Skin Wound Healing Overview

Skin Wound Healing

• Two clinically significant types of repair are cutaneous wound healing and fibrosis in injured parenchymal organs
• Cutaneous wound healing is a process that involves both epithelial regeneration and the formation of connective tissue scars
• Healing can occur via primary (first) intention or secondary intention, depending on the wound's nature and size
• Primary intention healing involves a clean, uninfected surgical incision approximated by surgical sutures
• In primary intention healing, epithelial regeneration is the main repair mechanism
• A small scar is formed with minimal wound contraction in primary intention healing
• The narrow incisional space first fills with clotted blood, then granulation tissue, and finally new epithelium
• In primary intention, neutrophils are seen at the incision margin, migrating towards the fibrin clot, while basal cells show increased mitosis
• Epithelial cells from both edges migrate and proliferate along the dermis, meeting in the midline to form a thin, continuous epithelial layer
• By day three, neutrophils are replaced by macrophages, granulation tissue invades the incision space, collagen fibers are evident at margins, and epithelial proliferation continues. Results in a thickened epidermal covering layer
• By day five, peak neovascularization and abundance of granulation tissue occur from bridging collagen fibrils, normal epidermal thickness is recovered, and mature epidermal architecture with keratinization is seen
• During the second week, continued collagen accumulation and fibroblast proliferation take place with a diminished leukocyte infiltrate, edema, and vascularity
• Blanching is complete by end of second week by collagen deposition and vascular channel regression within the incisional scar.
• By the end of the first month, the scar consists of cellular connective tissue, largely devoid of inflammatory cells, covered by normal epidermis, and dermal appendages within the line of incision are permanently lost. Tensile strength of the wound increases with time.

Fibrosis in Parenchymal Organs

• Fibrosis is the excessive deposition of collagen and other extracellular matrix (ECM) components in tissues
• It is often used interchangeably with scarring
• Fibrosis mostly happens in internal organs during chronic diseases
• It's a pathological process caused by long-term injurious stimuli, such as chronic infections and immunological responses
• Fibrosis typically leads to tissue loss
• Could cause substantial dysfunction or organ failure
• Major cytokine in fibrosis is TGF-β
• Other important triggers seem to be cell death by necrosis or apoptosis and reactive oxygen species (ROS) generation
• Myofibroblasts are the primary source of collagen in organs like the lungs and kidneys, whereas stellate cells are the main producers in the liver.

Excessive Scarring

• Excessive scar formation causes hypertrophic scars and keloids
• Hypertrophic scars form due to collagen accumulation which leads to a raised scar. These scars tend to grow rapidly and contain lots of myofibroblasts
• These usually regress within several months. They frequently develop after injuries causing deep dermal damage
• Keloids are scars that grow past the original wound boundaries. They do not regress