Wound Healing Overview

Wound Healing

• Healing, in a pathological context, is the body's replacement of damaged tissue with living tissue.
• A wound is a breach or defect in intact living tissue, caused by injury and accompanied by inflammation.
• Wounds can be accidental or surgical.

Types of Wounds

• Closed Wounds: Skin surface is intact, but underlying tissues are damaged (e.g., contusions, hematomas, Stage 1 Pressure Ulcers).
• Open Wounds: Skin is split or cracked, exposing underlying tissues to the environment.

Processes of Wound Healing

• Regeneration: Replacement of lost tissue with similar tissue types.
• Repair (healing by scarring): Replacement of lost tissue with granulation tissue that matures into a scar.
• Healing type depends on the damaged organ's cell type and stromal framework integrity.

Types of Cells

• Labile Cells: High proliferative capacity, found in surface epithelium of GI tract, urinary tract, and skin; lymphoid and hematopoietic cells; excellent regeneration potential.
• Stable Cells: Lower replication rates, few stem cells; can undergo rapid division in response to injury; smooth muscle cells, fibroblasts, osteoblasts, endothelial cells; good regeneration potential. Liver, endocrine glands, and renal tubular epithelium can regenerate.
• Permanent Cells: Non-dividing; cannot be replaced if lost; adult neurons, striated muscle cells, lens cells.

Objectives of Wound Healing

• Restore an intact epithelial surface.
• Restore tensile strength of sub-epithelial tissue.
• Wound healing is a complex, orderly, systematic process that involves seven processes:
• Acute inflammatory response upon injury
• Regeneration of native cells of tissue involved.
• Proliferation and migration of native and connective tissue cells.
• Synthesis of extracellular matrix (ECM) proteins.
• Remodelling of connective tissue and parenchymal components.
• Collagenization and progressive acquisition of wound strength.
• Contraction.

Growth Factors

• Healing is, in part, mediated by growth factors—low molecular weight polypeptides stimulating cell division and proliferation.
• Sources of growth factors include platelets, circulating serum growth factors, macrophages, and lymphocytes recruited to the injury site.

Healing by Regeneration

• Regeneration is the renewal of lost tissue by replacing lost cells with identical ones.
• It involves two processes: proliferation of surviving cells to replace lost tissue and migration of surviving cells into the vacant space.
• Regenerative capacity depends on tissue's proliferative ability, degree of damage, and damage severity.

Wound Contraction

• Mechanical reduction in wound size, typically 70-80% of original size.
• Faster healing due to reduced tissue needing replacement.
• Slow and large ugly scar formation if prevented.
• Myofibroblasts—features intermediate between fibroblasts and smooth muscle cells—cause contraction.
• Migrate to wound site 2-3 days post-injury, decreasing wound area.

Patterns of Wound Healing

• Healing by First Intention (Primary Union): Clean, uninfected surgical wounds with well-approximated sutures heal quickly. Minimal epithelial and connective tissue cell death; minimal basement membrane disruption. Immediately filled by clotted blood which dehydrates to form scab.
• Healing by Second Intention: Extensive cell loss, large tissue defects; wide margins; includes infarction, inflammatory ulceration, and abscesses. Requires abundant granulation tissue, more fibrin, necrotic debris, and a significant inflammatory reaction for healing. Myofibroblasts are important for wound contraction, which is critical for healing large wounds.

Granulation Tissue

• New connective tissue with microscopic blood vessels and myofibroblasts forming at wound site during healing.
• Fills wound spaces; crucial for wound contraction and epithelial cell migration.

Factors Influencing Wound Healing

• Local Factors: Type, size, location of wound, vascular supply, infection, movement, ionizing radiation.
• Systemic Factors: Circulatory status, infection, metabolic status, nutritional deficiencies, anti-inflammatory drugs.

Complications of Wound Healing

• Infection: A wound provides a portal of entry for microorganisms and delays or stops healing. Severe infection may cause extensive granulation tissue formation (proud flesh) and possible large, deforming scars.
• Deficient Scar Formation: Inadequate granulation tissue formation or inability to form suitable extracellular matrix; leads to;
• Wound dehiscence and incisional hernias: Improper sutures, infection; increased mechanical stress by vomiting, coughing, or ileus are risk factors.
• Ulceration: Inadequate blood supply, insufficient vascularization, and persistent trauma may lead to ulceration. Commonly found in diabetics, leprosy, and tertiary syphilis.
• Excessive Scar Formation: Excessive extracellular matrix deposition; leads to:
• Hypertrophic scars: Raised or thickened scar tissue.
• Keloids: Prominent, raised scar tissue extending beyond the wound boundaries.
• Contractures: Excessive wound contraction; can restrict movement or function.

Fracture Healing

• Unlike skin wounds, fracture healing involves specialized bone-forming tissue.
• Bone is comprised of calcified osteoid tissue (collagen and osteomucin matrix)
• Woven (immature/non-lamellar) bone shows collagen bundle irregularity.
• Lamellar (adult) bone has parallel collagen bundles in sheets.
• Fracture healing process occurs in seven stages, including hematoma formation, inflammation, demolition, granulation tissue formation, woven bone/cartilage formation, lamellar bone formation, and remodeling.