Rational Design of Immunomodulatory Hydrogels for Chronic Wound Healing

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(39)

Published: July 12, 2021

With all the advances in tissue engineering for construction of fully functional skin tissue, complete regeneration chronic wounds is still challenging. Since immune reaction to damage critical regulating both quality and duration wound healing cascade, strategies modulate system are importance. Generally, response an injury, macrophages switch from pro-inflammatory anti-inflammatory phenotype. Therefore, controlling macrophages' polarization has become appealing approach regenerative medicine. Recently, hydrogels-based constructs, incorporated with various cellular molecular signals, have been developed utilized adjust cell functions stages healing. Here, current state knowledge on during first discussed. Recent advanced technologies used design immunomodulatory hydrogels then summarized. Rational providing controlled stimulation via hydrogel chemistry surface modification, as well incorporation molecules, also dicussed. In addition, effects hydrogels' properties immunogenic features process Finally, future directions upcoming research control responses highlighted.

Language: Английский

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Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 3, 2019

Abstract Tumor-associated macrophages (TAMs) usually express an M2 phenotype, which enables them to perform immunosuppressive and tumor-promoting functions. Reprogramming these TAMs toward M1 phenotype could thwart their pro-cancer activities unleash anti-tumor immunity, but efforts accomplish this are nonspecific elicit systemic inflammation. Here we describe a targeted nanocarrier that can deliver in vitro-transcribed mRNA encoding M1-polarizing transcription factors reprogram without causing toxicity. We demonstrate models of ovarian cancer, melanoma, glioblastoma infusions nanoparticles formulated with mRNAs interferon regulatory factor 5 combination its activating kinase IKKβ reverse the immunosuppressive, tumor-supporting state induces immunity promotes tumor regression. further establish nanoreagents safe for repeated dosing. Implemented clinic, immunotherapy enable physicians obviate suppressive tumors while avoiding treatments disrupt immune homeostasis.

Language: Английский

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The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 19, 2022

Innate and adaptive immunity represent a harmonic counterbalanced system involved in the induction, progression, possibly resolution of inflammatory reaction that characterize autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis (RA). Although immunopathophysiological mechanisms ARDs are not fully clarified, they often associated with an inappropriate macrophage/T-cell interaction, where classical (M1) or alternative (M2) macrophage activation may influence occurrence T-helper (Th)1 Th2 responses. In RA patients, M1/Th1 occurs environment dominated by Toll-like receptor (TLR) interferon (IFN) signaling, it promotes massive production pro-inflammatory cytokines [i.e., tumor necrosis factor-α (TNFα), interleukin (IL)-1, IL-12, IL-18, IFNγ], chemotactic factors, matrix metalloproteinases resulting osteoclastogenesis, erosion, progressive joint destruction. On other hand, M2/Th2 response determines release growth factors IL-4, IL-10, IL-13, transforming factor (TGF)-β] anti-inflammatory process leading to clinical remission RA. Several subtypes macrophages have been described. Five polarization states from M1 M2 confirmed vitro studies analyzing morphological characteristics, gene expression phenotype markers (CD80, CD86, TLR2, TLR4, CD206, CD204, CD163, MerTK), functional aspect, reactive oxygen species (ROS). An imbalance induce pathological consequences contribute several diseases, such as asthma osteoclastogenesis patients. addition, dynamic includes presence intermediate polarity stages distinguished specific surface production/release distinct molecules (i.e., nitric oxide, cytokines), which their state. This suggests "continuum" playing important role during inflammation its resolution. review discusses importance delicate M1/M2 different phases together identification pathways, cytokines, chemokines involved, outcomes The analysis these aspects could shed light on abnormal activation, novel therapeutical approaches restore balance.

Language: Английский

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Macrophages: The Good, the Bad, and the Gluttony

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 12, 2021

Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation. In this review, we will compile interpret recent findings on plasticity macrophages how these contribute to development non-infectious inflammatory diseases, with a particular focus allergic autoimmune disorders. The inflammation then be examined, emphasizing ability clear apoptotic immune cells. Rheumatoid arthritis (RA) is chronic autoimmune-driven spectrum diseases where persistent results synovial hyperplasia excessive cell accumulation, leading remodeling reduced function affected joints. central pathophysiology RA, driving episodic cycles tissue destruction. RA patients have increased numbers active M1 polarized pro-inflammatory few or inactive M2 type This imbalance macrophage homeostasis main contributor mediators resulting continual activation stromal populations accelerated remodeling. Modulation phenotype remains key therapeutic goal for treatment disease. Intriguingly, intervention glucocorticoids other DMARDs promotes re-polarization an anti-inflammatory phenotype; reprogramming dependent metabolic changes promote phenotypic switching. Allergic asthma associated Th2-polarised airway inflammation, structural large airways, hyperresponsiveness. Macrophage polarization has profound impact pathogenesis, as response allergen exposure regulated by intricate interplay between local factors including cytokines, chemokines danger signals from neighboring Th2-polarized environment characteristic asthma, high levels IL-4 produced locally infiltrating innate lymphoid helper T acquisition alternatively activated M2a macrophages, myriad effects structure. Targeting regulators currently being pursued diseases. re-balancing responses towards pro-resolution thus success response. It long been established apoptosis supports monocyte recruitment sites facilitating subsequent corpse clearance. drives mediates switch polarity macrophages. However, role cell-derived extracellular vesicles (ACdEV) control received remarkably little attention. ACdEV powerful intercellular communication, carrying wealth lipid protein may modulate phenotype, cargo immune-modulating enzymes. such interactions result repair disease different contexts. discuss origin, characterization, activity underlying mechanisms via clearance, order provide new insights into strategies could exploit capabilities agile responsive

Language: Английский

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The Role of Monocytes and Macrophages in Autoimmune Diseases: A Comprehensive Review

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: May 24, 2019

Monocytes (Mo) and macrophages (Mφ) are key components of the innate immune system involved in regulation initiation, development resolution many inflammatory disorders. In addition, these cells also play important immunoregulatory tissue-repairing roles to decrease reactions promote tissue regeneration. Several lines evidence have suggested a causal link between presence or activation autoimmune diseases. Mo Mφ infiltration diseased tissues is hallmark several However, detailed contributions cells, whether they actually initiate disease perpetuate progression, their phenotype functional alteration merely epiphenomena still unclear Additionally, little known about heterogeneous populations different Elucidating relevance diseases associated mechanisms could lead identification more effective therapeutic strategies future.

Language: Английский

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Immunological Approaches Towards Cancer and Inflammation: A Cross Talk

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: March 20, 2018

The inflammation is the protective response of body against various harmful stimuli, however, aberrant and inappropriate activation tends to become harmful. acute inflammatory resolved once offending agent subside but this becomes chronic in nature when unable successfully neutralized noxious stimuli. This microenvironment associated with release pro-inflammatory oncogenic mediators such as nitric oxide (NO), cytokines (IL-1β, IL-2, IL-6 TNF-α), growth factor chemokines. These make more vulnerable towards tumorigenesis. released during induce several molecular signaling cascades NF-κB, MAPKinase, Nrf2, Pi3K, JAK/STAT, Wnt/B-catenin, CREB. immune system its components have a pleiotropic effect on cancer progression. Immune T cells, NK macrophages, neutrophils either inhibit or enhance tumor initiation depending upon type cells involved. Tumor-associated macrophages (TAMs) tumor-associated (TANs) are pro-tumorigenic highly prevalent inflammation-mediated tumors. Similarly, presence regulatory (Treg) an setting suppresses system, thus paving way for oncogenesis. However, Treg also autoimmune inflammation. In contrast, cytotoxic helper confer anti-tumor immunity better prognosis patients cancer. Cytotoxic inflict direct expressing markers. Currently, anti-inflammatory therapies under trials which these exploited. Adoptive cell transfer (ACT) comprised infiltrating lymphocytes (TILs) has been tried treatment tumors after their ex vivo expansion. Mediators by tumorigenic cross talk nearby promoting inhibiting Recently, cytokine-based being developed trial treat types manifestations. Monoclonal antibodies directed TNF-α, VEGF, shown promising results ameliorate cancer, while administration IL-2 cause regression.

Language: Английский

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Drug delivery to macrophages: A review of targeting drugs and drug carriers to macrophages for inflammatory diseases

Advanced Drug Delivery Reviews, Journal Year: 2019, Volume and Issue: 165-166, P. 15 - 40

Published: Dec. 6, 2019

Language: Английский

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Myeloperoxidase: A new player in autoimmunity

Cellular Immunology, Journal Year: 2017, Volume and Issue: 317, P. 1 - 8

Published: May 11, 2017

Language: Английский

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M1/M2 macrophages and their overlaps – myth or reality?

Clinical Science, Journal Year: 2023, Volume and Issue: 137(15), P. 1067 - 1093

Published: Aug. 1, 2023

Abstract Macrophages represent heterogeneous cell population with important roles in defence mechanisms and homoeostasis. Tissue macrophages from diverse anatomical locations adopt distinct activation states. M1 M2 are two polarized forms of mononuclear phagocyte vitro differentiation phenotypic patterns functional properties, but vivo, there is a wide range different macrophage phenotypes between depending on the microenvironment natural signals they receive. In human infections, pathogens use strategies to combat these include shaping polarization towards one or another phenotype. infiltrating tumours can affect patient’s prognosis. have been shown promote tumour growth, while provide both tumour-promoting anti-tumour properties. autoimmune diseases, prolonged activation, as well altered function contribute their onset activity. atherosclerotic lesions, expressing profiles detected potential factors affecting occurrence cardiovascular diseases. allergic inflammation, T2 cytokines drive profiles, which airway inflammation remodelling. transplantations seem acute rejection, fibrosis graft. The view pro-inflammatory suppressing seems be an oversimplification because cells exploit very high level plasticity large scale immunophenotypes overlapping this respect, it would more precise describe M1-like M2-like.

Language: Английский

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Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches

Bioactive Materials, Journal Year: 2020, Volume and Issue: 6(1), P. 244 - 261

Published: Aug. 22, 2020

A coordinated interaction between osteogenesis and osteoimmune microenvironment is essential for successful bone healing. In particular, macrophages play a central regulatory role in all stages of repair. Depending on the signals they sense, these highly plastic cells can mediate host immune response against exterior molecular stimuli implanted scaffolds, to exert regenerative potency varying extent. this article, we first encapsulate immunomodulatory functions during regeneration into three aspects, as sweeper, mediator instructor. We introduce phagocytic different healing periods ('sweeper') overview variety paracrine cytokines released by either mediating cell mobilisation, vascularisation matrix remodelling ('mediator'), or directly driving osteogenic differentiation progenitors repair ('instructor'). Then, systematically classify discuss emerging engineering strategies recruit, activate modulate phenotype transition macrophages, exploit power endogenous enhance performance engineered tissue.

Language: Английский

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