M2 macrophages-derived exosomes combined with acellular cartilage matrix scaffolds promote osteochondral regeneration via modulatory microenvironment

Yin, Han; Yan, Zineng; Wu, Jiarui; Li, Muzhe; Ge, Qian; Zhang, Tieyuan; Ma, Yang; Xiang, Sheng; Liu, Shuyun; Guo, Quanyi

doi:10.1016/j.matdes.2023.111672

Cited by 9 publications

(4 citation statements)

References 46 publications

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“…This subtype is capable of exerting both pro-inflammatory and anti-inflammatory effects, which might explain the observed elevation in TNFα levels. Therefore, these findings indicated that BEVs might not only induce the transition of M0 macrophages to an anti-inflammatory M2 phenotype, consistent with previous studies [20], but also may be involved in the regulation of M2 macrophage subtypes.…”

Section: Discussionsupporting

confidence: 91%

Osteo-immunomodulatory effects of macrophage-derived extracellular vesicles treated with biphasic calcium phosphate ceramics on bone regeneration

Chen,

Liu,

Liu

et al. 2024

Biomed. Mater.

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Literature on osteoimmunology has demonstrated that macrophages have a great influence on biomaterial-induced bone formation. However, there are almost no reports clarifying the osteo-immunomodulatory capacity of macrophage-derived extracellular vesicles (EVs). This study comprehensively investigated the effects of EVs derived from macrophages treated with biphasic calcium phosphate (BCP) ceramics (BEVs) on vital events associated with BCP-induced bone formation such as immune response, angiogenesis, and osteogenesis. It was found that compared with EVs derived from macrophages alone (control, CEVs), BEVs preferentially promoted macrophage polarization towards a wound-healing M2 phenotype, enhanced migration, angiogenic differentiation, and tube formation of human umbilical vein endothelial cells (HUVECs), and induced osteogenic differentiation of mesenchymal stem cells (MSCs). Analysis of 15 differentially expressed microRNAs (DEMs) related to immune, angiogenesis, and osteogenesis suggested that BEVs exhibited good immunomodulatory, pro-angiogenic, and pro-osteogenic abilities, which might be attributed to their specific miRNA cargos. These findings not only deepen our understanding of biomaterial-mediated osteoinduction, but also suggest that EVs derived from biomaterial-treated macrophages hold great promise as therapeutic agents with desired immunomodulatory capacity for bone regeneration.

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Section: Discussionsupporting

confidence: 91%

Osteo-immunomodulatory effects of macrophage-derived extracellular vesicles treated with biphasic calcium phosphate ceramics on bone regeneration

Chen,

Liu,

Liu

et al. 2024

Biomed. Mater.

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“…Chondrocyte implantation is believed to modulate the immune response by inhibiting inflammation, modulating immune cell function, increasing immune tolerance, and reducing autoimmune responses [108,109]. Chondrocytes can also regulate the innate immune system through interactions with myeloid dendritic cells, natural killer cells, macrophages, and other cells [110,111]. Studies showed better therapeutic effects in OA applications.…”

Section: Cell Therapymentioning

confidence: 99%

Enhanced Surface Immunomodification of Engineered Hydrogel Materials through Chondrocyte Modulation for the Treatment of Osteoarthritis

Yao,

Huo,

et al. 2024

Coatings

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Osteoarthritis (OA) is characterized by cartilage degeneration and synovial inflammation, with chondrocytes playing a pivotal role in this disease. However, inflammatory mediators, mechanical stress, and oxidative stress can compromise functionality. The occurrence and progression of OA are intrinsically linked to the immune response. Current research on the treatment of OA mainly concentrates on the synergistic application of drugs and tissue engineering. The surface of engineered hydrogel materials can be immunomodified to affect the function of chondrocytes in drug therapy, gene therapy, and cell therapy. Prior studies have concentrated on the drug-loading function of hydrogels but overlooked the immunomodulatory role of chondrocytes. These modifications can inhibit the proliferation and differentiation of chondrocytes, reduce the inflammatory response, and promote cartilage regeneration. The surface immunomodification of engineered hydrogel materials can significantly enhance their efficacy in the treatment of OA. Thus, immunomodulatory tissue engineering has significant potential for treating osteoarthritis.

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“…[19] In addition, the EVs from M2 polarized macrophages exhibit more antiinflammatory properties that are beneficial for tissue repair. [20,21] Hence, the macrophages derived Migs, particularly from the M2 polarized macrophages, may also be suitable for tissue regeneration. After culturing RAW264.7 cells on different surfaces, there seemed to be more Migs formation alongside the retraction fibers on NTs surface as revealed by scanning electron microscope (SEM) examination (Figure 1B).…”

Section: The Nts Surface Can Induce Macrophages M2 Polarization and M...mentioning

confidence: 99%

“…The mechanism for Migs-induced osteogenesis in vivo may relate to diverse aspects, encompassing the release of growth factors, immunomodulation, matrix synthesis regulation, intercellular communication, as well as antioxidant and anti-apoptotic effects. [20,35] In addition, a large number of studies have shown that Migs are closely related to lots of normal cell physiology and diseases. It can serve as mediators for intercellular communication to coordinate the morphogenesis of organs, [5] participate in rebuilding injured muscles, [36] change the tumor microenvironment, [37] and be the sensitive indicator for early podocyte stress and damage.…”

Section: M2 Macrophages Derived Migs Decoration Can Promote Implant S...mentioning

confidence: 99%

The M2 Macrophages Derived Migrasomes From the Surface of Titania Nanotubes Array as a New Concept for Enhancing Osteogenesis

Li,

Zhao,

Wang

et al. 2024

Adv Healthcare Materials

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As a newly discovered substrate anchored extracellular vesicles, migrasomes (Migs) may bring a new opportunity for manipulating target cells bioactivities. In this study, the M2 macrophages derived Migs were obtained by titania nanotubes surface (NTs). Due to the benefits of nanostructured, the NTs surface was not only able to induce RAW264.7 for M2 polarization, but also generated more Migs formation, which could be internalized by following seeded mesenchymal stem cells (MSCs). Then the NTs surface induced Migs were collected by density‐gradient centrifugation for MSCs treatment. As indicated by immunofluorescence staining, alkaline phosphatase activity and alizarin red staining, the osteogenic differentiation capacity of MSCs was significantly enhanced by Migs treatment, in line with the dosage. By RNA‐sequence analysis, the enhancement of osteogenic differentiation was correlated with PI3K‐AKT pathway activation that might be originated from the M2 polarization state of donor cells. Finally, the Migs were coated onto Ti surface for therapeutic application. Both the in vitro and in vivo analysis revealed that the Migs coated Ti implant showed significant enhancement of osteogenesis. In conclusion, this study suggests that the nanosurface may be a favorable platform for Migs production, which may bring a new concept for tissue regeneration.This article is protected by copyright. All rights reserved

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M2 macrophages-derived exosomes combined with acellular cartilage matrix scaffolds promote osteochondral regeneration via modulatory microenvironment

Cited by 9 publications

References 46 publications

Osteo-immunomodulatory effects of macrophage-derived extracellular vesicles treated with biphasic calcium phosphate ceramics on bone regeneration

Osteo-immunomodulatory effects of macrophage-derived extracellular vesicles treated with biphasic calcium phosphate ceramics on bone regeneration

Enhanced Surface Immunomodification of Engineered Hydrogel Materials through Chondrocyte Modulation for the Treatment of Osteoarthritis

The M2 Macrophages Derived Migrasomes From the Surface of Titania Nanotubes Array as a New Concept for Enhancing Osteogenesis

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