Macrophage-mediated inflammation in diabetic wound repair

Wolf, Sonya; Melvin, William J.; Gallagher, Katherine A.

doi:10.1016/j.semcdb.2021.06.013

Cited by 87 publications

(59 citation statements)

References 104 publications

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“…Macrophages are one of the key cells that regulate the wound repair process [14,15]. Wounds without macrophages have delayed re-epithelialisation, impaired angiogenesis, reduced collagen deposition, and reduced cell proliferation [16].…”

Section: There Is a Clinical And Economic Need For Better Wound Therapiesmentioning

confidence: 99%

“…Wounds without macrophages have delayed re-epithelialisation, impaired angiogenesis, reduced collagen deposition, and reduced cell proliferation [16]. They are not a homogenous population of cells and several different combinations of phenotypes with distinct functions present at different times in the repair process [14,17,18]. Macrophage function is altered in people with diabetes such that they have a reduced capacity to clear an infection and their function in the later stages of repair is altered, leading to a delay in the repair process [14,[19][20][21][22][23].…”

Section: There Is a Clinical And Economic Need For Better Wound Therapiesmentioning

confidence: 99%

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

et al. 2021

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Macrophages play a prominent role in wound healing. In the early stages, they promote inflammation and remove pathogens, wound debris, and cells that have apoptosed. Later in the repair process, they dampen inflammation and secrete factors that regulate the proliferation, differentiation, and migration of keratinocytes, fibroblasts, and endothelial cells, leading to neovascularisation and wound closure. The macrophages that coordinate this repair process are complex: they originate from different sources and have distinct phenotypes with diverse functions that act at various times in the repair process. Macrophages in individuals with diabetes are altered, displaying hyperresponsiveness to inflammatory stimulants and increased secretion of pro-inflammatory cytokines. They also have a reduced ability to phagocytose pathogens and efferocytose cells that have undergone apoptosis. This leads to a reduced capacity to remove pathogens and, as efferocytosis is a trigger for their phenotypic switch, it reduces the number of M2 reparative macrophages in the wound. This can lead to diabetic foot ulcers (DFUs) forming and contributes to their increased risk of not healing and becoming infected, and potentially, amputation. Understanding macrophage dysregulation in DFUs and how these cells might be altered, along with the associated inflammation, will ultimately allow for better therapies that might complement current treatment and increase DFU’s healing rates.

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Section: There Is a Clinical And Economic Need For Better Wound Therapiesmentioning

confidence: 99%

Section: There Is a Clinical And Economic Need For Better Wound Therapiesmentioning

confidence: 99%

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

et al. 2021

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“…Neutrophil recruitment promotes the production of more NETs and activates the release of NLRP3 inflammatory bodies and IL-1b of macrophages through the TLR-4/TLR-9/NF-kB signal pathway (160). Although a large number of pro-inflammatory M1 macrophages are activated, phagocytosis of apoptotic neutrophils by these macrophages is inhibited, resulting in a disturbance in the process of macrophage polarization (161)(162)(163). With increase in the number of degranulated mast cells, a sustained inflammatory response is eventually achieved (164).…”

Section: Cell-cell and Cell-ecm Interactionsmentioning

confidence: 99%

“…The inflammatory cascade continues to cause the activation and accumulation of T cells, especially that of Th17 cells. Th17 cells secrete IL-17 to maintain the activity of M1 macrophages, leading to persistent inflammatory wound healing ( 162 ). On the contrary, increasing the number of LCs in the wound of diabetic mice has been shown to improve healing ( 165 ).…”

Section: Cell-cell and Cell-ecm Interactionsmentioning

confidence: 99%

“…A large number of pro-inflammatory factors increased the release of MMPs and accelerated the degradation of the ECM, which further reduced the proliferation and collagen deposition of fibroblasts ( 4 , 166 ). In this pathological inflammatory microenvironment, inflammatory genes expressed by fibroblasts are up-regulated and keratinocytes release IL-1α and type I interferon, triggering an inflammatory chain reaction in adjacent stromal cells ( 92 , 162 ). This, in turn, promotes the flow of immune cells into the injured site.…”

Section: Cell-cell and Cell-ecm Interactionsmentioning

confidence: 99%

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Inflammatory Microenvironment of Skin Wounds

et al. 2022

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Wound healing is a dynamic and highly regulated process that can be separated into three overlapping and interdependent phases: inflammation, proliferation, and remodelling. This review focuses on the inflammation stage, as it is the key stage of wound healing and plays a vital role in the local immune response and determines the progression of wound healing. Inflammatory cells, the main effector cells of the inflammatory response, have been widely studied, but little attention has been paid to the immunomodulatory effects of wound healing in non-inflammatory cells and the extracellular matrix. In this review, we attempt to deepen our understanding of the wound-healing microenvironment in the inflammatory stage by focusing on the interactions between cells and the extracellular matrix, as well as their role in regulating the immune response during the inflammatory stage. We hope our findings will provide new ideas for promoting tissue regeneration through immune regulation.

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Advanced Biomaterials for Regulating Polarization of Macrophages in Wound Healing

Mao

Chen

Cai

et al. 2021

Adv Funct Materials

120

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Macrophage immunotherapy is an emerging treatment strategy that modulates the immune system to promote wound healing. The functionality and regeneration of tissue depend on spatially and temporally regulating the biophysical and biochemical microenvironmental with poorly understood mechanisms. Biomaterials are carefully crafted to display and deliver macrophage regulatory signals in a precise and near‐physiological way, serving as powerful artificial microenvironments in which to explore and direct the fate of macrophages. The review starts with discussing the classification and function of macrophages, and then introduces the polarization of macrophages in different microenvironments of conventional wounds and chronic wounds. Recent advances in biomaterials that balance the phenotypes of macrophages in wound healing are emphasized. Finally, looking ahead, the potential ability of biomaterial scaffolds to modulate immune signaling to produce an environment conducive to regeneration is discussed.

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Macrophage-mediated inflammation in diabetic wound repair

Cited by 87 publications

References 104 publications

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

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

Inflammatory Microenvironment of Skin Wounds

Advanced Biomaterials for Regulating Polarization of Macrophages in Wound Healing

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