Macrophages in immunoregulation and therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 22, 2023

Abstract Macrophages exist in various tissues, several body cavities, and around mucosal surfaces are a vital part of the innate immune system for host defense against many pathogens cancers. possess binary M1/M2 macrophage polarization settings, which perform central role an array tasks via intrinsic signal cascades and, therefore, must be precisely regulated. Many crucial questions about signaling modulation yet to uncovered. In addition, clinical importance tumor-associated macrophages is becoming more widely recognized as significant progress has been made understanding their biology. Moreover, they integral tumor microenvironment, playing regulation wide variety processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis, immunosuppression, resistance chemotherapeutic checkpoint blockade immunotherapies. Herein, we discuss signaling, mechanical stresses modulation, metabolic pathways, mitochondrial transcriptional, epigenetic regulation. Furthermore, have broadly extended traps essential roles autophagy aging regulating functions. discussed recent advances macrophages-mediated autoimmune diseases tumorigenesis. Lastly, targeted therapy portray prospective targets therapeutic strategies health diseases.

Язык: Английский

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Magnetically Driven Micro and Nanorobots

Chemical Reviews, Год журнала: 2021, Номер 121(8), С. 4999 - 5041

Опубликована: Март 31, 2021

Manipulation and navigation of micro nanoswimmers in different fluid environments can be achieved by chemicals, external fields, or even motile cells. Many researchers have selected magnetic fields as the active actuation source based on advantageous features this strategy such remote spatiotemporal control, fuel-free, high degree reconfigurability, programmability, recyclability, versatility. This review introduces fundamental concepts advantages micro/nanorobots (termed here "MagRobots") well basic knowledge materials, setups for manipulation, field configurations, symmetry-breaking strategies effective movement. These are discussed to describe interactions between fields. Actuation mechanisms flagella-inspired MagRobots (i.e., corkscrew-like motion traveling-wave locomotion/ciliary stroke motion) surface walkers surface-assisted motion), applications other propulsion approaches, stimulation beyond provided followed fabrication techniques (quasi-)spherical, helical, flexible, wire-like, biohybrid MagRobots. Applications targeted drug/gene delivery, cell minimally invasive surgery, biopsy, biofilm disruption/eradication, imaging-guided delivery/therapy/surgery, pollution removal environmental remediation, (bio)sensing also reviewed. Finally, current challenges future perspectives development magnetically powered miniaturized motors discussed.

Язык: Английский

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Polydopamine-mediated graphene oxide and nanohydroxyapatite-incorporated conductive scaffold with an immunomodulatory ability accelerates periodontal bone regeneration in diabetes

Bioactive Materials, Год журнала: 2022, Номер 18, С. 213 - 227

Опубликована: Март 22, 2022

Regenerating periodontal bone tissues in the aggravated inflammatory microenvironment under diabetic conditions is a great challenge. Here, polydopamine-mediated graphene oxide (PGO) and hydroxyapatite nanoparticle (PHA)-incorporated conductive alginate/gelatin (AG) scaffold developed to accelerate regeneration by modulating microenvironment. PHA confers with osteoinductivity PGO provides pathway for scaffold. The promotes transferring endogenous electrical signals cells activating Ca2+ channels. Moreover, nanomaterials has reactive oxygen species (ROS)-scavenging ability anti-inflammatory activity. It also exhibits an immunomodulatory that suppresses M1 macrophage polarization activates M2 macrophages secrete osteogenesis-related cytokines mediating glycolytic RhoA/ROCK pathways macrophages. induces excellent defects of rats because synergistic effects good conductive, ROS-scavenging, anti-inflammatory, abilities. This study fundamental insights into synergistical conductivity, osteoinductivity, abilities on offers novel strategy design biomaterials treatment immune-related diseases tissue regeneration.

Язык: Английский

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Self‐Healing Hydrogel Embodied with Macrophage‐Regulation and Responsive‐Gene‐Silencing Properties for Synergistic Prevention of Peritendinous Adhesion

Advanced Materials, Год журнала: 2021, Номер 34(5)

Опубликована: Ноя. 24, 2021

Antiadhesion barriers such as films and hydrogels used to wrap repaired tendons are important for preventing the formation of adhesion tissue after tendon surgery. However, sliding can compress adjacent hydrogel barrier cause it rupture, which may then lead unexpected inflammation. Here, a self-healing deformable hyaluronic acid (HA) is constructed peritendinous antiadhesion barrier. Matrix metalloproteinase-2 (MMP-2)-degradable gelatin-methacryloyl (GelMA) microspheres (MSs) encapsulated with Smad3-siRNA nanoparticles entrapped within HA inhibit fibroblast proliferation prevent adhesion. GelMA MSs responsively degraded by upregulation MMP-2, achieving on-demand release siRNA nanoparticles. Silencing effect around 75% toward targeted gene. Furthermore, shows relatively attenuated inflammation compared non-healing hydrogel. The mean scores composite group 1.67 ± 0.51 2.17 0.75 macroscopic histological evaluation, respectively. proposed MMP-2-responsive drug behavior highly effective decreasing inhibiting Therefore, this research provides new strategy development safe barriers.

Язык: Английский

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Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Янв. 10, 2022

Abstract Immune response and new tissue formation are important aspects of repair. However, only a single aspect is generally considered in previous biomedical interventions, the synergistic effect unclear. Here, dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn 2+ ) osteoinductive growth factors BMP-2 peptide) designed via mussel adhesion-mediated ion coordination molecular clicking strategy. Compared to bare TiO 2 group, can increase M2 macrophage recruitment by up 92.5% vivo upregulate expression cytokine IL-10 84.5%; while peptide macrophages 124.7% 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) bone ingrowth (82.1%) compared (98.6 N 45.1%, respectively). Taken together, be utilized synergistically modulate osteoimmune microenvironment at interface, enhancing regeneration for successful implantation.

Язык: Английский

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Bioengineered nanogels for cancer immunotherapy

Chemical Society Reviews, Год журнала: 2022, Номер 51(12), С. 5136 - 5174

Опубликована: Янв. 1, 2022

Recent years have witnessed increasingly rapid advances in nanocarrier-based biomedicine aimed at improving treatment paradigms for cancer. Nanogels serve as multipurpose and constructed vectors formed via intramolecular cross-linking to generate drug delivery systems, which is attributed predominantly their satisfactory biocompatibility, bio-responsiveness, high stability, low toxicity. Recently, immunotherapy has experienced unprecedented growth become the preferred strategy cancer treatment, mainly involves mobilisation of immune system an enhanced anti-tumour immunity tumour microenvironment. Despite inspiring success, immunotherapeutic strategies are limited due response rates immune-related adverse events. Like other nanomedicines, nanogels comparably by lower focal enrichment upon introduction into organism injection. Because three-dimensional cross-linked aqueous materials that exhibit similar properties natural tissues structurally stable, they can comfortably cope with shear forces serum proteins bloodstream, longer circulation life increases chance nanogel accumulation tumour, conferring deep penetration. The large specific surface area reduce or eliminate off-target effects introducing stimuli-responsive functional groups, allowing multiple physical chemical modifications purposes improve targeting cell subpopulations organs, increasing bioavailability drug, a events on therapies. slow release reaching site facilitates long-term awakening host's system, ultimately achieving therapeutic effects. As effective candidate immunotherapy, nanogel-based been widely used. In this review, we summarize recent deliver immunomodulatory small molecule drugs, antibodies, genes cytokines, target antigen presenting cells, form vaccines, enable chimeric receptor (CAR)-T therapy. Future challenges well expected feasible prospects clinical also highlighted.

Язык: Английский

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Immunomodulatory bioactive glasses for tissue regeneration

Acta Biomaterialia, Год журнала: 2021, Номер 133, С. 168 - 186

Опубликована: Авг. 18, 2021

The regulatory functions of the immune response in tissue healing, repair, and regeneration have been evidenced last decade. Immune cells play central roles responses toward inducing favorable regenerative processes. Modulating controlling cell (particularly macrophages) is an emerging approach to enhance regeneration. Bioactive glasses (BGs) are multifunctional materials exhibiting osteogenic, angiogenic, antibacterial properties, being increasingly investigated for various scenarios, including bone wound healing. On other hand, immunomodulatory effects BGs relation regenerating tissues started be understood, key knowledge emerging. This first review article summarizing repair firstly introduced, discussing potential mechanisms regarding immunomodulation induced by BGs. Moreover, interactions between involved process (dissolution products) summarized detail. Particularly, a well-regulated timely switch macrophage phenotype from pro-inflammatory anti-inflammatory crucial constructive through modulating osteogenesis, osteoclastogenesis, angiogenesis. influence BG characteristics on discussed. We highlight strategies employed harness enhanced regeneration, incorporation active ions, surface functionalization, controlled release molecules. Finally, we conclude with our perspectives future research challenges directions field Immunomodulatory bioactive healing understood. summarize those studies which focused introduce Interactions processes (and their dissolution products, biologically ions) elaborated. modulate enhancing agents. outlining anticipate that increasing efforts will start emerge area

Язык: Английский

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Down-Regulating Scar Formation by Microneedles Directly via a Mechanical Communication Pathway

ACS Nano, Год журнала: 2022, Номер 16(7), С. 10163 - 10178

Опубликована: Май 26, 2022

Excessive extracellular matrix deposition drives fibroblasts into a state of high mechanical stress, exacerbating pathological fibrosis and hypertrophic scar formation, leading to tissue dysfunction. This study reports minimally invasive convenient approach obtaining scarless using silk fibroin microneedle patch (SF MNs). We found that by tuning the MN size density only, biocompatible MNs significantly decreased elevation index in rabbit ear model increased ultimate tensile strength close regular skin. To advance our understanding this recent approach, we built fibroblast-populated collagen lattice system finite element MN-mediated cellular behavior fibroblasts. reduced generated contraction as indicated expression sensitive gene ANKRD1. Specifically, SF attenuated integrin-FAK signaling consequently down-regulated TGF-β1, α-SMA, I, fibronectin. It resulted low-stress microenvironment helps reduce formation significantly. Microneedles' physical intervention

Язык: Английский

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Advanced surface engineering of titanium materials for biomedical applications: From static modification to dynamic responsive regulation

Bioactive Materials, Год журнала: 2023, Номер 27, С. 15 - 57

Опубликована: Март 27, 2023

Titanium (Ti) and its alloys have been widely used as orthopedic implants, because of their favorable mechanical properties, corrosion resistance biocompatibility. Despite significant success in various clinical applications, the probability failure, degradation revision is undesirably high, especially for patients with low bone density, insufficient quantity or osteoporosis, which renders studies on surface modification Ti still active to further improve results. It discerned that physicochemical properties directly influence even control dynamic interaction subsequently determines rejection implants. Therefore, it crucial endow bulk materials specific high bioactivity can be performed by realize osseointegration. This article first reviews characteristics conventional techniques involving mechanical, physical chemical treatments based formation mechanism modified coatings. Such methods are able but surfaces static state cannot respond biological cascades from living cells tissues. Hence, beyond traditional design, responsive avenues then emerging. The stimuli sources functionalization originate environmental triggers physiological triggers. In short, this review surveys recent developments engineering materials, a emphasis advances functionality, provides perspectives improving biocompatibility

Язык: Английский

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Multi-functional wound dressings based on silicate bioactive materials

Biomaterials, Год журнала: 2022, Номер 287, С. 121652 - 121652

Опубликована: Июнь 28, 2022

Язык: Английский

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