Figure 1.

Wound-healing process. The wound healing process is commonly categorized into four distinct phases: (A) Homeostasis (coagulation); (B) inflammatory phase (early/ late inflammation); (C) proliferative phase (proliferation/migration/epithelialization/granulation); (D) remodeling phase (maturation/repair). (A) Hemostasis: A clot is formed, providing a temporary barrier to fluid loss and pathogen entry; acts as a reservoir of bioactive factors and antimicrobials; provides provisional extracellular matrix, which supports immune cell infiltration and migration; and initiates tissue repair pathways. (B) Inflammatory phase: Early step with damage-associated molecular patterns activation, free radicals, and reactive molecular species production to recruit immune cells; release of antimicrobial species; infiltrating immune cells that secrete amplifying alarmin signals (endogenous, constitutively expressed, chemotactic, and immune-activating proteins/peptides that are released as a result of degranulation, cell injury or death, or in response to immune induction), and activation of keratinocytes and fibroblasts. (C) Proliferation phase: Migration and proliferation of keratinocytes, fibroblasts, endothelial; resolution of inflammation; collagen/extracellular matrix synthesis; decreased vessel permeability; new capillary and lymphatic vessel angiogenesis; epithelialization; and de novo formation of granulation tissue. (D) Remodeling (maturation): Collagen/extracellular matrix turnover (synthesis and degradation); extracellular matrix reorganization and realignment; extracellular matrix contraction; endothelia and fibroblast apoptosis; repigmentation.