# Recent Studies on the Healing Properties of Eicosapentaenoic Acid
## 2 Skin and Its Healing Mechanisms  
The skin, which covers 1.85 m\({}^{2}\) of surface area on average, is the biggest organ in the human body. It is the natural barrier against pathogenic microbes, extreme temperature, mechanical damage, toxic agents, and UV radiation [6]. According to their impact and underlying causes, skin wounds are divided into acute and chronic categories [7]. In contrast to chronic wounds, which are challenging to heal, acute wounds typically heal in 4-12 weeks with the recovery of the functional and anatomical integrity of the skin. Chronic wounds take longer to heal, a fact that increases the risk of infection and hinders the full and effective restoration of skin integrity. Adults usually exhibit scarring rather than total tissue regeneration as a result of persistent or deep wounds. The epidermis, dermis, and subcutaneous adipose tissue, which run from the outer to the inner skin layer, must cooperate to perform particular sequences to foster healing when the skin is wounded. There are four stages of healing, which include hemostasis (I);inflammation (II); proliferation (III); and granulation tissue creation, re-epithelialization, and (IV) remodeling, which take place in a certain order or overlap. Trauma causes the wounded blood vessels to restrict first, followed by the activation of platelets to form a clot. The clot seals the wound temporarily, preventing the spread of germs, and serves as a scaffold for arriving inflammatory cells [8]. Damaged epithelial and endothelial cells, along with the clot, generate several chemotactic substances that draw in inflammatory cells to commence the following phase of healing. After hemostasis, the inflammatory phase follows, where immune cells travel to the site of the wound as a reaction to damage signaling factors to ward off microbial infection [7]. At the location of the wound, there is an inflow of various inflammatory cells, that consequently produce a range of mediators and cytokines that facilitate angiogenesis and re-epithelialization. Hemostasis, chemotaxis, and enhanced vascular permeability are the characteristics of the inflammatory phase, which limit additional damage, seal the wound, cleanse cellular debris and microorganisms, and accelerate cell migration [9]. The clot thrombus is instantly inhabited by neutrophils as the first line of resistance against pathogens. Within 48-96 h of injury, monocytes are drawn in to change into tissue-activated macrophages in the damaged area. To fight self- and foreign antigens, the adaptive immune system, which consists of Langerhans cells, dermal dendritic cells, and T cells, is also activated [8]. Acute phase signals are first presented to skin cells, which are then recognized by toll-like receptors that start and maintain inflammation. To make it to the injury site, leukocytes, most notably neutrophils, migrate along a gradient of chemokines that keeps growing. Additionally, neutrophils release a variety of pro-inflammatory cytokines which boost the inflammatory response [6]. Apoptosis, or necrosis, is followed by macrophage engulfment, or efferocytosis, to start the process of clearing out neutrophils. Neutrophphs must be eliminated quickly since their removal initiates the process of inflammation resolution [8]. The adaptive immune system includes activated regulatory T cells. Regulatory T cells, in addition to leukocytes, have the ability to reduce tissue inflammation by lowering the production of interferon-\(\gamma\) as well as the accumulation of proinflammatory macrophages. Macrophages are one of the significant factors in the progression from inflammation phase to proliferation. Pathogen-specific and damage-related molecular patterns activate macrophages. This causes their differentiation into the M1 subset, which is linked to phagocytic activity, scavenging, and also the synthesis of pro-inflammatory mediators, in the early stages of wound repair. Later, M1 changes into the M2 subset, displaying reparative characteristics.