Immunology of Acute and Chronic Wound Healing

Abstract

Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.

Single Snapshot Imaging of Optical Properties (SSOP) for Perfusion Assessment during Gastric Conduit Creation for Esophagectomy: An Experimental Study on Pigs

“…However, persistent inflammation led to excessive quantities of pro-inflammatory macrophages, whereas the number of macrophages with anti-inflammatory phenotypes became lower. As a result, the establishment of a highly inflammatory environment with an overabundance of inflammatory mediators promotes the degradation of the extracellular matrix, preventing anastomotic healing [ 42 ].…”

Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds

“…In the inflammatory phase, a number of immune cells, including tissue resident macrophages, and neutrophils and monocytes recruited to the site of injury from the blood, work with numerous cell types in and surrounding the injured skin to orchestrate the repair process [ 27 , 28 ]. This occurs through a combination of the actions of these cells themselves, their signalling pathways, and through the release of their soluble mediators, such as cytokines, chemokines, growth factors, and metabolites that signal other cells to perform specific tasks, to produce the final newly formed tissue [ 24 ].…”

“…To accommodate the recruitment of a significant number of monocyte cells from the blood, there is an increase in myeloid lineage committed multipotent progenitors and monocytes in bone marrow that results in a 70% increase in monocytes in circulation on day 2, with their levels returning to steady-state levels after around day 4 [ 30 , 38 ]. These monocytes are classified as either classical/pro-inflammatory monocytes that are CD14 + CD16 − capable of differentiating into pro-inflammatory M1 macrophages or anti-inflammatory monocytes that are CD14 low /CD16 + that give rise to mostly M2 macrophages [ 27 ]. In mouse models of wound repair, circulating monocytes can also be divided into two groups: CX3CR1 low CCR2 + Ly6C + and CX3CR1 high CCR2 − Ly6C − [ 15 ].…”

“…This increase in diversity leads to an upregulation in host genes in the wound tissue related to inflammation when compared to mild to moderate DFI gene levels, while genes related to epithelial—mesenchymal transition, which are required for the wound to close, are reduced [ 62 ]. Thus, it appears that the number and diversity of infecting organisms can alter the host immune response [ 27 ]. Whether this change in host response is coming from the already altered macrophage response in these wounds is not clear.…”

Immunomodulatory Properties of Host Defence Peptides in Skin Wound Healing

“…Furthermore, high levels of hBD-2 and hBD-3 detected at wound sites promote keratinocyte migration and proliferation, indicating their involvement in the re-epithelialization of the healing epithelium [95,112]. A relatively recent study demonstrated that topical insulin delivery to the wound enhanced the levels of extracellular-signal regulated kinase (ERK) and protein kinase B (Akt) [113].…”