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Review
. 2022 Apr 29:9:813169.
doi: 10.3389/fbioe.2021.813169. eCollection 2021.

Strategies for Biomaterial-Based Spinal Cord Injury Repair via the TLR4-NF-κB Signaling Pathway

Bin Lv  1 , Naiting Shen  2 , Zhangrong Cheng  1 , Yuhang Chen  1 , Hua Ding  3 , Jishan Yuan  3 , Kangchen Zhao  1 , Yukun Zhang  1
Affiliations
Review

Strategies for Biomaterial-Based Spinal Cord Injury Repair via the TLR4-NF-κB Signaling Pathway

Bin Lv et al. Front Bioeng Biotechnol. .

Abstract

The repair and motor functional recovery after spinal cord injury (SCI) has remained a clinical challenge. Injury-induced gliosis and inflammation lead to a physical barrier and an extremely inhibitory microenvironment, which in turn hinders the recovery of SCI. TLR4-NF-κB is a classic implant-related innate immunomodulation signaling pathway and part of numerous biomaterial-based treatment strategies for SCI. Numerous experimental studies have demonstrated that the regulation of TLR4-NF-κB signaling pathway plays an important role in the alleviation of inflammatory responses, the modulation of autophagy, apoptosis and ferroptosis, and the enhancement of anti-oxidative effect post-SCI. An increasing number of novel biomaterials have been fabricated as scaffolds and carriers, loaded with phytochemicals and drugs, to inhibit the progression of SCI through regulation of TLR4-NF-κB. This review summarizes the empirical strategies for the recovery after SCI through individual or composite biomaterials that mediate the TLR4-NF-κB signaling pathway.

Keywords: TLR4-NF-κB; autophagy; biomaterial; signaling pathway; spinal cord injury.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The role of TLR4-NF-κB signaling pathway in modulating inflammation, autophagy and apoptosis. TLR4 activates transcription factor NF-κB through MyD88-dependent/TRIF-dependent signaling pathways respectively, thus up-regulating the expression of inflammatory mediators and chemokines, and exacerbating neuroinflammation. However, the TLR4-NF-κB signaling pathway can be inhibited by certain kinds of miRNAs. In addition, NF-κB imparts reciprocal regulation with TNF-α. Activated NF-κB regulates TNF-α homeostasis, and TNF-α in turn activates NF-κB via TRADD/TRAF2/MAPK signaling pathway and promotes apoptosis through TRADD/FADD/caspase8 pathway. On the other hand, the TLR4/MAPK-P38 pathway plays an important role in the regulation of inflammation and autophagy, eliciting innate immune responses.
FIGURE 2
FIGURE 2
Hydrogel as a stent repair strategy for spinal cord injury.
FIGURE 3
FIGURE 3
Schematic diagram of curcumin encapsulated in hydrogel for central nervous system injury.
See this image and copyright information in PMC

References

    1. Abbas W. A., Ibrahim M. E., El-Naggar M., Abass W. A., Abdullah I. H., Awad B. I., et al. (2020). Recent Advances in the Regenerative Approaches for Traumatic Spinal Cord Injury: Materials Perspective. ACS Biomater. Sci. Eng. 6, 6490–6509. 10.1021/acsbiomaterials.0c01074 - DOI - PubMed
    1. Abbaszadeh F., Fakhri S., Khan H. (2020). Targeting Apoptosis and Autophagy Following Spinal Cord Injury: Therapeutic Approaches to Polyphenols and Candidate Phytochemicals. Pharmacol. Res. 160, 105069. 10.1016/j.phrs.2020.105069 - DOI - PubMed
    1. Adil M. M., Vazin T., Ananthanarayanan B., Rodrigues G. M. C., Rao A. T., Kulkarni R. U., et al. (2017). Engineered Hydrogels Increase the post-transplantation Survival of Encapsulated hESC-Derived Midbrain Dopaminergic Neurons. Biomaterials 136, 1–11. 10.1016/j.biomaterials.2017.05.008 - DOI - PubMed
    1. Akira S., Takeda K. (2004). Toll-like Receptor Signalling. Nat. Rev. Immunol. 4, 499–511. 10.1038/nri1391 - DOI - PubMed
    1. Akira S., Uematsu S., Takeuchi O. (2006). Pathogen Recognition and Innate Immunity. Cell 124, 783–801. 10.1016/j.cell.2006.02.015 - DOI - PubMed

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