Wound healing

Stages

1. Inflammation
   1. Haemostasis (damage limitation) - erythrocyte and platelet plug
   2. Inflammation - increased permeability, migration, and activation
      1. Initial neutrophils
      2. But healing is largely mediated by macrophages - arrive as monocytes within 24-48 hours of injury, release a lot of chemokines/cytokines
      3. Lymphocytes appear day 5-7 - seem to be related to downregulating healing as wound closes. Can be affected by drugs that suppress T-lymphocyte function (steroids, cyclosporine, tacrolimus)
      4. Can continue up to two weeks
2. Proliferation
   1. Acute response is over - scaffolding laid for repair of wound - formation of granulation tissue (capillary bed, fibroblasts, macrophages, and collagen etc scaffolding)
   2. Growth factors secreted, primarily by macrophages, which recruit the fibroblasts
3. Maturation/remodelling/epithelialisation
   1. Centripetal movement of the whole thickness of surrounding skin
   2. Complex interaction of ECM and fibroblasts (which have changed to become myofibroblasts)
   3. Remodelling occurs as type III collagen is largely replaced by mature type I collagen

Wound classification

Type 1 - clean	Uninfected operative wound with no inflammation and no entering of special tracts Heal with negligible risk of infection Primary closure is best
Type 2 - clean contaminated	Operative wounds where the respiratory, alimentary, genital, or urinary tracts were entered under controlled conditions Only minor spillage Close primarily after wound toilet
3 - contaminated	Open, fresh, accidental wounds Operative where non-purulent inflammation is present Operative with major break in sterile technique or spillage from GIT Need copious irrigation before delayed primary or sometimes primary closure
4 - dirty	Infected, contaminated, or devitalised wounds (the organisms causing post-op infection were present prior to the operation) Includes perforated viscera Open wounds >12 hours Need to be converted to type 1 or 2 prior to closure

Primary intention

• Fibrinous adhesions between surfaces by 24 hours
• Granulation tissue grows in
• Collagen is laid down
• Wound contracts, scar forms
• 10% strength at day 5, 50% at day 21

Secondary intention

• Clot on surface allows moist environment at base of wound
• Debrided by phagocytic WBCs
• Collagen produced by fibroblasts in a matrix of mucopolysaccharides - granulation tissue
• Myofibroblasts cause wound contraction
• Epithelium migrates to cover wound

Management of clean surgical wounds

• Fibrin layer forms within the first few days, especially if subcuticular suture is used (takes a bit longer with staples)
• Dry gauze on top is only necessary for about three days; after that, can be uncovered, or dry gauze at most (opsite)
• Can bathe/shower (in clean water) after five days
• A red area of a surgical wound does not mean cellulitis - it means pus that needs to be drained. Drain it locally by removing a few sutures or staples and then continue to observe it. If the cavity probes elsewhere, may need to open further.
• Only give antibiotics if there is severe cellulitis or fascia is involved
• Wound swabs are generally unnecessary, unless the wound is becoming problematic and MRSA may be involved

Chronic/non-healing wounds

• Occurs when the normal healing process is disrupted, most often because an underlying disorder causes a prolonged, unchecked pro-inflammatory state
• There often seems to be inhibition of growth factors and other negative implications on a cellular level

Factors influencing wound healing

(>90% of ulcers are associated with either chronic venous insufficiency, arterial occlusive disease, or diabetic neuropathy)

Local

• • Ischaemia
    • Inadequate inflow - vessel ligation, PVD, systemic hypotension
      • See separate topics
      • Use WIfI classification to determine severity and guide intervention
      • Toe pressure can be useful in guiding chance of wound healing
      • In general same principles apply as for other wounds - pressure offloading, debridement of non-viable tissue, infection control, moist wound healing
      • Leave adherent eschar or dry gangrene in place until revascularisation has occurred
      • After revascularisation, be aware of limb oedema
        • For grafts ending at popliteal level, below-knee IPC is useful
        • For grafts ending distally, a pedal compression boot is useful
      • Common for infection to develop as areas of eschar/dry gangrene heal - need to be followed closely. Some surgeons prefer to amputate necrotic digits or perform wide debridements of eschar a few days after revascularisation.
    • Dead tissue at wound edge
    • Overly tight or closely spaced sutures
    • Tension on wound edge
    • Smoking - 30% reduction in wound blood flow
  • Tension
  • Dead space
  • Foreign bodies/contamination
  • Infection
    • Collagenolysis increases, tissue pressure elevates
    • Mechanical and antibiotic therapy can decrease bacterial count, reduce inflammation, and allow wound closure
    • See separate topic: 'wound infection'
  • Haematoma
    • Predisposes to infection and wound complications
  • Local trauma
  • Chronic tissue factors
    • Chronic venous insufficiency
      • Venous disease in any combination of anatomic sites may result in limb ulceration, including superficial venous insufficiency alone, however most of the time a venous ulcer is present, there is involvement of the deep venous system (see below)
      • Chronic upregulation of pro-inflammatory cytokines appears to mediate the development of tissue fibrosis and the clinical appearance of lipodermatosclerosis (which is believed to be a pre-ulcerative condition). Ulceration eventually occurs secondary to minor trauma.
      • Should have an USS to assess for this (saphenous reflux, perforator incompetence, and iliac outflow stenosis, etc)
      • Sustained high-strength compression of the limb is the basis for treatment of venous leg ulcers, and must be maintained throughout treatment. Results in healing in 60-70% of patients after 4-6 months.
      • Venous intervention is recommended whenever superficial venous reflux is a prominent component of the abnormal venous function. Limited evidence supporting the removal of varicose channels extending into the ulcer bed.
      • Other therapies have been studied including skin grafting, but this is only useful in select cases
    • Lymphoedema, ischaemia, scarring
  • Sutures
    • Silk - nidus for infection
    • Too tight?
  • Irradiation

General health

• • Diabetes
    • Macrovascular disease and microangiopathy
    • Sensory neuropathy - repeated trauma
    • Immunosuppression
  • Advanced age
  • Malnutrition
    • Vitamin C
    • Vitamin A
  • Mineral deficiencies
    • Zinc
    • Iron
  • Immunosuppression
  • Medications
    • Corticosteroids
    • Chemotherapy
  • Smoking
  • Systemic illness

Approach to a chronic/non-healing wound:

• Review all potential contributing factors from above
• Check for granulation tissue - most negative factors above will stagnate the wound in the inflammatory phase
• Remember that many rare causes of non-healing wounds can only be diagnosed with biopsy!
• Wagner classification system:
• Wound bed preparation:
  • Debridement of non-viable tissue
    • Remove callus, eschar, fibrinous material, and slough. None of these have regenerative capacity, and they harbour bacteria, and prevent migration of healthy epithelium.
    • Chemical debridement is possible, mostly using collagenase, and this is most effective at removing a moderate amount of fibrinous slough from the wound base, but is ineffective against thick tissue or eschar
    • There are many methods of debridement, but none have ever been found to be superior to standard surgical debridement
  • Identification and correction of bacterial involvement
    • Controversial as to whether wounds that are colonised but not clinically infected should be treated
    • Rutherford's says wounds with poor progress or any evidence of enlargement or infection should have quantitative cultures, and anything growing to >10^5 bacterial counts per cubic mm should be treated with systemic therapy, guided by sensitivities
    • It is advantageous to remove biofilms where possible
  • Control of chronic inflammation
  • Elimination of limb oedema
  • Control of wound exudate

Hypertrophic scars/keloids

• Excessive net collagen deposition
• Keloids grow beyond borders of original wounds
  • Rarely regress
  • Aetiology
    • Much more prevalent in dark skin
    • Genetics
  • Pathogenesis
    • Disorganised type I and III collagen
  • Clinical features
    • Often form at previous minor trauma/scars e.g. earlobes from piercings
    • Generally get bigger over time, do not regress
    • Often a/w pain and pruritis
  • Treatment
    • Medical
      • Topical/intralesional corticosteroids
      • Radiotherapy (often in conjunction with surgery, however one big study didn't show any difference to recurrence rates if it was included)
    • Surgical
      • Consider if refractory to medical treatment for 12 months
      • Leads to recurrence of 45-100%
• Hypertrophic scars are raised scars within confines of original wound
  • Occur with prolonged inflammation and tension
  • Frequently regress spontaneously
  • Well-organised type III collagen
  • Prevent by avoiding wound tension, hydration/occlusion, and use of taping/pressure garments
    • Indicated in severe burns, mechanical trauma, necrotising infections, or grafting
  • Treatment:
    • 6-12 weeks: pressure therapy
    • >6mo: silicone therapy, intralesional corticosteroids (triamcinolone acetonide, 10-40mh/mL injected into papillary dermis every 2-4 weeks until flat. Works >50% of patients
• Approach to hypertrophic scars/keloids:
  • History - including other scars, family history
  • Examination - can use Vancouver scar scale to give objective measure of scar
  • Counsel patient about difficult nature of problem and define goals of therapy:
    • Relief of symptoms
    • Reduction of scar volume
    • Functional or cosmetic improvement
  • Initial trial of intra-lesional triamcinolone acetonide at a concentration of 10 to 40mg/mL
    • Reduces volume
    • Improves pain and pruritis
    • Repeat treatment several times at 4-6 week intervals
    • Injections are painful. Can cause dermal atrophy, skin ulceration, hyperpigmentation, telangiectasia.
  • Can try combination fluouracil and triamcinolone - 50-96% had a good response in one meta-analysis - but these studies are of low quality. Can cause pain and hyperpigmentation.
  • Can trial pressure - there are special devices for earlobes. Limited evidence. May be beneficial in combination with surgery.
  • Surgery - recurrence approaches 100% - however is probably lower if combined with peri-operative triamcinolone or fluorouracil
  • Post-op radiation therapy. Evidence from retrospective observational trials.