A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair

Biao Yang; Chengzhen Liang; Di Chen; Feng Cheng; Yuang Zhang; Shaoke Wang; Jiawei Shu; Xianpeng Huang; Jingkai Wang; Kaishun Xia; Liwei Ying; Kesi Shi; Chenggui Wang; Xuhua Wang; Fangcai Li; Qian Zhao; Qixin Chen

doi:10.1016/j.bioactmat.2021.11.032

A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair

Bioact Mater. 2021 Dec 23:15:103-119. doi: 10.1016/j.bioactmat.2021.11.032. eCollection 2022 Sep.

Authors

Biao Yang^{1

2

3}, Chengzhen Liang^{1

2

3}, Di Chen⁴, Feng Cheng^{1

2

3}, Yuang Zhang^{1

2

3}, Shaoke Wang^{1

2

3}, Jiawei Shu^{1

2

3}, Xianpeng Huang^{1

2

3}, Jingkai Wang^{1

2

3}, Kaishun Xia^{1

2

3}, Liwei Ying^{1

2

3}, Kesi Shi^{1

2

3}, Chenggui Wang^{1

2

3}, Xuhua Wang^{1

5}, Fangcai Li^{1

2

3}, Qian Zhao⁶, Qixin Chen^{1

2

3}

Affiliations

¹ Department of Orthopedics Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
² Orthopedics Research Institute of Zhejiang University, Hangzhou, 310009, Zhejiang, China.
³ Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang, China.
⁴ Ningbo Research Institute of Zhejiang University, Ningbo, 315100, Zhejiang, China.
⁵ NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.
⁶ State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang, China.

Abstract

The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the physically crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca²⁺ signaling cascades. Overall, this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.

Keywords: Biomimetic scaffolds; Conducting polymer; Nerve regeneration; Spinal cord injury; Supramolecular hydrogels.