3D GelMA ICC Scaffolds Combined with SW033291 for Bone Regeneration by Modulating Macrophage Polarization

Despite the interaction between bone marrow mesenchymal stem cells (BMSCs) and macrophages has been found to play a critical role in repairing bone defects, it remains a challenge to develop a desirable tissue engineering scaffold for synchronous regulation of osteogenic differentiation and macrophage polarization. Herein, this study proposed a novel strategy to treat bone defects based on three-dimensional Gelatin Methacryloyl Inverted Colloidal Crystal (3D GelMA ICC) scaffold and an active 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor SW033291. Specifically, the 3D GelMA ICC scaffolds were firstly prepared by colloidal templating method, which displayed good cell attachment and promoted intercellular interaction among macrophage and BMSCs due to its uniform pore interconnectivity. By combined use of SW033291, the release of Prostaglandin E2 (PGE2) from BMSCs on the GelMA ICC scaffold was significantly upregulated and macrophages M2 polarization was markedly increased. In turn, BMSCs proliferation and osteogenic differentiation was further enhanced by paracrine regulation of M2 macrophage, and thus finally caused more in vivo new bone formation by shaping up a pro-regenerative local immune microenvironment surrounding GelMA ICC scaffold. Our findings demonstrate the potential of 3D GelMA ICC scaffolds combined with SW033291 to become an effective tissue engineering strategy for bone regeneration.

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Sinusoidal electromagnetic fields accelerate bone regeneration by boosting the multifunctionality of bone marrow mesenchymal stem cells

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02302-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Weigang Li ◽

Wenbin Liu ◽

Wei Wang ◽

Jiachen Wang ◽

Tian Ma ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Regeneration ◽

Electromagnetic Fields ◽

Bone Defects ◽

Cell Scaffolds ◽

Marrow Mesenchymal Stem Cells ◽

Calvarial Defects

Abstract Background The repair of critical-sized bone defects is always a challenging problem. Electromagnetic fields (EMFs), used as a physiotherapy for bone defects, have been suspected to cause potential hazards to human health due to the long-term exposure. To optimize the application of EMF while avoiding its adverse effects, a combination of EMF and tissue engineering techniques is critical. Furthermore, a deeper understanding of the mechanism of action of EMF will lead to better applications in the future. Methods In this research, bone marrow mesenchymal stem cells (BMSCs) seeded on 3D-printed scaffolds were treated with sinusoidal EMFs in vitro. Then, 5.5 mm critical-sized calvarial defects were created in rats, and the cell scaffolds were implanted into the defects. In addition, the molecular and cellular mechanisms by which EMFs regulate BMSCs were explored with various approaches to gain deeper insight into the effects of EMFs. Results The cell scaffolds treated with EMF successfully accelerated the repair of critical-sized calvarial defects. Further studies revealed that EMF could not directly induce the differentiation of BMSCs but improved the sensitivity of BMSCs to BMP signals by upregulating the quantity of specific BMP (bone morphogenetic protein) receptors. Once these receptors receive BMP signals from the surrounding milieu, a cascade of reactions is initiated to promote osteogenic differentiation via the BMP/Smad signalling pathway. Moreover, the cytokines secreted by BMSCs treated with EMF can better facilitate angiogenesis and osteoimmunomodulation which play fundamental roles in bone regeneration. Conclusion In summary, EMF can promote the osteogenic potential of BMSCs and enhance the paracrine function of BMSCs to facilitate bone regeneration. These findings highlight the profound impact of EMF on tissue engineering and provide a new strategy for the clinical treatment of bone defects.

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Osteon-mimetic 3D nanofibrous scaffold enhancing stem cell proliferation and osteogenic differentiation for bone regeneration

Biomaterials Science ◽

10.1039/d1bm01489g ◽

2022 ◽

Author(s):

Ting Song ◽

Jianhua Zhou ◽

Ming Shi ◽

Liuyang Xuan ◽

Huamin Jiang ◽

...

Keyword(s):

Tissue Engineering ◽

Cell Proliferation ◽

Stem Cell ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Nanofibrous Scaffold ◽

Hierarchical Microstructure ◽

Stem Cell Proliferation

Scaffold microstructure is important for bone tissue engineering. Failure to synergistically imitate the hierarchical microstructure of bone component, such as osteon with concentric multilayers assembled by nanofibers, hindered the performance...

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The effect of the WKYMVm peptide on promoting mBMSC secretion of exosomes to induce M2 macrophage polarization through the FPR2 pathway

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02321-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Wenbo Zhao ◽

Junxian Hu ◽

Qingyi He

Keyword(s):

Western Blotting ◽

Macrophage Polarization ◽

Bone Defects ◽

The Other ◽

Formyl Peptide Receptor ◽

Cell Counting ◽

M2 Macrophage ◽

M2 Macrophages ◽

Lysosomal Activity ◽

M2 Macrophage Polarization

Abstract Background When multicystic vesicles (precursors of exosomes) are formed in cells, there are two results. One is decomposition by lysosomes, and the other is the generation of exosomes that are transported out through the transmembrane. On the other hand, M2 macrophages promote the formation of local vascularization and provide necessary support for the repair of bone defects. To provide a new idea for the treatment of bone defects, the purpose of our study was to investigate the effect of WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met-NH2) peptide on the secretion of exosomes from murine bone marrow-derived MSCs (mBMSCs) and the effect of exosomes on the polarization of M2 macrophages. Methods The WKYMVm peptide was used to activate the formyl peptide receptor 2 (FPR2) pathway in mBMSCs. First, we used Cell Counting Kit-8 (CCK-8) to detect the cytotoxic effect of WKYMVm peptide on mBMSCs. Second, we used western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) to detect the expression of interferon stimulated gene 15 (ISG15) and transcription factor EB (TFEB) in mBMSCs. Then, we detected lysosomal activity using a lysozyme activity assay kit. Third, we used an exosome extraction kit and western blotting to detect the content of exosomes secreted by mBMSCs. Fourth, we used immunofluorescence and western blotting to count the number of polarized M2 macrophages. Finally, we used an inhibitor to block miRNA-146 in exosomes secreted by mBMSCs and counted the number of polarized M2 macrophages. Results We first found that the WKYMVm peptide had no toxic effect on mBMSCs at a concentration of 1 μmol/L. Second, we found that when the FPR2 pathway was activated by the WKYMVm peptide in mBMSCs, ISG15 and TFEB expression was decreased, leading to increased secretion of exosomes. We also found that lysosomal activity was decreased when the FPR2 pathway was activated by the WKYMVm peptide in mBMSCs. Third, we demonstrated that exosomes secreted by mBMSCs promote the polarization of M2 macrophages. Moreover, all these effects can be blocked by the WRWWWW (WRW4, H-Trp-Arg-Trp-Trp-Trp-Trp-OH) peptide, an inhibitor of the FPR2 pathway. Finally, we confirmed the effect of miRNA-146 in exosomes secreted by mBMSCs on promoting the polarization of M2 macrophages. Conclusion Our findings demonstrated the potential value of the WKYMVm peptide in promoting the secretion of exosomes by mBMSCs and eventually leading to M2 macrophage polarization. We believe that our study could provide a research basis for the clinical treatment of bone defects.

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Nanofibrous Scaffold Engineering Using Electrospinning

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2007.18111 ◽

2007 ◽

Vol 7 (12) ◽

pp. 4595-4603 ◽

Cited By ~ 15

Author(s):

R. Murugan ◽

Z. M. Huang ◽

F. Yang ◽

S. Ramakrishna

Keyword(s):

Tissue Engineering ◽

Cell Attachment ◽

Dimensional Space ◽

High Surface ◽

Critical Role ◽

High Surface Area ◽

Structural Features ◽

Tissue Growth ◽

High Porosity ◽

Fibrous Scaffold

Scaffold plays a critical role in tissue engineering where it provides necessary structural support for the cells to accommodate and to guide their growth in the three dimensional space into a specific tissue. Therefore, engineering scaffolds favorable for cell/tissue growth is of great importance and a pre-requisite for scaffold-based tissue engineering. Electrospinning is a versatile method that has been recently adapted in engineering nano-fibrous scaffolds that mimic the structural features of biological extracellular matrix (ECM). It offers many advantages over conventional scaffold methodologies, for example, capable of producing ultra-fine fibers with high porosity, high spatial orientation, high aspect ratio, and high surface area, which are highly required for the initial cell attachment, tissue formation, and continued function. Considering these astonishing merits, this article emphasis on nano-fibrous scaffold engineering by electrospinning.

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Local delivery of a novel PTHrPviamesoporous bioactive glass scaffolds to improve bone regeneration in a rat posterolateral spinal fusion model

RSC Advances ◽

10.1039/c8ra00870a ◽

2018 ◽

Vol 8 (22) ◽

pp. 12484-12493 ◽

Cited By ~ 2

Author(s):

Bo Liang ◽

Jinghuan Huang ◽

Jianguang Xu ◽

Xiaolin Li ◽

Jingfeng Li

Keyword(s):

Tissue Engineering ◽

Bioactive Glass ◽

Bone Regeneration ◽

Spinal Fusion ◽

Bone Substitutes ◽

Bone Defects ◽

Local Delivery ◽

Long Bones ◽

Fusion Model ◽

Posterolateral Spinal Fusion

With the development of tissue engineering, bone defects, such as fractured long bones or cavitary lesions, may be efficiently repaired and reconstructed using bone substitutes.

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Magnetically-Targeted Nanoparticle-Guided M2 Macrophage Polarization For Fracture Healing Promotion

10.21203/rs.3.rs-779102/v1 ◽

2021 ◽

Author(s):

Wu Zhou ◽

Ze Lin ◽

Yuan Xiong ◽

Hang Xue ◽

Wen Song ◽

...

Keyword(s):

Fracture Healing ◽

Osteogenic Differentiation ◽

Silicon Nanoparticles ◽

Macrophage Polarization ◽

Osteoblastic Differentiation ◽

Fracture Site ◽

M2 Macrophage ◽

Mesoporous Silicon ◽

M2 Macrophage Polarization ◽

M2 Phenotype

Abstract Background: Macrophages are essential for fracture healing, acting mainly through remodeling of the extracellular matrix and promotion of angiogenesis. The role of macrophages in regulating osteogenic differentiation, particularly that of the M2 phenotype, is increasingly researched. Baicalein (BCL) had also been shown to have pro-fracture-healing effects.Results: In this study, we developed mesoporous silica and Fe3O4 composite-targeted nanoparticles loaded with BCL (BCL@MMSNPs-SS-CD-NW), that could be magnetically delivered to the fracture site. These induced macrophage recruitment in a targeted manner, polarizing them towards the M2 phenotype, and thereby inducing MSCs towards osteoblastic differentiation. The mesoporous silicon nanoparticles (MSNs) were prepared with surface sulfhydrylation and amination modification, and the mesoporous channels were blocked with β-cyclodextrin. The outer layer of the mesoporous silicon was added with an amantane-modified NW targeting peptide to obtain the targeted nano-system. After entering macrophages, BCL could be released from nanoparticles since the disulfide linker could be cleaved by intracellular glutathione (GSH) resulting in the removing of CD gatekeeper, which is a key element in the pro-bone-remodeling functions, such as anti-inflammation and induction of M2 macrophage polarization to facilitate osteogenic differentiation.Conclusions: This nano-system passively accumulated in the fracture site, promoting osteogenic differentiation activities, highlighting a potent therapeutic benefit with high biosafety.

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Chitosan/ biphasic calcium phosphate nanofibrous scaffolds for bone tissue engineering

Journal of Science and Technology Issue on Information and Communications Technology ◽

10.31130/jst-ud2020-113e ◽

2020 ◽

pp. 11-17

Author(s):

Truong Le Bich Tram Truong

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Calcium Phosphate ◽

Osteogenic Differentiation ◽

Late Stage ◽

Biphasic Calcium Phosphate ◽

Cell Attachment ◽

The Novel ◽

Osteogenic Cells ◽

Nanofibrous Scaffolds

In this article, chitosan/biphasic calcium phosphate (CS/BCP)nanofibers were prepared by electrospinning. From the culture of osteogenic cells, the biocompatibility of CS/BCP nanofibrous substrates was identified and increased by the photocrosslinking. The enhancement in cell attachment and proliferation was caused by the improvement in nanofibers’ mechanical properties. The biocompatibility to osteoblasts was also promoted with the content of BCP. The osteogenic differentiation in early, middle and late stage was encouraged by the addition of BCP on nanofibrous substrates. The CS/BCP nanofibers were highly specific to osteogenic cells, revealed by difficulties in the growth of non-osteogenic cells on this composite nanofibrous scaffold. The novel nanofibrous scaffolds showed great potential in the tissue engineering of bones.

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An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00992-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Tian Ding ◽

Wenyan Kang ◽

Jianhua Li ◽

Lu Yu ◽

Shaohua Ge

Keyword(s):

Tissue Engineering ◽

Growth Factors ◽

Bone Regeneration ◽

Bone Defect ◽

Bone Repair ◽

Macrophage Polarization ◽

Tissue Engineering Scaffold ◽

Bone Morphogenetic Protein 2 ◽

In Situ Tissue Engineering

Abstract Background The regeneration of periodontal bone defect remains a vital clinical challenge. To date, numerous biomaterials have been applied in this field. However, the immune response and vascularity in defect areas may be key factors that are overlooked when assessing the bone regeneration outcomes of biomaterials. Among various regenerative therapies, the up-to-date strategy of in situ tissue engineering stands out, which combined scaffold with specific growth factors that could mimic endogenous regenerative processes. Results Herein, we fabricated a core/shell fibrous scaffold releasing basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in a sequential manner and investigated its immunomodulatory and angiogenic properties during periodontal bone defect restoration. The in situ tissue engineering scaffold (iTE-scaffold) effectively promoted the angiogenesis of periodontal ligament stem cells (PDLSCs) and induced macrophage polarization into pro-healing M2 phenotype to modulate inflammation. The immunomodulatory effect of macrophages could further promote osteogenic differentiation of PDLSCs in vitro. After being implanted into the periodontal bone defect model, the iTE-scaffold presented an anti-inflammatory response, provided adequate blood supply, and eventually facilitated satisfactory periodontal bone regeneration. Conclusions Our results suggested that the iTE-scaffold exerted admirable effects on periodontal bone repair by modulating osteoimmune environment and angiogenic activity. This multifunctional scaffold holds considerable promise for periodontal regenerative medicine and offers guidance on designing functional biomaterials. Graphic Abstract

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A Review of Macrophage MicroRNAs’ Role in Human Asthma

Cells ◽

10.3390/cells8050420 ◽

2019 ◽

Vol 8 (5) ◽

pp. 420 ◽

Cited By ~ 7

Author(s):

Gavriela Feketea ◽

Corina I Bocsan ◽

Cristian Popescu ◽

Mihaela Gaman ◽

Luminita A Stanciu ◽

...

Keyword(s):

Macrophage Polarization ◽

Critical Role ◽

Human Macrophage ◽

Published Data ◽

M2 Macrophage ◽

Macrophage Phenotype ◽

Activated Macrophages ◽

Novel Therapy ◽

Alternatively Activated Macrophages ◽

Classically Activated Macrophages

There is an imbalance in asthma between classically activated macrophages (M1 cells) and alternatively activated macrophages (M2 cells) in favor of the latter. MicroRNAs (miRNAs) play a critical role in regulating macrophage proliferation and differentiation and control the balance of M1 and M2 macrophage polarization, thereby controlling immune responses. Here we review the current published data concerning miRNAs with known correlation to a specific human macrophage phenotype and polarization, and their association with adult asthma. MiRNA-targeted therapy is still in the initial stages, but clinical trials are under recruitment or currently running for some miRNAs in other diseases. Regulating miRNA expression via their upregulation or downregulation could show potential as a novel therapy for improving treatment efficacy in asthma.

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Fabrication of 3D plotted scaffold with microporous strands for bone tissue engineering

Journal of Materials Chemistry B ◽

10.1039/c9tb02360g ◽

2020 ◽

Vol 8 (5) ◽

pp. 951-960 ◽

Cited By ~ 2

Author(s):

Ji Min Seok ◽

Thanavel Rajangam ◽

Jae Eun Jeong ◽

Sinyoung Cheong ◽

Sang Min Joo ◽

...

Keyword(s):

Tissue Engineering ◽

Bone Formation ◽

Bone Tissue Engineering ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Tissue Regeneration ◽

Cell Attachment ◽

New Bone Formation

Scaffold porosity has played a key role in bone tissue engineering aimed at effective tissue regeneration, by promoting cell attachment, proliferation, and osteogenic differentiation for new bone formation.

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