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Chapter 2.5.1
Module:  2.
Nutritional supplements bioactivity, functional properties and safety: in vitro & in vivo studies
Unit:  2.5.
Animal and cell culture models of skin homeostasis and repair, and cancer
Chapter:  2.5.1.
Models of acute and chronic wound healing

A wound is defined as a disruption in the epithelial lining of a living tissue due to physical, chemical, thermal damage, microbial or immunological insults. This break in the epithelial integrity can be divided into two categories, acute and chronic wound, based on the duration and nature of the healing process. Specifically, an acute wound is the result of an accident or surgical injury, while the time of its healing process is usually 8-12 weeks, dependent on the size, depth, and the extent of damage. On the other hand, conditions such as decubitis ulcer and leg ulcer, create chronic wounds that are not able to heal through the normal stages of healing in a predictable timeframe as acute wounds.

Wound Healing Stages

The dynamic and complex process of wound healing consists of four different phases; the coagulation and hemostasis phase (immediately after injury), the inflammatory phase, (shortly after injury, when swelling takes place), the proliferation period, where new tissues and blood vessels are formed, and the maturation phase, in which remodeling of new tissues. After a tissue injury, blood vessels are disrupted and exposed platelets play a crucial role in the first step of wound healing, known as hemostasis. Hemostasis consists of two major processes, the development of a fibrin clot and coagulation. Platelets release chemoattractants and growth factors that trigger the initiation of the second phase of the healing process. Recruited leukocytes, first neutrophils and later macrophages, lymphocytes, and mast cells, infiltrate the wound and clean the area by removing damaged tissue debris and foreign particles. Upon activation, macrophages also release several important growth factors and cytokines. Thereafter, resident dermal fibroblasts nearby proliferate and migrate into the wound clot to produce collagen-rich matrix, resulting in the formation of contractile granulation tissue that assist the wound margins to close together. Meanwhile, the epidermal cells (keratinocytes) on the wound edges migrate to fill the wound space, reconstituting the epidermis (re-epithelization).

Factors Affecting Wound Healing Process

Consequently, wound healing is a multi-step process that relies on interactions among cytokines, growth factors, blood and the extracellular matrix (ECM). The ECM forms a three-dimensional structure and is composed of extracellular macromolecules, such as collagen, elastin, fibronectin, vitronectin, integrins and laminins, providing structural and biochemical support to surrounding cells. In the wound, ECM molecules act either as substrate scaffolds to facilitate processes such as differentiation, migration and proliferation, or interact with cells through transmembrane cell surface receptors, mediating signal transduction. During the hemostasis phase, platelets release platelet-derived growth factor (PDGF), transforming growth factors (TGF)-a and -b, fibroblast growth factor (FGF)-2, epidermal and endothelial growth factors as well as chemotactic factors. Additionally, fibroblasts produce vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), while lymphocytes modulate healing through the release of several growth factors including interleukin-1 (IL-1), tumor necrosis factor (TNF), fibroblast-activating factor, and macrophage-activating and inhibitory factors. Therefore, ECM molecules combined with cytokines and growth factors regulate distinct processes in the overlapping phases of wound healing.