Remodeling Microenvironment for Endogenous Repair through Precise Modulation of Chondroitin Sulfate Proteoglycans Following Spinal Cord Injury
Xiumin Sun
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorHaiqian 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
Search for more papers by this authorZan Tan
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorYuhui Hou
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorMao Pang
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorShengfeng Chen
Joint International Research Laboratory of CNS Regeneration Ministry of Education, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510623 China
Search for more papers by this authorLongyou Xiao
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorQiuju Yuan
Centre of Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, 999077 China
Search for more papers by this authorBin Liu
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorCorresponding Author
Limin Rong
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding 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]
Search for more papers by this authorXiumin Sun
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorHaiqian 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
Search for more papers by this authorZan Tan
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorYuhui Hou
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorMao Pang
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorShengfeng Chen
Joint International Research Laboratory of CNS Regeneration Ministry of Education, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510623 China
Search for more papers by this authorLongyou Xiao
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorQiuju Yuan
Centre of Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, 999077 China
Search for more papers by this authorBin Liu
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
Search for more papers by this authorCorresponding Author
Limin Rong
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding 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]
Search for more papers by this authorAbstract
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.
Open Research
Data Availability Statement
Research data are not shared.
Supporting Information
Filename | Description |
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smll202205012-sup-0001-SuppMat.pdf513.1 KB | Supporting Information |
smll202205012-sup-0002-VideoS1.mov30.6 MB | Supplemental Video 1 |
smll202205012-sup-0003-VideoS2.mov25 MB | Supplemental Video 2 |
smll202205012-sup-0004-VideoS3.mov33.2 MB | Supplemental Video 3 |
smll202205012-sup-0005-VideoS4.mov28.9 MB | Supplemental Video 4 |
smll202205012-sup-0006-VideoS5.mov38.2 MB | Supplemental Video 5 |
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