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      Harnessing strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns

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          Abstract

          Diabetic wound is a great threat to patient's health and lives. The refractory diabetic wound shows spatial inflammation patterns, in which the early-wound pattern depicts a deprived acute inflammatory response, and the long-term non-healing wound pattern delineates an excessive and persistent inflammation due to the delayed immune cell infiltration in a positive feedback loop. In this work, we give points to some strategies to normalize the dysregulated immune process based on the spatial inflammation pattern differences in diabetic wound healing. First of all, inhibiting inflammatory response to avoid subsequent persistent and excessive immune infiltration for the early diabetic wound is proposed. However, diabetic wounds are unperceptive trauma that makes patients miss the best treatment time. Therefore, we also introduce two strategies for the long-term non-healing diabetic wound. One strategy is about changing chronic wounds to acute ones, which aims to rejuvenate M1 macrophages in diabetic wounds and make spontaneous M2 polarization possible. To activate the controllable proinflammatory response, western medicine delivers proinflammatory molecules while traditional Chinese medicine develops “wound-pus promoting granulation tissue growth theory”. Another strategy to solve long-term non-healing wounds is seeking switches that target M1/M2 transition directly. These investigations draw a map that delineates strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns systematically.

          Highlights

          • Diabetic wounds are hard-to-heal that need smart strategies to expedite the healing process.

          • Diabetic wound healing shows spatial inflammation patterns in different timeline.

          • We give points to strategies for enhancing diabetic wound healing based on spatial inflammation patterns.

          • These strategies give inspirations to advance precision medicine for diabetic wounds.

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          Most cited references126

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          Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis

          The use of extracellular vesicles, specifically exosomes, as carriers of biomarkers in extracellular spaces has been well demonstrated. Despite their promising potential, the use of exosomes in the clinical setting is restricted due to the lack of standardization in exosome isolation and analysis methods. The purpose of this review is to not only introduce the different types of extracellular vesicles but also to summarize their differences and similarities, and discuss different methods of exosome isolation and analysis currently used. A thorough understanding of the isolation and analysis methods currently being used could lead to some standardization in the field of exosomal research, allowing the use of exosomes in the clinical setting to become a reality.
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            Modulation of macrophage phenotype by cell shape.

            Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Although much is known about how soluble factors influence macrophage polarization, relatively little is known about how physical cues present in the extracellular environment might modulate proinflammatory (M1) vs. prohealing (M2) activation. Specifically, the role of cell shape has not been explored, even though it has been observed that macrophages adopt different geometries in vivo. We and others observed that macrophages polarized toward different phenotypes in vitro exhibit dramatic changes in cell shape: M2 cells exhibit an elongated shape compared with M1 cells. Using a micropatterning approach to control macrophage cell shape directly, we demonstrate here that elongation itself, without exogenous cytokines, leads to the expression of M2 phenotype markers and reduces the secretion of inflammatory cytokines. Moreover, elongation enhances the effects of M2-inducing cytokines IL-4 and IL-13 and protects cells from M1-inducing stimuli LPS and IFN-γ. In addition shape- but not cytokine-induced polarization is abrogated when actin and actin/myosin contractility are inhibited by pharmacological agents, suggesting a role for the cytoskeleton in the control of macrophage polarization by cell geometry. Our studies demonstrate that alterations in cell shape associated with changes in ECM architecture may provide integral cues to modulate macrophage phenotype polarization.
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              Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?

              Neutrophils are the most abundant leukocytes in the circulation, and have been regarded as first line of defense in the innate arm of the immune system. They capture and destroy invading microorganisms, through phagocytosis and intracellular degradation, release of granules, and formation of neutrophil extracellular traps after detecting pathogens. Neutrophils also participate as mediators of inflammation. The classical view for these leukocytes is that neutrophils constitute a homogenous population of terminally differentiated cells with a unique function. However, evidence accumulated in recent years, has revealed that neutrophils present a large phenotypic heterogeneity and functional versatility, which place neutrophils as important modulators of both inflammation and immune responses. Indeed, the roles played by neutrophils in homeostatic conditions as well as in pathological inflammation and immune processes are the focus of a renovated interest in neutrophil biology. In this review, I present the concept of neutrophil phenotypic and functional heterogeneity and describe several neutrophil subpopulations reported to date. I also discuss the role these subpopulations seem to play in homeostasis and disease.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                31 May 2023
                October 2023
                31 May 2023
                : 28
                : 243-254
                Affiliations
                [a ]Key Laboratory for Ultrafine Materials of Ministry of Education, School of Material Science and Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, China
                [b ]Wenzhou Institute of Shanghai University, Wenzhou, 325000, China
                [c ]Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai, 200237, China
                Author notes
                []Corresponding author. East China University of Science and Technology, No 130, Meilong Road, Shanghai, China. quxue@ 123456ecust.edu.cn
                Article
                S2452-199X(23)00138-X
                10.1016/j.bioactmat.2023.04.019
                10245071
                37292231
                61a27e39-0601-48e8-98cc-b71f24eb1ade
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 18 February 2023
                : 17 April 2023
                : 20 April 2023
                Categories
                Review Article

                diabetic wound,spatial inflammation pattern,m1/m2 transition,biomaterials

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