Question:
A 78-year-old male undergoes Mohs procedure for a basal cell carcinoma on the scalp and the wound is left to heal by secondary intention. Which of the following cells is considered the most important and necessary cell type for wound healing to occur?
A. Platelet
B. Neutrophil
C. Macrophage
D. Fibroblast
E. Myofibroblast
Rationale:
There are four main phases of wound healing: 1) coagulation 2) inflammatory 3) proliferative and 4) remodeling. Platelets, neutrophils, macrophages, fibroblasts/myofibroblasts, endothelial cells, and epithelial cells all play an important role in different phases of healing.
Correct answer: C. Macrophage
Macrophages are required for wound healing to occur. Macrophages are present in the wound at around 72 hours. As phagocytic cells, they also release proteolytic enzymes and create a hypoxic environment stimulating certain growth factors that are critical for the proliferative phase of wound healing to occur.
Incorrect answers:
A. The coagulation phase is the first stage of wound healing and occurs within hours of tissue damage. Platelets are the first cells to arrive at the site of vascular injury and the extrinsic and intrinsic coagulation pathways are activated leading to the formation of a fibrin clot.
B. The inflammatory phase initially involves the influx of neutrophils which help clear bacteria or debris. Macrophages arrive after neutrophils and help phagocytose tissue and organisms and secrete proteolytic enzymes and growth factors which are critical for the growth of fibroblasts and endothelial cells.
D and E. The proliferative phase occurs when fibrogenic growth factors (released by macrophages) stimulate fibroblasts to produce the components of the extracellular matrix and the development of granulation tissue. Re-epithelialization occurs during this phase as keratinocytes are stimulated by various growth factors as well as neovascularization due to various factors that increase angiogenesis such as the release of VEGF. Myofibroblasts help to contract the wound. The remodeling phase ensues and is frequently the longest phase. Remodeling involves the release of matrix metalloproteinases, the breakdown of granulation tissue, and the creation and destruction of collagen. Complete remodeling can take up to 1 year.
Additional reading at Fitzpatrick's Dermatology Chapter 149: Wound Healing