Synergistic Modulating of Mitochondrial Transfer and Immune Microenvironment to Attenuate Discogenic Pain

Abstract Discogenic pain, caused by intervertebral disc degeneration (IVDD), is a prevalent and challenging condition to treat effectively. Macrophage infiltration with neural ectopic in‐growth resulting from structural disturbances within the intervertebral disc (IVD) is a major cause of discogenic...

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Main Authors: Xinzhou Wang, Zhenyu Guo, Linjie Chen, Jing Sun, Kenny Yat Hong Kwan, Morgan Jones, Yan Michael Li, Yangyang Hu, Xueqiang Wang, Pooyan Makvandi, Xiangyang Wang, Qiuping Qian, Yunlong Zhou, Aimin Wu
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202500128
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Summary:Abstract Discogenic pain, caused by intervertebral disc degeneration (IVDD), is a prevalent and challenging condition to treat effectively. Macrophage infiltration with neural ectopic in‐growth resulting from structural disturbances within the intervertebral disc (IVD) is a major cause of discogenic pain. This work systematically reveals how nanoparticles can synergistically regulate the immune microenvironment and mitochondrial communication to attenuate discogenic pain. The antioxidant metal‐polyphenol nanoparticle system can sequentially regulate macrophage phenotype and mitochondrial delivery efficiency. This strategy circumvents the necessity for mitochondrial isolation and preservation techniques that are typically required in conventional mitochondrial transplantation procedures. Furthermore, it facilitates the effective and sustained delivery of mitochondria to damaged cells. In vivo, this nanoparticle formulation effectively preserves the IVD height, maintains the structural integrity of the nucleus pulposus (NP), and restores pain thresholds. Thus, this nanoplatform offers an effective approach to traditional surgical treatments for discogenic pain, with significant potential for clinical application.
ISSN:2198-3844