Understanding the mechanisms involved in the healing of skin wounds provides insight into healing in general. The skin is composed of epidermis, which is made up of stratified squamous epithelium—the basal germinative layer of which is composed of labile (stem) cells—and dermis, which is composed of collagen, blood vessels, and skin appendages (adnexa) such as hair follicles, sweat glands, sebaceous glands, and apocrine glands. Stable cells make up the dermal connective tissue and adnexa.
Skin injuries are classified on the basis of the severity and nature of involvement.
The mildest form of skin injury is characterized by removal of the superficial part of the epidermis. Because the underlying basal germinative layer of labile cells is intact, the epithelium regenerates from below, and the integrity of the epithelium is restored with no scarring.
Incision (Cut) and Laceration (Tear)
Incisions and lacerations involve the full thickness of the skin (both epidermis and dermis) but with minimal loss of germinative cells. If the skin edges are carefully apposed, as in a sutured surgical incision, only a small gap remains to be repaired. Simple incisions constitute ideal skin wounds with regard to the healing process because they do not contain foreign material and are not infected. They therefore heal quickly and without incident. This process, in which necrosis and inflammation are minimal, is known as healing by first intention (see below).
Wounds with Epidermal Defects
Severe injuries (eg, crush injuries, extensive lacerations, burns) are characterized by denudation of large areas of the complete epidermis, including the basal germinative cells, with variable necrosis of underlying dermis. In contrast with an abrasion, the absence of labile epidermal cells at the base of the wound necessitates epidermal regeneration from surviving basal germinative cells around the margins. The extensive necrosis that is present in such wounds is accompanied by a phase of inflammation prior to the repair process (healing by second intention; see below).
Healing by First Intention (Primary Union)
Clean incised wounds and lacerations in which the edges of the wound are in close apposition heal by first intention (Figure 6-6; see also Figure 6-8). The small gap in the epidermis and dermis fills with clotted blood, which forms a scab and seals the skin opening within 24 hours to prevent the entry of infectious agents into the wound. The epidermis regenerates by rapid division of basal cells at the edges of the wound. These cells grow under the scab and reestablish continuity of the epidermis within 48 hours. As the epidermal cells mature and start shedding the superficial keratinized layers, the scab separates, usually at the end of the first week.
Healing of a surgical incision by first intention. A: Debris in the narrow gap between apposed skin edges is removed by neutrophils and macrophages. B: The epidermis regenerates rapidly, and granulation tissue in the dermal gap becomes collagenized to form a thin dermal scar (C).
Ten-day-old laceration of the face. The posterior part of the wound was sutured and has healed by first intention. The anterior part, which had a large skin defect, was debrided and permitted to heal by second intention. Note the much greater time needed for healing by second intention.
In the subjacent dermis, the wound fills with clotted blood and heals by scar formation. The small amount of clot and tissue debris is liquefied by neutrophilic enzymes and removed by macrophage phagocytosis. Neutrophils appear in the wound within 24 hours, rapidly complete the liquefaction process, and are usually replaced by macrophages by day 3. The growth of fibroblasts and new vessels (granulation tissue) into the prepared dermal gap begins within 48 hours, and collagen can be demonstrated there within 72 hours after injury. By day 5, the dermal gap is filled with a small amount of collagenizing granulation tissue (Figure 6-6). The amount of collagen increases for about 4–6 weeks.
The young scar that becomes visible when the scab separates from the skin is initially pink because of the vascularity of the dermal granulation tissue. Over the next few weeks the scar turns white as a result of a decrease in the number of blood vessels and an increased amount of collagen in the maturing scar. Eventually, the scar assumes normal skin color as the epidermis matures.
In the first postoperative week, a surgical incision is artificially held together by sutures, clips, or tape. When the sutures are removed at the end of the first week (leaving them in place longer increases the risk of wound infection), the tensile strength of the young scar is only about 10% that of normal skin. Scar strength increases to about 30–50% of normal skin by 4 weeks and to 80% after several months.
Healing by Second Intention (Secondary Union)
Wounds that fail to heal by first intention heal by second intention (secondary union [Figures 6-7 and 6-8]).
Healing by second intention of a large wound with extensive necrosis. A: The large area of tissue necrosis evokes acute inflammation with entry of neutrophils from the periphery. Slow liquefaction of debris and ingrowth of granulation tissue from the base (B) leads to scar formation (C). The epidermis regenerates slowly from the edges.
Reasons for Failure of the Primary Healing Process
Primary union fails to occur in the following circumstances: (1) in lacerations characterized by inability to achieve apposition of wound margins; (2) when foreign material is present; (3) when necrosis is extensive; and (4) when infection occurs. If infection develops after the skin edges are apposed, acute inflammation with suppuration leads to rupture of the wound and drainage of pus.
Process of Secondary Healing
The processes involved are essentially the same as those in healing by first intention but take much longer because of the more extensive damage. Infection is controlled by acute inflammation. The fluid exudate and necrotic tissue are then removed by enzymatic liquefaction, lymphatic drainage, and macrophage phagocytosis. Surgical removal of dead tissue and foreign material from the wound (debridement) greatly aids this clearing process. Granulation tissue then grows from the healthy tissue at the base of the wound and displaces the necrotic tissue toward the surface of the skin.
The epidermis regenerates from basal cells at the edges of the wound. In large wounds, reepithelialization may take several weeks. In these situations, surgical transplantation of skin (skin grafting) can help to speed healing.
When complete epithelialization of the surface of the wound has occurred, collagenization transforms the underlying granulation tissue to scar tissue. The eventual size of the mature scar is much smaller than that of the original wound as a result of contraction.
Skin appendages such as hair follicles and glands are regenerated if enough residual cells remain to provide a source of proliferating cells. In extensive skin wounds with total destruction of skin appendages, the resulting dermal scar is typically devoid of these structures.
Causes of Defective Wound Healing
(Table 6-3.) Surgeons must recognize the presence of any factors that impair healing because such adverse factors increase the overall risk of surgery and may even contraindicate surgery. If surgery is performed, recovery may take longer, and the risk of wound breakdown (which may be life-threatening) is also increased.
Factors That Adversely Affect Wound Healing.
Factors That Adversely Affect Wound Healing.
Poor blood supply (ischemia)
Presence of foreign material
Presence of necrotic tissue
Movement in injured area
Tension in injured area
- Vitamin C deficiency
- Zinc deficiency
Decreased number of neutrophils or macrophages
Cytotoxic (anticancer) drugs
Failure of Collagen Synthesis
Lack of collagen synthesis is one of the most common causes of defective wound healing and may result from vitamin C, protein, or zinc deficiency. Preoperative correction of negative protein balance with nutritional supplementation in malnourished patients improves the chances for uneventful healing.
Ehlers-Danlos syndrome is a group of rare inherited disorders characterized by defective collagen formation, hyperextensible joints, fragile tissues, and impaired wound healing. The basic defect appears to involve failure of cross-linkage of collagen chains (Chapter 2: Abnormalities of Interstitial Tissues).
Excessive Collagen Production
Synthesis of excessive amounts of collagen in wound healing results in formation of abnormal nodular masses of collagen (keloids) at the sites of skin injury (Figure 6-9A). Keloids often result from minor skin wounds and cause extensive disfigurement. Microscopic examination shows excessive collagen as thick, hyalinized bands (Figure 6-9B). Keloid formation tends to occur more frequently in blacks and demonstrates a familial tendency but with no recognizable single-gene inheritance pattern. The cause is not known. Excision of a keloid for cosmetic reasons is generally followed by formation of a new keloid.
Keloid formation. The keloid is an irregularly contracted skin nodule (A) composed of thick hyalinized bands of collagen (B).
Important local factors that cause defective wound healing include the following:
Foreign or Necrotic Tissue or Blood
The presence of foreign bodies, necrotic tissue, or excessive blood in the wound impairs healing. At surgery, foreign material and necrotic tissue should be removed and hemostasis ensured before the incision is closed.
Infection in the wound will result in acute inflammation and (commonly) abscess formation, with breakdown of the wound and delayed healing.
Ischemia due to arterial disease and impaired venous drainage both hinder wound healing.
Decreased Viability of Cells
Irradiation of a tissue or administration of antimitotic drugs in cancer chemotherapy is associated with poor wound healing. These facts have important implications for the management of cancer patients because the timing of surgery in relation to radiotherapy must be adjusted to minimize the risks associated with defective healing.
Diabetes mellitus is associated with impaired wound healing, probably as a result of deficient microcirculation and increased incidence of infection.
Excessive Levels of Adrenal Corticosteroids
Corticosteroid excess, whether due to administration of exogenous corticosteroids or to endogenous adrenal hyperactivity (Cushing's syndrome), is associated with impaired wound healing. Corticosteroids interfere with neutrophil and macrophage function.