Unsaturated polyurethane films grafted with enantiomeric polylysine promotes macrophage polarization to a M2 phenotype through PI3K/Akt1/mTOR axis

Duan, Yuanyuan; Zheng, Honghao; Li, Zehua; Yao, Yingming; Ding, Jie; Wang, Xuemei; Nakkala, Jayachandra Reddy; Zhang, Deteng; Wang, Zhaoyi; Zuo, Xingang; Zheng, Xiaowen; Ling, Jun; Gao, Changyou

doi:10.1016/j.biomaterials.2020.120012

Cited by 70 publications

(63 citation statements)

References 53 publications

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“…Several studies have demonstrated a crucial role for the Akt/mTOR pathway in the M1 and M2 polarization of macrophages [ 32 – 34 ]. However, there have been no studies on the function of the Akt/mTOR pathway in H. pylori -induced macrophage polarization.…”

Section: Resultsmentioning

confidence: 99%

The Degree of Helicobacter pylori Infection Affects the State of Macrophage Polarization through Crosstalk between ROS and HIF-1α

Rong

Lai

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background and Objective. Helicobacter pylori (H. pylori) is involved in macrophage polarization, but the specific mechanism is not well understood. Therefore, this study is aimed at investigating the effects of the degree of H. pylori infection on the macrophage polarization state and the crosstalk between reactive oxygen species (ROS) and hypoxia-inducible factor 1 α (HIF-1α) in this process. Methods. The expression of CD86, CD206, and HIF-1α in the gastric mucosa was evaluated through immunohistochemistry. RAW 264.7 cells were cocultured with H. pylori at various multiplicities of infection (MOIs), and iNOS, CD86, Arg-1, CD206, and HIF-1α expression was detected by Western blot, PCR, and ELISA analyses. ROS expression was detected with the fluorescent probe DCFH-DA. Macrophages were also treated with the ROS inhibitor NAC or HIF-1α inhibitor YC-1. Results. Immunohistochemical staining revealed that the macrophage polarization state was associated with the progression of gastric lesions and state of H. pylori infection. The MOI of H. pylori affected macrophage polarization, and H. pylori enhanced the expression of ROS and HIF-1α in macrophages. A low MOI of H. pylori promoted both the M1 and M2 phenotypes, while a high MOI suppressed the M2 phenotype. Furthermore, ROS inhibition attenuated HIF-1α expression and switched macrophage polarization from M1 to M2. However, HIF-1α inhibition suppressed ROS expression and inhibited both the M1 phenotype and the M2 phenotype. Inhibition of ROS or HIF-1α also suppressed the activation of the Akt/mTOR pathway, which was implicated in H. pylori-induced macrophage polarization. Conclusions. Macrophage polarization is associated with the progression of gastric lesions and state of H. pylori infection. The MOI of H. pylori influences the macrophage polarization state. Crosstalk between ROS and HIF-1α regulates H. pylori-induced macrophage polarization via the Akt/mTOR pathway.

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Section: Resultsmentioning

confidence: 99%

The Degree of Helicobacter pylori Infection Affects the State of Macrophage Polarization through Crosstalk between ROS and HIF-1α

Rong

Lai

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Besides adopting ECM ingredients to produce biomimetic surfaces, other natural polymers were also used to construct immunoregulatory interfaces. In a recent study, enantiomeric polylysine was grafted on the surface of poly(propylene fumarate) polyurethane films (PPFU) to investigate the polarisation-regulatory effects on macrophages [ 181 ]. According to the expression analysis of paracrine cytokines and polarisation related genes, the poly-d-lysine grafted PPFU film exhibited a more effective induction of in vivo M2 polarisation and a thinner fibrous capsule wrapping implants.…”

Section: Harnessing the Power Of Macrophages For Enhanced Osteogenesimentioning

confidence: 99%

Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches

Niu

Wang

Shi

et al. 2021

Bioactive Materials

132

123

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A coordinated interaction between osteogenesis and osteoimmune microenvironment is essential for successful bone healing. In particular, macrophages play a central regulatory role in all stages of bone repair. Depending on the signals they sense, these highly plastic cells can mediate the host immune response against the exterior signals of molecular stimuli and implanted scaffolds, to exert regenerative potency to a varying extent. In this article, we first encapsulate the immunomodulatory functions of macrophages during bone regeneration into three aspects, as sweeper, mediator and instructor. We introduce the phagocytic role of macrophages in different bone healing periods (‘sweeper’) and overview a variety of paracrine cytokines released by macrophages either mediating cell mobilisation, vascularisation and matrix remodelling (‘mediator’), or directly driving the osteogenic differentiation of bone progenitors and bone repair (‘instructor’). Then, we systematically classify and discuss the emerging engineering strategies to recruit, activate and modulate the phenotype transition of macrophages, to exploit the power of endogenous macrophages to enhance the performance of engineered bone tissue.

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“…[42] Despite the fact that PLL is known to be immunogenic and evokes inflammatory responses, recent results show that PLL influence macrophages toward the M2 polarization. [43][44][45] On the other hand, CHT is a biodegradable polysaccharide derived from chitin which possesses an inherent antimicrobial activity. [46] Its immunomodulatory properties are poorly understood, however some studies have shown that CHT is a powerful activator of macrophage's inflammasomes, while others demonstrated CHT's modulatory capacity to polarize macrophages into a M2 anti-inflammatory phenotype.…”

Section: Discussionmentioning

confidence: 99%

An Immunomodulatory Miniaturized 3D Screening Platform Using Liquefied Capsules

Nadine

Correia

Mano

2021

Adv Healthcare Materials

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A critical determinant of successful clinical outcomes is the host's response to the biomaterial. Therefore, the prediction of the immunomodulatory bioperformance of biomedical devices following implantation is of utmost importance. Herein, liquefied capsules are proposed as immunomodulatory miniaturized 3D platforms for the high-content combinatorial screening of different polymers that could be used generically in scaffolds. Additionally, the confined and liquefied core of capsules affords a cell-mediated 3D assembly with bioinstructive microplatforms, allowing to study the potential synergistic effect that cells in tissue engineering therapies have on the immunological environment before implantation. As a proof-of-concept, three different polyelectrolytes, ranging in charge density and source, are used. Poly(L-lysine)-, alginate-, and chitosan-ending capsules with or without encapsulated mesenchymal stem/stromal cells (MSCs) are placed on top of a 2D culture of macrophages. Results show that chitosan-ending capsules, as well as the presence of MSCs, favor the balance of macrophage polarization toward a more regenerative profile, through the up-regulation of anti-inflammatory markers, and the release of pro-regenerative cytokines. Overall, the developed system enables the study of the immunomodulatory bioperformance of several polymers in a cost-effective and scalable fashion, while the paracrine signaling between encapsulated cells and the immunological environment can be simultaneously evaluated.

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Unsaturated polyurethane films grafted with enantiomeric polylysine promotes macrophage polarization to a M2 phenotype through PI3K/Akt1/mTOR axis

Cited by 70 publications

References 53 publications

The Degree of Helicobacter pylori Infection Affects the State of Macrophage Polarization through Crosstalk between ROS and HIF-1α

The Degree of Helicobacter pylori Infection Affects the State of Macrophage Polarization through Crosstalk between ROS and HIF-1α

Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches

An Immunomodulatory Miniaturized 3D Screening Platform Using Liquefied Capsules

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