ABSTRACT
Knowledge of the cell types and processes involved in wound healing is valuable for forensic pathologists who may be required to provide opinions regarding wound age in relation to the time of death. Wound healing occurs along a continuum with sequential overlapping phases.
There are four phases of wound healing:
Hemostasis – Starting almost immediately after injury, hemostasis establishes a fibrin-based provisional wound matrix and activated platelets release cytokines and growth factors in the wound to stimulate progression toward inflammation.
Inflammation – Within 30 minutes to a few hours, neutrophils and then macrophages recruited to the site of injury remove bacteria and cellular debris. Once cleared, macrophages polarize from a pro-inflammatory to an anti-inflammatory phenotype to trigger the proliferation phase.
Proliferation – Fibroblasts migrate to the site and proliferate to synthesize disorganized extracellular matrix (ECM). Endothelial cells also proliferate to form new blood vessels leading to granulation tissue formation. Keratinocytes migrate over the granulation tissue in skin and proliferate to close the wound.
Remodeling – Starting at approximately 2 weeks after injury, ECM remodeling occurs via the regulated activity of proteases. Scar tissue is removed and replaced by ECM with higher tensile strength approaching that of normal skin.
Cellular migration, proliferation and protein synthesis during the different phases of wound healing are regulated by cytokines, chemokines, growth factors and interactions with components of the ECM. Matrix metalloproteinases (MMPs) produced by epidermal cells, fibroblasts and vascular endothelial cells assist in migration of the cells, while proteolytic enzymes produced by macrophages remove ECM components during remodeling of the scar.
A number of local and systemic factors may affect the normal progression of wound healing including infection, foreign body, re-injury, diabetes, atherosclerosis, nutritional status and age.
