Wound Healing Fundamentals

Learning Objectives

• Students should be able to demonstrate an understanding of the phases of wound healing
• Students should be able to describe influences on the speed and completeness of wound healing

What is a Wound?

• A wound is a break in the continuity of any body tissue
• A wound does not always mean broken skin
• Wounds can be created through surgical procedures

Healing

• Images displayed show examples of wounds in various stages of healing

Stages of Wound Healing

• Wound healing is divided into three overlapping phases: Inflammation, Proliferation, and Maturation/Remodeling
• Some texts describe four stages, including haemostasis as a stage within inflammation
• Inflammation & Debridement:
  • Haemostasis
• Proliferation (or repair)
• Maturation and Remodel
• Microscopic events allow the wound to heal
• The macroscopic appearance of the wound gives insights into the stage of healing

Inflammation & Haemostasis

• Inflammatory phase starts with haemostasis
• First few minutes after injury
• Damage to blood vessels
• Blood and lymph escape, filling the wound
• Cleansing and preventing further contamination
• Reflex vasoconstriction (catecholamines, serotonin, bradykinin, histamine)
• Reduces blood loss
• Endothelial damage activates platelets, resulting in a platelet plug
• Vasodilation
• Increase in oxygen, white blood cells, and proteins to the area
• Endothelial damage exposes tissue factor
• Intrinsic coagulation cascade
• Fibrin plug forms
• Blood clot
• Barriers to infection
• Prevents further fluid loss
• Provisional Extracellular Matrix (ECM) framework
• Binding sites for neutrophils, macrophages and connective tissue cells
• Minimal wound strength but stabilises wound edges
• Dries to form scab
• Allows healing of deeper tissues

Inflammation & Debridement

• Migration of leukocytes into the wound within 6 hours
• Neutrophils (0-48 hours):
  • Destroy bacteria
  • Phagocytose
  • Release toxic oxygen species (NO)
  • Cause vasodilation
  • Component of pus
• Monocytes (48-72 hours):
  • Essential for wound healing
  • Transform into activated macrophages
  • Phagocytose/destroy bacteria
  • Remove clot
  • Debride necrotic tissue by phagocytosis and release enzymes (collagenase)
  • Produce pro-inflammatory mediators
  • Stimulates repair (growth factors)
• Fibroplasia (tissue repair)
• Angiogenesis (formation of new blood vessels)
• Epithelialisation

Gross Signs of Inflammation

• Heat, redness, swelling, pain, loss of function
• Open wound, blood clots, pus/serosanguineous discharge
• Vasodilation
• Increased permeability/extravasation of fluid
• Obstruction of lymphatic channels
• Stimulation of nerve endings due to pressure, stretching, or chemical stimulation (bradykinin)

Chronic Wounds

• Big inflammatory focus
• Not enough proteins/leukocytes for proper inflammatory response throughout the area
• Prolonged pro-inflammatory phase
• Persistent inflammatory focus
• Systemic inflammatory effects (SIRS)
• Continued vasodilation → hypotension
• CVS changes (tachycardia, vasoconstriction of non-essential organs = GIT)
• Barrier of GIT reduced
• Bacteria translocate into the Liver
• Hepatic inflammation → further systemic inflammation
• Renal failure, hepatic failure (MODS)
• Inappropriate Coagulation (DIC)
• Brain starved of nutrients
• Death

Summary of Inflammation and Debridement Stage

• Occurs immediately after the wound is created
• Generally lasts 2-5 days, though can be longer
• Immediate haemostasis (5-10 minutes) as platelets form a plug
• Acts as a barrier for further contamination
• Later, vasodilation occurs
• Neutrophils first, followed by monocytes which become tissue macrophages after 46-96 hours
• macrophages stimulate repair (fibroplasia, angiogenesis, epithelialisation)
• Debride necrotic tissue and phagocytose bacteria

Proliferation and Repair

• Restores skin integrity by filling the wound with new tissue
• Angiogenesis
• Fibroplasia
• Epithelialisation
• Granulation tissue
• Contraction

Proliferation: Fibroplasia

• Fibroblasts proliferate and migrate into the wound
• Differentiate into myofibroblasts
• Migrate along the extracellular matrix
• Synthesise collagen
• Initially collagen in the wound is Type III
• Type I collagen is stronger than Type III
• Once the wound is stable, fibroblasts stop producing collagen
• Capillaries regress and granulation tissue becomes a scar
• Requires oxygen and nutrition; perfusion must be good

Proliferation: Angiogenesis

• New capillaries form from existing vessels at the wound edges
• Endothelial cells migrate into the ECM
• Capillaries are fragile and highly permeable

Proliferation: Epithelialisation

• Migration of epidermal cells at the margin of the wound
• Proliferation of epidermal cells behind the leading edges
• Epidermis can only come from wound margins after granulation tissue has formed
• New epidermis may be visible 4-5 days after wounding
• In large wounds, healing may not complete in the middle
• Can be thin and easily traumatized in the middle of large wounds
• Adnexal structures do not regenerate
• Pigmentation is variable
• Healing occurs side to side, not top to bottom; long incisions heal as fast as short ones

Proliferation: Granulation Tissue

• Combination of new capillaries, fibroblasts, and connective tissue
• Fills wound beneath the scab/bandage
• Protects the wound
• No active dressing needed
• Barrier to infection
• No further antibiotics needed
• Surface for epithelialisation
• Contains myofibroblasts (help with contraction)
• Occurs (transition from ECM) ~4-5 days after injury
• Can take weeks to fill a large wound

Proliferation: Contraction

• Days 5-9 post injury
• Reduction in wound size
• Contraction of myofibroblasts
• Surrounding skin stretches (may look stellate)
• Can be a problem over joints/body openings
• Loss of function
• Continues until wound edges meet
• Negative feedback
• May cease if tension in surrounding tissue is too high

Summary of Proliferative Phase

• Occurs between days 4-21, dependent on contamination
• Fibroblasts enter the wound
• These can differentiate to myofibroblasts
• Collagen is formed
• Angiogenesis/neovascularisation occurs
• This results in the formation of new epithelium and fibrous tissue
• This will contract and lead to closure of the wound

Maturation/Remodelling

• Increases mechanical strength of the wound
• Reorganization of connective tissue
• Rearrangement of collagen bundles - crosslinking
• Reduction in collagen content
• Remodelling takes years
• Rate of remodelling differs between tissues
• Initial wound strength is weak (sutures, fibrin clot, epithelialisation)
• After 3-5 days, granulation tissue contributes (friable)
• After 7-10 days, collagen and scar tissue are present

Wound Strength Over Time

• Wound strength increases over time
• Inflammatory/debridement phase: low strength
• Repair/proliferative phase: moderate strength
• Maturation phase: high strength
• 80% normal strength after 1-2 years

Wound Healing Phases

• Vasoconstriction
• Vasodilation
• Inflammatory phase
• Cellular response
• Proliferative phase
• Re-epithelialisation
• Fibroplasia: collagen synthesis
• Wound contraction
• Maturation/remodelling phase
• Scar: collagen remodelling

Factors Affecting Wound Healing: Cats vs. Dogs

• 7 days post-skin incision
• Cat wound bursting strength is ~50% of dog's
• Granulation tissue appears slower in cats (6.3 days), compared to dogs (4.5 days)
• Time to cover wound completely with granulation tissue is longer in cats (19 days) than in dogs (7.5 days)
• Removal of subcutaneous tissue significantly reduces granulation tissue production in both species

Factors Affecting Wound Healing - Wound Factors

• Type of injury (forces applied); trauma vs. surgery
• Perfusion, blood supply, tissue viability, haematoma/seroma
• Contamination
• Anatomical location
• Movement, pressure, skin tension/availability
• Neoplasia
• Following tumor resections

Factors Affecting Wound Healing: Patient Factors

• Concurrent trauma
• Hypovolemic shock
• Poor nutritional status
• Other life-threatening injuries
• Consumption of platelets
• Pre-existing concurrent disease: Diabetes mellitus, hypothyroidism, HAC, infection, anaemia/coagulopathies, uraemia, hypoproteinaemia/poor nutrition, neoplasia
• Obesity
• Current medication: Immunosuppressive drugs/chemotherapy, radiation therapy
• Species: cat vs dog
• Wound interference

Factors Affecting Wound Healing: Surgeon Factors

• Technique: appropriate debridement, choice of lavage solution or an open wound management, Halsted's principles (meticulous haemostasis, obliteration of dead space, tension-free apposition of tissues), judicious and appropriate use of anti-microbials, avoiding prolonged anaesthesia and keeping surgical time as short as possible
• Decision-making in wound treatment
• Manage open vs. closed
• Type of closure

Fascia

• Slow healing due to fewer blood vessels
• No strength from healing tissue for 1-2 weeks (just sutures)
• Active zone up to 2 mm away from wound
• Sutures should be ~3 mm away from wound edge for security

Gastrointestinal Tract

• Anastomosis bursting strength decreases over first 48 hours
• Weakened tissue during inflammatory phase of healing allows for dehiscence (peristalsis)
• Lag phase; 3-5 days post-surgery
• Pre-existing septic peritonitis: less suture-holding capacity; already weakened at time of surgery
• Perfusion to anastomosis site is key
• CARE with drugs – NSAIDS – Can delay healing
• These patients often have hypoproteinaemia

Decision-Making with a Wound

• Can we attempt primary closure?
• Can we apply Halsted's principles?
• Would healing by granulation be a better option?
• Good communication with the owner is imperative.

What are Halsted's Principles?

• Gentle tissue handling
• Meticulous control of haemorrhage
• Strict asepsis
• Elimination of dead space
• Accurate tissue apposition
• Minimal tension

Underlying Disease for Healing?

• Does the patient have underlying disease conditions that could affect healing?
• Is it on any drugs that could affect healing?
• How long ago did this wound occur? (Golden period up to 6 hours)
• Was there blunt trauma?
• Was there a sharp penetration?

When Consider Delayed Closure?

• Long time since wounding (>6 hrs/golden period)
• Presence of gross contamination or infection
• Presence of necrotic tissue/devitalised/disrupted blood supply to skin edges/crushing injury
• Excessive tension on surrounding skin with attempted closure
• Excessive skin defect/degloving

Why is Blood Supply Important?

• Preserves blood supply, brings oxygen and leucocytes to the wound
• Leucocytes (neutrophils, monocytes, T-cells, B-cells, platelets) support tissue macrophages
• Tissue macrophages are essential for inflammatory response
• Provides acute phase proteins (complement and antibodies) that combat infection
• Fluid medium for inflammatory cells
• Maintains glucose delivery and metabolic waste removal
• Allows systemic response to inflammation (e.g., hyperthermia)

References

• BSAVA Manual of Canine and Feline Wound Management and Reconstruction
• Veterinary Clinics Small Animal Practice
• Stages of Wound Healing and Their Clinical Relevance
• Giselle Hosgood, BVSc, MS, PhD

Test your knowledge on wound healing with this quiz. Explore key concepts such as the definition of a wound, the phases of healing, and factors that influence recovery. Challenge yourself to identify true statements about wounds and the inflammation phase.