Multifunctional Conductive and Electrogenic Hydrogel Repaired Spinal Cord Injury via Immunoregulation and Enhancement of Neuronal Differentiation

Author:

Liu Mingshan1,Zhang Wencan1,Han Shuwei1,Zhang Dapeng1,Zhou Xiaolong1,Guo Xianzheng1,Chen Haosheng1,Wang Haifeng2,Jin Lin3ORCID,Feng Shiqing14,Wei Zhijian1

Affiliation:

1. Department of Orthopaedics Qilu Hospital of Shandong University Shandong University Centre for Orthopaedics Advanced Medical Research Institute Shandong University No. 107 Wenhua West Road, Lixia District Jinan 250012 China

2. Department of Orthopaedics The Second Hospital of Shandong University No. 247 Beiyuan Street, Tianqiao District Jinan 250033 China

3. International Joint Research Laboratory for Biomedical Nanomaterials of Henan Zhoukou Normal University No. 6, Middle Section of Wenchang Avenue, Chuanhui District Zhoukou 466001 China

4. Department of Orthopedics Tianjin Medical University General Hospital International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord Injury No. 154 Anshan Road, Heping District Tianjin 300052 China

Abstract

AbstractSpinal cord injury (SCI) is a refractory neurological disorder. Due to the complex pathological processes, especially the secondary inflammatory cascade and the lack of intrinsic regenerative capacity, it is difficult to recover neurological function after SCI. Meanwhile, simulating the conductive microenvironment of the spinal cord reconstructs electrical neural signal transmission interrupted by SCI and facilitates neural repair. Therefore, a double‐crosslinked conductive hydrogel (BP@Hydrogel) containing black phosphorus nanoplates (BP) is synthesized. When placed in a rotating magnetic field (RMF), the BP@Hydrogel can generate stable electrical signals and exhibit electrogenic characteristic. In vitro, the BP@Hydrogel shows satisfactory biocompatibility and can alleviate the activation of microglia. When placed in the RMF, it enhances the anti‐inflammatory effects. Meanwhile, wireless electrical stimulation promotes the differentiation of neural stem cells (NSCs) into neurons, which is associated with the activation of the PI3K/AKT pathway. In vivo, the BP@Hydrogel is injectable and can elicit behavioral and electrophysiological recovery in complete transected SCI mice by alleviating the inflammation and facilitating endogenous NSCs to form functional neurons and synapses under the RMF. The present research develops a multifunctional conductive and electrogenic hydrogel for SCI repair by targeting multiple mechanisms including immunoregulation and enhancement of neuronal differentiation.

Funder

National Key Research and Development Program of China Stem Cell and Translational Research

Publisher

Wiley

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