Volume 19, Issue 6 2205012
Research Article

Remodeling Microenvironment for Endogenous Repair through Precise Modulation of Chondroitin Sulfate Proteoglycans Following Spinal Cord Injury

Xiumin Sun

Xiumin Sun

Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China

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Haiqian Liu

Haiqian Liu

Joint International Research Laboratory of CNS Regeneration Ministry of Education, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510623 China

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515 China

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Zan Tan

Zan Tan

Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China

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Yuhui Hou

Yuhui Hou

Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China

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Mao Pang

Mao Pang

Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China

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Shengfeng Chen

Shengfeng Chen

Joint International Research Laboratory of CNS Regeneration Ministry of Education, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510623 China

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Longyou Xiao

Longyou Xiao

Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China

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Qiuju Yuan

Qiuju Yuan

Centre of Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, 999077 China

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Bin Liu

Bin Liu

Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China

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Limin Rong

Corresponding Author

Limin Rong

Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China

E-mail: [email protected]; [email protected]

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Liumin He

Corresponding Author

Liumin He

Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China

Joint International Research Laboratory of CNS Regeneration Ministry of Education, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510623 China

E-mail: [email protected]; [email protected]

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First published: 18 November 2022
Citations: 4

Abstract

The fluid-filled cystic cavity sealed by a dense scar developed following traumatic spinal cord injury (SCI) has been a major obstacle to neural regeneration and functional recovery. Here the transected lesion is bridged using a functional self-assembling peptide (F-SAP) hydrogel loaded with membrane-permeable intracellular sigma peptide (ISP) and intracellular LAR peptide (ILP), targeted at perturbing chondroitin sulfate proteoglycan (CSPG) inhibitory signaling. As compared to F-SAP hydrogel loaded with chondroitinase ABC, the F-SAP+ISP/ILP promotes a beneficial anti-inflammatory response via manipulation of microglia/macrophages infiltration and assembly of extracellular matrix (ECM) molecules into fibrotic matrix rather than scarring tissues. The remodeled ECM creates a permissive environment that supports axon regrowth and the formation of synaptic connections with neurons derived from endogenous neural stem cells. The remodeled networks contribute to functional recovery, as demonstrated by improved hind limb movements and electrophysiological properties. This work proposes a unique mechanism that ECM remodeling induced by CSPG-manipulation-based anti-inflammation can construct a permissive environment for neural regeneration, and shed light on the advancement of manipulation of cascading cellular and molecular events potential for endogenous repair of SCI.

Conflict of Interest

The authors declare no conflict of interest.

Data Availability Statement

Research data are not shared.

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