Wound Healing
last authored: Dec 2009, David LaPierre
Introduction
Wound Retraction - Although not considered part of the healing process, the first immediate change in the wound is usually enlargement through contraction of the surrounding musculature and an increase in resting tissue tension. This may give the illusion of tissue loss when there actually is not any.
Coagulation and Clot Formation - This begins to occur within minutes of the injury. The blood clot which forms will eventually dehydrate and contract, forming a scab and providing some degree of protection for the delicate healing tissue beneath. Platelet aggregation results in the release of mediators which increase capillary permeability and activate the inflammatory response. Fibrin plugs form in lymphatics and help prevent bacterial spread.
Hemostasis describes cessation of blood flow and formation of a clot.
Inflammation (reactive)
Inflammation begins within minutes to hours, and can be caused by physical injury, antigen-antibody reactions, or infection.
Increased capillary permeability and chemotaxis result in the presence of polymorphonuclear leukocytes and macrophages which rid the wound of bacteria and debris. In addition, they activate tissue fibroblasts and stimulate them to lay down collagen.
Thrombus releases factors such as PDGF, recruiting inflammatory cells.
Neutrophils almost immediately, closely followed by macrophages. Fibroblasts arrive within a few days.
- late inflammation 48-72 hours.
- >72hours: lymphocytes, peaking at day 7
Macrophages debride and remove dead tissue, recruit fibroblasts via secretion of IL-1, TNF-a, and TGF-beta. Wounds depleted of macrophages are slow to heal.
Proliferation (regenerative)
This phase begins within 2-3 days and lasts 2-4 weeks. Fibroblasts migrate inwards following chemoattractant signals from macrophages. They secrete collagen, elastin, and proteoglycans.
Overgrowth of scar tissue as inflammation resolves. Granulation tissue is composed of capillaries, fibroblasts, macrophages (to clean up debris), and collagen, fibronectin, and proteoglycans.
Neovascularization - Within days, angiogenesisi begins and new capillaries form and supply nutrients in addition to providing some initial bridging of the wound.
Collagen formation: begins day 5-7, increases in linear fashion; increase in ratio of I:III. Collagen provides tensile strength to tissues. fibroblasts will produce immature collagen - the precursor to scar tissue. Early collagen is a jelly like substance with little tensile strength. Fibroblasts will continue to produce new collagen for several weeks. In addition, they begin the process of collagen alignment and cross linking which is required for tensile strength in scar tissue
Epithelialization: detachment, migration, proliferation, differentiation, and stratification
Epithelial cells at the wound edge flatten, detach, and migrate across the open wound. Proliferation begins again once the wound surface is covered. Stratified squamous epithelium again begins to form as cells differentiate.
Within two days injury, a sutured wound will be completely covered with new epithelium. This process will take considerably longer in gaping wounds which are allowed to heal secondarily (not sutured - fill in on their own).
Maturation (remodeling)
3 weeks until 1 year post-injury
equilibrium between collagen synthesis and degradation
The capillary network supporting proliferation begins to regress, and collagen becomes organized along lines of skin tension.
Wound Contraction - Independent of collagen formation, wounds which are left open will begin to contract in size by 4 - 5 days. This process is less important in sutured wounds.
Scar Maturation - Collagen remodeling continues for up to a year following injury. This results in ongoing changes in size and bulk of scar tissue.
Factors Affecting Wound Healing
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Given time, most wounds will heal without suturing. The process will take longer and there may be a less cosmetic result, however there are some advantages which will be discussed later.
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Inflammation is a necessary part of wound healing and should not be confused with infection. A narrow margin of erythema (typically less than 1 - 2 cm) is usually indicative of a normal inflammatory response. Wider margins of erythema or erythematous streaking proximal to the injury often indicates infection.
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Although a wound may seem ‘stuck together’ soon after the injury, it has little tensile strength. The initial adhesion is caused by a combination of clot adhesion and neovascularisation. These wounds may reopen if placed under tension.
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Wounds do not begin to gain tensile strength from collagen until 5 - 7 days. Although collagen formation is complete within three weeks, a wound has only achieved ~ 20 % of its final strength by this time and ~ 60 % by four months.
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Scar tissue continues to remodel for at least 6 - 12 months after an injury. Patients may be distressed by the initial appearance of a scar, however decisions to revise an ‘ugly scar’ should be put off for at least a year.
Factors delaying wound healing
Delayed Wound Healing
The following factors may predispose to delayed wound healing:
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Infection
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Poor Blood Supply - locally in the wound or systemically i.e. peripheral vascular disease.
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Malnutrition - Vitamin C Deficiency (scurvy) is the classic example.
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Chronic Illness - Diabetes, Chronic Renal Failure.
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High Wound Tension - i.e. wounds over extensor surfaces of joints.
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Drugs - i.e. systemic corticosteroids.
Some of these factors may be modified i.e. proper wound cleaning to prevent infection, improved patient nutrition, closure techniques which reduce skin tension.
Risk of infection is increased with:
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Delayed presentation - wounds greater than 6 - 8 hours old are at increased risk.
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Contaminated wounds - organic material i.e. wood or feces are more likely to cause infection than are inert/inorganic materials such as glass or metal.
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Anatomic Site - areas with poor blood supply such as the distal extremities are higher risk than vascular areas such as the scalp or face.
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Devitalized Tissue - crushed or avascular tissue promotes bacterial proliferation
Bite Wounds - saliva has large numbers of pathogenic bacteria.
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Use of Local Anaesthesia with Epinephrine - causes local vasospasm and decreases blood flow.
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Presence of Subcutaneous Sutures - buried sutures provide a nidus for infection.
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Impaired Host Defenses - Immune suppressed or chronically ill patients are at highest risk.
Nutrition
- protein, zinc, iron
- vitamins A, C, E
Metabolic status
- diabetes - likely neuropathy moreso that ischemia
- obesity
Circulatory status
- atherosclerosis, cardiac failure
- wound tension
- smoking - nicotine is a vascoconstrictor and CO prevents oxygen release, both decreasing tissue perfusion
Drugs
- steroids - decrease inflammation and healing
- NSAIDs - decrease collagen synthesis
- chemotherapy
Age
- decreased rates of mitosis
- decreased tensile strength
radiation
- damages endothelium, fibroblasts, and lymphatics
Infection
- even subclinical infection can retard wound healing
- no healing with >105 bacteria/gram, or any beta-hemolytic strep
blood supply
- decreased perfusion impairs fibroblasts and ECM deposition, angiogenesis, and epithelializations
Mechanical movement
Foreign body
wound size (smaller, faster)
wound location
type of wound (clean
congenital diseases
- Pseudoxanthoma elasticum
- Ehlers-Danlos syndrome
- cutis laxa
- progeria (immature aging)
- Werner syndrome
- Epidermolysis bullosa
A partial-thickness wound heals via epithelialization, derived from the edges, hair follicles, and sweat glands.
There is minimal matrix deposition and wound contraction.
Granulation tissue is small, red granular foci which bleed easily and are commonly seen in freshly healing tissue. This is caused by fragile, newly formed capillaries which proliferate and invade damaged tissue along with fibroblasts.
Slough is the accumulation of dead cellular debris on the wound surface. It tends to be yellow due to the presence of leukocytes.
A scab, or crust, seal a wound but prevent new cells from crossing the wound, instead forcing them to burrow downwards. When the scab comes off, there will be a more noticable depression. For this reason, scabs should be avoided. Unless you like scars.
Wound contraction
important in healing wounds due to interaction between ECM and fibroblast, leading to fibroblast stimulation and differention into myofibroblast. Contractures are pathological shortening of scar tissue
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