A shear-thinning, ROS-scavenging hydrogel combined with dental pulp stem cells promotes spinal cord repair by inhibiting ferroptosis

Yibo Ying; Zhiyang Huang; Yurong Tu; Qiuji Wu; Zhaoyu Li; Yifan Zhang; Huilei Yu; Annian Zeng; Hanzhi Huang; Jiahui Ye; Weiyang Ying; Min Chen; Zhiyi Feng; Ziyue Xiang; Qingsong Ye; Sipin Zhu; Zhouguang Wang

doi:10.1016/j.bioactmat.2022.09.019

A shear-thinning, ROS-scavenging hydrogel combined with dental pulp stem cells promotes spinal cord repair by inhibiting ferroptosis

Bioact Mater. 2022 Oct 11:22:274-290. doi: 10.1016/j.bioactmat.2022.09.019. eCollection 2023 Apr.

Authors

Yibo Ying^{1

2}, Zhiyang Huang^{1

2}, Yurong Tu^{1

2}, Qiuji Wu^{1

2}, Zhaoyu Li³, Yifan Zhang^{1

2}, Huilei Yu^{1

2}, Annian Zeng^{1

2}, Hanzhi Huang^{1

2}, Jiahui Ye^{1

2}, Weiyang Ying^{1

2

4}, Min Chen^{1

2}, Zhiyi Feng^{1

2}, Ziyue Xiang^{1

2}, Qingsong Ye^{5

6}, Sipin Zhu^{1

2}, Zhouguang Wang^{1

2}

Affiliations

¹ School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
² Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
³ Department of Overseas Education College, Jimei University, Xiamen, Fujian, China.
⁴ Department of Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
⁵ Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan, 460030, Hubei, China.
⁶ Massachusetts General Hospital, Harvard University, Boston, 02114, USA.

Abstract

Spinal cord injury (SCI) is a serious clinical disease. Due to the deformability and fragility of the spinal cord, overly rigid hydrogels cannot be used to treat SCI. Hence, we used TPA and Laponite to develop a hydrogel with shear-thinning ability. This hydrogel exhibits good deformation, allowing it to match the physical properties of the spinal cord; additionally, this hydrogel scavenges ROS well, allowing it to inhibit the lipid peroxidation caused by ferroptosis. According to the in vivo studies, the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism. In addition, dental pulp stem cells (DPSCs) were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses. It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.

Keywords: Dental pulp stem cells; Ferroptosis; ROS-Scavenging; Shear-thinning hydrogel; Synaptic regulation.