Tailoring Materials for Modulation of Macrophage Fate

Li, Jinhua; Jiang, Xinquan; Li, Hongjun; Gelinsky, Michael; Gu, Zhen

doi:10.1002/adma.202004172

Cited by 182 publications

(163 citation statements)

References 409 publications

(438 reference statements)

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“…[ 6,7 ] These prior studies suggest that materials designed to carry physical screens with their gaps to bioactive material surface are tunable and can both modulate and elucidate delicate cell–ECM interactions. [ 8–13 ]…”

Section: Introductionmentioning

confidence: 99%

Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation

et al. 2021

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In native microenvironment, diverse physical barriers exist to dynamically modulate stem cell recruitment and differentiation for tissue repair. In this study, nanoassembly‐based magnetic screens of various sizes are utilized, and they are elastically tethered over an RGD ligand (cell‐adhesive motif)‐presenting material surface to generate various nanogaps between the screens and the RGDs without modulating the RGD density. Large screens exhibiting low RGD distribution stimulate integrin clustering to facilitate focal adhesion, mechanotransduction, and differentiation of stem cells, which are not observed with small screens. Magnetic downward pulling of the large screens decreases the nanogaps, which dynamically suppress the focal adhesion, mechanotransduction, and differentiation of stem cells. Conversely, magnetic upward pulling of the small screens increases the nanogaps, which dynamically activates focal adhesion, mechanotransduction, and differentiation of stem cells. This regulation mechanism is also shown to be effective in the microenvironment in vivo. Further diversifying the geometries of the physical screens can further enable diverse modalities of multifaceted and safe unscreening of the distributed RGDs to unravel and modulate stem cell differentiation for tissue repair.

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Section: Introductionmentioning

confidence: 99%

Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation

et al. 2021

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“…M1 macrophages play important roles in in ammation by secreting pro-in ammatory mediators, including IL-1, IL-6, TNF-α, and IL-12. In contrast, M2 macrophages are characterised by the secretion of high levels of anti-in ammatory mediators, such as IL-10 and TGF-β [25][26][27]. In the present study, we found that macrophages, which partly govern tissue regeneration, showed different polarization patterns after translation of MSCs from different sources.…”

Section: Discussionmentioning

confidence: 50%

Dental Pulp Mesenchymal Stem Cells Promote Polarization of M2 Macrophages and Accelerate Wound Healing by Secreting CCL2

Yang

et al. 2021

Preprint

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Background Mesenchymal stem cells (MSCs) are widely used in tissue engineering owing to their regenerative potential and immunomodulatory capacity. The crosstalk between MSCs and the host immune function plays a key role in the efficiency of tissue regeneration. However, the difference in immunological modulation and tissue regeneration function between MSCs from different sources remains unclear. Methods Human mesenchymal stem cells derived from bone marrow (BMMSCs), periodontal ligament (PDLSCs), adipose (ADSCs), and dental pulp (DPSCs) were obtained and induced to form cell sheets under the condition of 20 ug/ml vitamin C. The MSC cell sheets carried by hydroxyapatite/tricalciumphosphate (HA/TCP) particles were transplanted subcutaneously into C57BL6 mice for 8 weeks. Histological analyses were performed to detect the tissue regeneration potential and macrophages polarization in vivo. Then, THP-1 macrophages were co-cultured with MSCs and quantitative real-time polymerase chain reaction, immunofluorescent staining, western blotting, and enzyme-linked immunosorbent assay were used to investigate the function and mechanism of MSCs on macrophages in vitro. Finally, a wound healing model of the palatal mucosa was performed to confirm the effect of MSCs on macrophages and tissue healing efficiency. Results Compared to PDLSCs, BMMSCs, and ADSCs, DPSCs exhibited greater tissue regeneration potential, with greater tissue volume, higher Ki67 expression, and less apoptosis in the regenerated tissue of wild-type C57BL6 mice. In addition, DSPCs triggered more M2 macrophages in the regenerated tissue than other MSCs. Our data showed that DPSCs exhibited higher expression levels of C-C Motif Chemokine Ligand 2 (CCL2), and specific blocking of CCL2 by neutralising antibodies can significantly inhibit the DPSCs-induced polarization of M2 macrophages. Finally, DPSCs transplantation promoted wound healing of the palatal mucosa and M2 macrophages polarization in vivo, which could be significantly impaired by CCL2 neutralising antibody. Conclusions Our data indicate that DPSCs exert better tissue regeneration potential and immunoregulatory function by secreting CCL2. These results suggest that CCL2 application can enhance MSC-mediated tissue regeneration or wound healing.

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“…It is well established that M2 macrophages help to inhibit inflammation and promote tissue regeneration, whereas M1 macrophages have the opposite effects. [ 16 ] Therefore, the cell composition in the defect areas was analyzed to explore the possible explanation for the chirality‐dependent variation in inflammation and regeneration. At day 3, the number of macrophages with the M2 surface marker CD206 was higher in the M group than in the P group, whereas the proportion of macrophages with the M1 surface marker CCR7 in both groups was similar (Figure 2d and Figure S2, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Chirality Bias Tissue Homeostasis by Manipulating Immunological Response

et al. 2021

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The physiological chirality of extracellular environments is substantially affected by pathological diseases. However, how this stereochemical variation drives host immunity remains poorly understood. Here, it is reported that pathology‐mimetic M‐nanofibrils—but not physiology‐mimetic P‐nanofibrils—act as a defense mechanism that helps to restore tissue homeostasis by manipulating immunological response. Quantitative multi‐omics in vivo and in vitro shows that M‐nanofibrils significantly inhibit inflammation and promote tissue regeneration by upregulating M2 macrophage polarization and downstream immune signaling compared with P‐nanofibrils. Molecular analysis and theoretical simulation demonstrate that M‐chirality displays higher stereo‐affinity to cellular binding, which induces higher cellular contractile stress and activates mechanosensitive ion channel PIEZOl to conduct Ca2+ influx. In turn, the nuclear transfer of STAT is biased by Ca2+ influx to promote M2 polarization. These findings underscore the structural mechanisms of disease, providing design basis for immunotherapy with bionic functional materials.

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Tailoring Materials for Modulation of Macrophage Fate

Cited by 182 publications

References 409 publications

Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation

Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation

Dental Pulp Mesenchymal Stem Cells Promote Polarization of M2 Macrophages and Accelerate Wound Healing by Secreting CCL2

Chirality Bias Tissue Homeostasis by Manipulating Immunological Response

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