Table 2.

Mechanisms found in failure to heal wound (FHW).

Wound	Cellular Mechanisms	Mediators
Inflammation Exudates Infection	Neutrophils’ excessive number and function Defective macrophages High number of mast cells Loss of microbiome diversity	Oxidative stress Wound proteases (MMPs, elastase, cathepsin G, and urokinase-type plasminogen activator (uPA)) Increase in inflammatory cytokines
Hyperkeratotic edge of the wound	Keratinocyte hyperproliferation and malfunction	Elevated b-catenin and c-myc
Failure to heal and close	Senescent fibroblasts	Degradation of VEGF, TGF-beta, and TNF-alfa

MMP: metalloproteinases; VEGF: vascular endothelial growth factor; TGF: transforming growth factor; TNF: tumoral necrosis factor.