Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration

Hao Zhou; Jinpeng He; Renfeng Liu; Jun Cheng; Yuhao Yuan; Wanpu Mao; Jun Zhou; Honghui He; Qianqi Liu; Wei Tan; Cijun Shuai; Youwen Deng

doi:10.1016/j.bioactmat.2024.02.036

Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration

Bioact Mater. 2024 Mar 15:37:51-71. doi: 10.1016/j.bioactmat.2024.02.036. eCollection 2024 Jul.

Authors

Hao Zhou^{1

2}, Jinpeng He¹, Renfeng Liu¹, Jun Cheng¹, Yuhao Yuan³, Wanpu Mao², Jun Zhou⁴, Honghui He², Qianqi Liu¹, Wei Tan¹, Cijun Shuai⁵, Youwen Deng¹

Affiliations

¹ Department of Spine Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
² Department of Joint Surgery and Sports Medicine, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421002, China.
³ Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁴ Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁵ State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha, 410083, China.

Abstract

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1β)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.

Keywords: IL-17/ERK signaling pathway; Intervertebral disc degeneration; Metal-phenolic network; Pyroptosis; Reactive oxygen species.