An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling.
An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling.
复制标题
可注射水凝胶通过促进细胞外基质重塑增强脊髓损伤后的组织修复。
DOI：
10.1038/s41467-017-00583-8
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发表时间：
2017-09-14
影响因子：
16.6
通讯作者：
Kim BG
中科院分区：
文献类型：
--
作者：
Hong LTA;Kim YM;Park HH;Hwang DH;Cui Y;Lee EM;Yahn S;Lee JK;Song SC;Kim BG
脑或脊髓损伤后形成的囊腔是中枢神经系统(CNS)组织修复的主要障碍。在这里，我们报告了注射咪唑-聚(有机磷腈)(I-5)，一种具有温度敏感的溶胶-凝胶转变行为的水凝胶，几乎完全消除了临床相关的大鼠脊髓损伤模型中的囊腔。囊腔由富含纤维连接蛋白的细胞外基质连接。纤维化细胞外基质重塑是由纤维化细胞外基质内巨噬细胞表达的基质金属蛋白酶-9介导的。一种缺少咪唑部分的聚(有机磷腈)水凝胶，它通过组胺受体与巨噬细胞物理上相互作用，表现出显著减弱的桥联作用。注射I-5改善了协调运动，这种功能恢复伴随着有髓白质和运动神经元的保护以及腰椎运动神经元轴突神经支配的增加。我们的研究表明，炎症细胞和可注射生物材料之间的动态相互作用可以诱导有益的细胞外基质重塑，从而刺激中枢神经系统损伤后的组织修复。脑或脊髓损伤后形成的囊腔是一个主要障碍。在这里，作者展示了注射咪唑聚(有机磷腈)，一种具有温度敏感的溶胶-凝胶转变行为的水凝胶，几乎完全消除了临床相关的大鼠脊髓损伤模型中的囊腔。
The cystic cavity that develops following injuries to brain or spinal cord is a major obstacle for tissue repair in central nervous system (CNS). Here we report that injection of imidazole-poly(organophosphazenes) (I-5), a hydrogel with thermosensitive sol–gel transition behavior, almost completely eliminates cystic cavities in a clinically relevant rat spinal cord injury model. Cystic cavities are bridged by fibronectin-rich extracellular matrix. The fibrotic extracellular matrix remodeling is mediated by matrix metalloproteinase-9 expressed in macrophages within the fibrotic extracellular matrix. A poly(organophosphazenes) hydrogel lacking the imidazole moiety, which physically interacts with macrophages via histamine receptors, exhibits substantially diminished bridging effects. I-5 injection improves coordinated locomotion, and this functional recovery is accompanied by preservation of myelinated white matter and motor neurons and an increase in axonal reinnervation of the lumbar motor neurons. Our study demonstrates that dynamic interactions between inflammatory cells and injectable biomaterials can induce beneficial extracellular matrix remodeling to stimulate tissue repair following CNS injuries. The cystic cavity that develops following injuries to brain or spinal cord is a major obstacle. Here the authors show an injection of imidazole poly(organophosphazenes), a hydrogel with thermosensitive sol–gel transition behavior, almost completely eliminates cystic cavities in a clinically relevant rat spinal cord injury model.
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影响因子：
6.7
作者：
Czerner, Christoph P.;Klos, Andreas;Neumann, Detlef
通讯作者：
Neumann, Detlef
影响因子：
14
作者：
Iwasaki, Motoyuki;Wilcox, Jared T.;Fehlings, Michael G.
通讯作者：
Fehlings, Michael G.
影响因子：
17.1
作者：
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通讯作者：
Song, Soo-Chang
影响因子：
4.2
作者：
Hamers, FPT;Koopmans, GC;Joosten, EAJ
通讯作者：
Joosten, EAJ
影响因子：
3.7
作者：
Cigognini D;Satta A;Colleoni B;Silva D;Donegà M;Antonini S;Gelain F
通讯作者：
Gelain F