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A DAMP-Scavenging, IL-10-Releasing Hydrogel Promotes Neural Regeneration and Motor Function Recovery after Spinal Cord Injury
He Shen, Bai Xu, Chao Yang, Weiwei Xue, Zhifeng You, Xianming Wu, Dezun Ma, Dan Shao, Kam Leong, Jianwu Dai
Biomaterials
Abstract
Spinal cord injury (SCI) creates an inflammatory microenvironment characterized by damage-associated molecular patterns (DAMPs) and immune cell activation that exacerbate secondary damage and impair neurological recovery. Here we develop an immunoregulatory hydrogel scaffold for treating SCI that scavenges DAMPs and slowly releases the anti-inflammatory cytokine interleukin-10 (IL-10). We created this dual-functional scaffold by modifying a photocrosslinked gelatin hydrogel with the cationic, DAMP-binding polymer poly (amidoamine) and with IL-10, and compared the therapeutic activity of this scaffold with that of gelatin-only, gelatin + poly (amidoamine), and gelatin + IL-10 scaffolds in vitro and in vivo. In vitro, the dual-functional scaffold scavenged anionic DAMPs and exhibited sustained release of IL-10, reduced the proinflammatory responses of macrophages and microglia, and enhanced the neurogenic differentiation of neural stem cells. In a complete transection SCI mouse model, the injected dual-functional scaffold suppressed proinflammatory cytokine production, promoted the M2 macrophage/microglia phenotype, and led to neural regeneration and axon growth without scar formation to a greater extent than the single-function or control scaffolds. This DAMP-scavenging, IL-10-releasing scaffold provides a new strategy for promoting neural regeneration and motor function recovery following severe SCI.
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论文编号: |
DOI:10.1016/j.biomaterials.2021.121279 |
论文题目: |
A DAMP-Scavenging, IL-10-Releasing Hydrogel Promotes Neural Regeneration and Motor Function Recovery after Spinal Cord Injury |
英文论文题目: |
A DAMP-Scavenging, IL-10-Releasing Hydrogel Promotes Neural Regeneration and Motor Function Recovery after Spinal Cord Injury |
第一作者: |
He Shen, Bai Xu, Chao Yang, Weiwei Xue, Zhifeng You, Xianming Wu, Dezun Ma, Dan Shao, Kam Leong, Jianwu Dai |
英文第一作者: |
He Shen, Bai Xu, Chao Yang, Weiwei Xue, Zhifeng You, Xianming Wu, Dezun Ma, Dan Shao, Kam Leong, Jianwu Dai |
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2021-12-09 |
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摘要: |
Spinal cord injury (SCI) creates an inflammatory microenvironment characterized by damage-associated molecular patterns (DAMPs) and immune cell activation that exacerbate secondary damage and impair neurological recovery. Here we develop an immunoregulatory hydrogel scaffold for treating SCI that scavenges DAMPs and slowly releases the anti-inflammatory cytokine interleukin-10 (IL-10). We created this dual-functional scaffold by modifying a photocrosslinked gelatin hydrogel with the cationic, DAMP-binding polymer poly (amidoamine) and with IL-10, and compared the therapeutic activity of this scaffold with that of gelatin-only, gelatin + poly (amidoamine), and gelatin + IL-10 scaffolds in vitro and in vivo. In vitro, the dual-functional scaffold scavenged anionic DAMPs and exhibited sustained release of IL-10, reduced the proinflammatory responses of macrophages and microglia, and enhanced the neurogenic differentiation of neural stem cells. In a complete transection SCI mouse model, the injected dual-functional scaffold suppressed proinflammatory cytokine production, promoted the M2 macrophage/microglia phenotype, and led to neural regeneration and axon growth without scar formation to a greater extent than the single-function or control scaffolds. This DAMP-scavenging, IL-10-releasing scaffold provides a new strategy for promoting neural regeneration and motor function recovery following severe SCI. |
英文摘要: |
Spinal cord injury (SCI) creates an inflammatory microenvironment characterized by damage-associated molecular patterns (DAMPs) and immune cell activation that exacerbate secondary damage and impair neurological recovery. Here we develop an immunoregulatory hydrogel scaffold for treating SCI that scavenges DAMPs and slowly releases the anti-inflammatory cytokine interleukin-10 (IL-10). We created this dual-functional scaffold by modifying a photocrosslinked gelatin hydrogel with the cationic, DAMP-binding polymer poly (amidoamine) and with IL-10, and compared the therapeutic activity of this scaffold with that of gelatin-only, gelatin + poly (amidoamine), and gelatin + IL-10 scaffolds in vitro and in vivo. In vitro, the dual-functional scaffold scavenged anionic DAMPs and exhibited sustained release of IL-10, reduced the proinflammatory responses of macrophages and microglia, and enhanced the neurogenic differentiation of neural stem cells. In a complete transection SCI mouse model, the injected dual-functional scaffold suppressed proinflammatory cytokine production, promoted the M2 macrophage/microglia phenotype, and led to neural regeneration and axon growth without scar formation to a greater extent than the single-function or control scaffolds. This DAMP-scavenging, IL-10-releasing scaffold provides a new strategy for promoting neural regeneration and motor function recovery following severe SCI. |
刊物名称: |
Biomaterials |
英文刊物名称: |
Biomaterials |
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其它备注: |
He Shen, Bai Xu, Chao Yang, Weiwei Xue, Zhifeng You, Xianming Wu, Dezun Ma, Dan Shao, Kam Leong, Jianwu Dai. A DAMP-Scavenging, IL-10-Releasing Hydrogel Promotes Neural Regeneration and Motor Function Recovery after Spinal Cord Injury. Biomaterials. DOI:10.1016/j.biomaterials.2021.121279 |
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