When one sustains a cut from hitting debris, the epidermis and the dermis get damaged together with the underlying blood vessels. The wound's healing process will take four phases; Hemostasis (stopping the bleeding), Inflammation, proliferation, and remodeling for the wound to completely heal. During the hemostasis phase, platelets help in the formation of clots. The platelets aggregate around the injured area and initiate the clotting process, which prevents additional blood loss and forms a temporal coverage that protects the wound from the external environment. Moreover, during the clotting, the platelets secrete stimuli that summon other immune cells, which initiate the inflammatory process (Caicedo & Devesa, 2018) . The hemostasis phase results in redness and swelling primarily due to the dilation of local blood cells that paves the way for immune cells to get to the injured area. Neutrophils cell are the first responders who help in cleaning the wound from foreign materials and bacteria. The monocyte cells are mobilized and differentiated into a white blood cell called macrophages, which participates in the healing process. The macrophages clean the injured area of all debris and lay the foundation for tissue remodeling and repair. As the name suggested, macrophages use their eating ability to clean the cut and shift to tissue repair in the proliferative stage.
During the proliferative phase, macrophages help in tissue's extracellular matrix reconstruction by producing a growth factor called fibroblasts. Fibroblasts' growth factor leads to the growth of extracellular matrix repair cells called fibroblasts. The fibroblasts are differentiated into myofibroblasts that close the cut through contracting, similar to muscle cells. Such causes a permanent closure of the cut and prevents the would external environment exposure. New blood vessels are formed through guidance from macrophages in the angiogenesis process. Secretion of Vascular Endothelial Growth Factor and Transforming Growth Factor by macrophage recruits cells that form the new blood vessels and then draw their growth pattern (Hiller-Sturmhöfel & Bartke, 1998) . During this healing process, one may experience stretching and itching. After healing of the wound that takes a couple of days, a scar is left due to the skin's scaffolding. The wounded area does not retain its original strength due to the various activities in the wound healing process.
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During wound healing, communication between cells is very vital to speed up the process. However, the body has two main parts used for relatively long-distance communication: the endocrine and nervous systems. The two systems play a major role in maintaining homeostasis in the body and include injury response. The nervous system utilizes chemical and electrical signaling types of intercellular communication (Riege et al., 2016). Such can be a direct action of electrical potential or action through a chemical that acts rapidly and locally. After the electrical signal arrives at the synaptic terminal in the form of the action potential, they diffuse through the synaptic cleft, which then binds with the receptor cells inducing a stimulation that triggers a response from this receiving cell. The target cells respond so quickly and cease immediately after the neural signaling ends. Therefore, neurotransmitters only require body functions that require quick and very brief actions.
In contrast, endocrine systems use only chemical signaling as a mode of communication. These signals initiated by the endocrine organs cause a release of a chemical hormone transported by blood and spread throughout the body, where there interact with receptors cells triggering a response. Therefore, endocrine signaling requires a longer response time compared to neural signaling.
The four healing phases involve several neurotransmitters and hormones that regulate the cistrome, transcriptome, miRNAome, and proteome required to heal an injury properly. During the initial stage of hemostasis, injured platelets and keratinocytes release interleukin and growth factor that primarily attracts neutrophils, which stimulates the secretion of growth factors from the neighboring cells. The nerve ending apposed to the skin and the sensory fibers activates the keratinocytes, which are derived inflammatory cytokines by the help of a gene-related peptide known as calcitonin and a neurotransmitter substance P. The uptake and clearance of the phagocytic cellular, which is done by the keratinocytes found in the epidermis, is considered a protective mechanism against various injury-induced stimuli. The TGF-β derived from the keratinocyte and the platelets and ECM protein adherence trigger the conversion of monocytes that are used to activate the macrophages at the damaged area, which causes the formation of granulation tissues also helps in the secreting of growth factor and the cytokines the enhancing angiogenesis. The epithelialization of cuts after an injury involves keratinocyte proliferation. Sensory nerves enhance the re-epithelialization process by utilizing vasoactive internal peptide, which is a neuropeptide that takes part in the activation of keratinocyte migration. A newly integrin receptor formed on the epidermal cells pass a series of phenotypic changes that bind with several ECM competitors, such as fibronectin attached in the cut injury and the clot. The growth factors such as growth hormones such as epidermal growth factor, the TGF-α stimulate re-epithelialization. The granulation tissues formed at this stage consist of capillaries that start to take the injury space. The macrophages that generate the PDGF and TGF-β1 takes a huge role in fibroplasia and angiogenesis stimulation. Fibroblasts secrete a growth hormone that plays a key benefits role in the closure of a wound and granulation tissue formation.
References
Caicedo, D., & Devesa, J. (2018, November 30). Growth Hormone (GH) and Wound Healing. doi:10.5772/intechopen.80978
Hiller-Sturmhöfel, S., & Bartke, A. (1998). The endocrine system: an overview. Alcohol Health Res World . Retrieved from https://pubmed.ncbi.nlm.nih.gov/15706790/
Rieger, S., Zhao, H., Martin, P., Abe, K., & Lisse, T. S. (2016, January 1). The role of nuclear hormone receptors in cutaneous wound repair. HHS Public Access . doi:10.1002/cbf.3086
