Macrophage polarization plays roles in bone formation instructed by calcium phosphate ceramics

Li, Mingzheng; Guo, Xiaodong; Qi, Wei; Wu, Zhenzhen; Bruijn, Joost D. de; Xiao, Yu; Bao, Chongyun; Yuan, Huipin

doi:10.1039/c9tb02932j

Cited by 54 publications

(37 citation statements)

References 85 publications

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“…The different groups of mammary gland tissues were collected and homogenized with PBS on ice, and then the supernatants were collected by centrifugation. The levels of the five inflammatory cytokines were determined by ELISA kits (Multisciences, Hangzhou, China) according to the manufacturer's instructions [53,55].…”

Section: Elisa Assay Of Cytokine Expression Levelsmentioning

confidence: 99%

Anti-Staphylococcus aureus Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo

Zhang

et al. 2021

Vaccines

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Staphylococcus aureus is a causative agent of bovine mastitis, capable of causing significant economic losses to the dairy industry worldwide. This study focuses on obtaining single-chain fragment variables (scFvs) against the virulence factors of S. aureus and evaluates the protective effect of scFvs on bovine mammary epithelial (MAC-T) cells and mice mammary gland tissues infected by S. aureus. After five rounds of bio-panning, four scFvs targeting four virulence factors of S. aureus were obtained. The complementarity-determining regions (CDRs) of these scFvs exhibited significant diversities, especially CDR3 of the VH domain. In vitro, each of scFvs was capable of inhibiting S. aureus growth and reducing the damage of MAC-T cells infected by S. aureus. Preincubation of MAC-T cells with scFvs could significantly attenuate the effect of apoptosis and necrosis compared with the negative control group. In vivo, the qPCR and ELISA results demonstrated that scFvs reduced the transcription and expression of Tumor Necrosis Factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, and IL-18. Histopathology and myeloperoxidase (MPO) results showed that scFvs ameliorated the histopathological damages and reduced the inflammatory cells infiltration. The overall results demonstrated the positive anti-inflammatory effect of scFvs, revealing the potential role of scFvs in the prevention and treatment of S. aureus infections.

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Section: Elisa Assay Of Cytokine Expression Levelsmentioning

confidence: 99%

Anti-Staphylococcus aureus Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo

Zhang

et al. 2021

Vaccines

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“…Similarly, Zn 2+ deficiency aggravated inflammation, reduced the numbers of M2-polarized M s and increased the numbers of M1-polarized M s [ 31 , 32 ]. In addition, β-TCP was also reported to possess the ability to shift M polarization toward the M2 subtype [ 33 – 35 ]. M2-polarized M s guide MSC differentiation along the osteogenic pathway and subsequently increase bone mineralization [ 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Sustained zinc release in cooperation with CaP scaffold promoted bone regeneration via directing stem cell fate and triggering a pro-healing immune stimuli

Huang

Zhu

et al. 2021

J Nanobiotechnol

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Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into β-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M$$\varphi $$ φ s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

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“…Recently, among the different phases of wound healing, several studies have shown that the correct development and understanding of the inflammatory phase, and more precisely of macrophage response, is crucial to achieve a successful tissue regeneration 2 , 3 . Interestingly, different biomaterial properties such as chemical signals, topography or stiffness have shown to modify the macrophage response in cartilage 4 , bone 5 and hernia 6 . Depending on the environmental cues, recruited macrophages can differentiate in different phenotypes, which have been classified in several subsets.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the immunomodulatory effects of cobalt, copper and magnesium ions in a pro inflammatory environment

Díez-Tercero

Delgado

Bosch-Rué

et al. 2021

Sci Rep

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Biomaterials and scaffolds for Tissue Engineering are widely used for an effective healing and regeneration. However, the implantation of these scaffolds causes an innate immune response in which the macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype is crucial to avoid chronic inflammation. Recent studies have showed that the use of bioactive ions such as cobalt (Co2+), copper (Cu2+) and magnesium (Mg2+) could improve tissue regeneration, although there is limited evidence on their effect on the macrophage response. Therefore, we investigated the immunomodulatory potential of Co2+, Cu2+ and Mg2+ in macrophage polarization. Our results indicate that Mg2+ and concentrations of Cu2+ lower than 10 μM promoted the expression of M2 related genes. However, higher concentrations of Cu2+ and Co2+ (100 μM) stimulated pro-inflammatory marker expression, indicating a concentration dependent effect of these ions. Furthermore, Mg2+ were able to decrease M1 marker expression in presence of a mild pro-inflammatory stimulus, showing that Mg2+ can be used to modulate the inflammatory response, even though their application can be limited in a strong pro-inflammatory environment.

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Macrophage polarization plays roles in bone formation instructed by calcium phosphate ceramics

Abstract: TCPs recruited more macrophages which polarized towards tissue repair macrophages to create a favourable osteo-immune environment for material-instructed bone formation.

Cited by 54 publications

References 85 publications

Anti-Staphylococcus aureus Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo

Anti-Staphylococcus aureus Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo

Sustained zinc release in cooperation with CaP scaffold promoted bone regeneration via directing stem cell fate and triggering a pro-healing immune stimuli

Evaluation of the immunomodulatory effects of cobalt, copper and magnesium ions in a pro inflammatory environment

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