Biomaterials
Abstract
Spinal cord injury (SCI) creates an inflammatorymicroenvironmentcharacterized by damage-associatedmolecular patterns(DAMPs) and immunecell activationthat 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 scaffoldsin vitroandin vivo.In vitro, the dual-functional scaffold scavenged anionic DAMPs and exhibitedsustained releaseof IL-10, reduced the proinflammatory responses of macrophages andmicroglia, and enhanced the neurogenic differentiation ofneural stem cells. In a complete transection SCI mouse model, the injected dual-functional scaffold suppressedproinflammatory cytokineproduction, promoted the M2 macrophage/microgliaphenotype, and led toneural regenerationandaxon growthwithout 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.
| 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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| 发表年度: | 2021-12-09 |
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| 摘要: | Spinal cord injury (SCI) creates an inflammatorymicroenvironmentcharacterized by damage-associatedmolecular patterns(DAMPs) and immunecell activationthat 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 scaffoldsin vitroandin vivo.In vitro, the dual-functional scaffold scavenged anionic DAMPs and exhibitedsustained releaseof IL-10, reduced the proinflammatory responses of macrophages andmicroglia, and enhanced the neurogenic differentiation ofneural stem cells. In a complete transection SCI mouse model, the injected dual-functional scaffold suppressedproinflammatory cytokineproduction, promoted the M2 macrophage/microgliaphenotype, and led toneural regenerationandaxon growthwithout 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 inflammatorymicroenvironmentcharacterized by damage-associatedmolecular patterns(DAMPs) and immunecell activationthat 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 scaffoldsin vitroandin vivo.In vitro, the dual-functional scaffold scavenged anionic DAMPs and exhibitedsustained releaseof IL-10, reduced the proinflammatory responses of macrophages andmicroglia, and enhanced the neurogenic differentiation ofneural stem cells. In a complete transection SCI mouse model, the injected dual-functional scaffold suppressedproinflammatory cytokineproduction, promoted the M2 macrophage/microgliaphenotype, and led toneural regenerationandaxon growthwithout 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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