it can be seen as small islands on the wound surface (Dealey, 1999). Epithelialising tissue is translucent and pinky-white in colour (Dealey, 1999).

Assessment of patients with granulating or epithelialising wounds should not be confined solely to the wound’s appearance. Nutrition and psychological factors will also affect wound healing, and these should be considered in order to provide optimum wound management.

Nutrition - The role of nutrition is increasingly recognised as an essential component of wound healing. Some nutrients have a specific role during the proliferative phase. For example, protein is necessary for the development of granulation tissue; protein depletion can lead to poor collagen formation, reduced wound tensile strength and an increased risk of infection (Gray and Cooper, 2001; Williams, 2002). Vitamin A stimulates fibroblast production, and promotes epithelialisation and granulation (McIlwaine, 2003).

Vitamin C is central in the degree of cross-linking of collagen and angiogenesis - depletion can lead to reduced wound tensile strength and dehiscence (Casey, 2003). Minerals such as zinc, iron and copper have an important function in collagen formation and epithelialisation (Gray and Cooper, 2001; Williams, 2002).

Patients with wounds or those about to have surgery should be assessed, and members of the multidisciplinary team, such as the dietitian, should be consulted. This is particularly important for older people in whom wound healing is likely to be compromised due to age, when wound contraction and epithelialisation is slowed (Flanagan, 1998a).

Psychological issues - Factors such as wound pain should also be assessed. Addressing the issue can help to reduce the disruption of a patient’s sleep or rest patterns, and associated anxiety that can cause the release of glucocorticoids. These can inhibit collagen synthesis and granulation tissue formation (Flanagan, 1998a). Careful assessment and consideration of psychological issues can help the practitioner to plan appropriate interventions, for example pre-operative information-giving, in order to reduce factors that may prolong healing and thus achieve progression through the proliferative stage of healing and beyond.

Choosing a dressing

The choice of modern wound dressings (see Table) can make selection difficult. The use of an inappropriate dressing may result in pain and trauma on its removal, along with damage to the friable and delicate tissue underneath.

Granulating wounds - Dressings for granulating tissue should provide a moist environment, fluid-handling properties and good thermal insulation. Granulation tissue formation is also enhanced by acidic conditions (Thomas, 1990). Management will depend on wound depth and how much granulation tissue is required to fill the wound before epithelialisation can take place, and the amount of wound exudate (Dealey, 1999).

Shallow granulating wounds with low to moderate exudate can be managed with film dressings, foams, hydrocolloids or hydrogels (Dealey, 1999).

Film dressings, which are transparent, make continual assessment of the wound possible without the need to remove the dressing. They are also vapour permeable while preserving the ability to retain moisture. However, maceration can occur if excessive exudate is allowed to accumulate under the dressing (Jones and Milton, 2000a).

Foams provide a soft absorbent dressing for granulating wounds (Jones and Milton, 2000b). They are especially useful for dressing awkward areas such as the sacrum or heels (Jones and Milton, 2000b; Fletcher, 2003), as they come in a range of shapes and sizes. Non-adhesive foams can be cut to size while adhesive foams remove the need for additional retention dressings. They can be left in situ for up to seven days, dependent on the level of exudate (Pudner, 1998). Foams are often the dressings of choice in managing hypergranulation tissue (Harris and Rolstad, 1994).

Hydrocolloids have been found to be of benefit, although this conclusion was based on clinical observation of effect (Young, 1997). The use of caustic substances such as silver nitrate has also been cited (Dunford, 1999). However, prolonged use can cause hypokalaemia, hyponatraemia and hypocalcaemia (Dealey, 1999), and their long-term use should be discouraged.

Anecdotal evidence suggest that topical steroids have been used to diminish the inflammatory response, but they may prolong healing (Dunford, 1999; Young, 1995). They should be used as a short-term measure only (Dunford, 1999). According to Young (1995) applying light pressure to the wound bed may be an appropriate treatment, but in many cases hypergranulation may resolve without intervention.

There is no conclusive evidence to support the use of any of these treatments and further research on the management strategies for hypergranulation is required.

Hydrogels are suitable for granulating or epithelialising wounds as their high water content support a moist wound environment (Jones and Milton, 2000c; Trudigan, 2000; Vernon, 2000). However, they require a secondary dressing and are not suitable for heavily exuding wounds (Pudner, 2001), particularly over a weight-bearing surface such as a heel.

Cavity wounds - In cavity wounds containing granulation tissue, dressing choice should be governed by the shape of the cavity and the presence of any tracking downward under the base of the wound or sinuses (Dealey, 1999). Foam-cavity dressings, pre-formed or custom made, can be used but care must be taken to ensure that the wound entrance is larger than the cavity itself to facilitate easy removal (Fletcher, 2003). Wounds can also be lightly packed with alginate ribbon, rope or hydrofibres (Dealey, 1999; Dowsett, 2002).

Newer treatment modalities, for example vacuum-assisted closure (VAC) therapy have also been used successfully to promote granulation by reducing oedema and stimulating angiogenesis in cavity wounds and chronic wounds such as leg ulcers, pressure ulcers and dehisced incisions (Collier, 2003).

Epithelialising wounds require a dressing that should be permeable, maintain an acidic pH and a moist environment, but that should not adhere to the wound surface, causing trauma on removal (Thomas, 1990). Suitable dressings include foams, films, hydrocolloids and hydrogels (Dealey, 1999).

Wounds healing by primary intention are usually left covered for 48 hours or until exudate or superficial bleeding has stopped (Gould, 2001; Dowsett, 2002). Island, tulle or non-adherent dressings, semipermeable films or hydrocolloids may be used (Briggs, 1997).

Other factors to consider in the management of granulating or epithelialising wounds include the methods of wound debridement and cleansing. Such interventions should avoid unnecessary trauma to the newly forming granulation tissue or capillary loops. Wound cleansing solutions should be warmed to prevent disturbance of the mitotic activity of cells at the wound surface. Solutions containing antiseptics should also be avoided, as these may prove toxic to the granulating tissue (Flanagan, 1998b).

An understanding of the underlying physiology of wound healing is essential to the successful management of patients with granulating or epithelialising wounds. It enables the practitioner to identify healthy and unhealthy tissue.

There is a wide range of dressings suitable for use on granulating or epithelialising wounds. Practitioners must use their knowledge and follow the manufacturer’s instructions, or consult with expert practitioners to make appropriate, evidence-based product selections.

Author’s contact details

Karen Lay-Flurrie, Staff Nurse, c/o Windsor Day Hospital, Hemel Hempstead General Hospital, Hillfield Road, Hemel Hempstead HP3 4AD; email: Karen

Useful resource

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Latest Policy

Granulating/epithelialising wounds: management options

- There are no specific national guidelines on managing granulating or epithelialising wounds. However, the RCN et al (1998) has clinical practice guidelines regarding specific wound types, such as managing patients with venous leg ulcers. Other guidelines, such as the National Institute for Clinical Excellence’s guidelines on pressure ulcer management, are under development

- Nurses should familiarise themselves with their trust’s wound-care guidelines or regional guidelines. This is especially important in areas such as the management of hypergranulation, where no consensus of opinion exists on the most effective management strategies



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