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具有可编程形状记忆特性和促进神经分化活性的可注射丝胶蛋白支架用于严重缺血性中风的个体化脑修复

Injectable silk sericin scaffolds with programmable shape-memory property and neuro-differentiation-promoting activity for individualized brain repair of severe ischemic stroke.

作者信息

Wang Jian, Li Xiaolin, Song Yu, Su Qiangfei, Xiaohalati Xiakeerzhati, Yang Wen, Xu Luming, Cai Bo, Wang Guobin, Wang Zheng, Wang Lin

机构信息

Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

Bioact Mater. 2020 Dec 29;6(7):1988-1999. doi: 10.1016/j.bioactmat.2020.12.017. eCollection 2021 Jul.

Abstract

Severe ischemic stroke damages neuronal tissue, forming irregular-shaped stroke cavities devoid of supporting structure. Implanting biomaterials to provide structural and functional support is thought to favor ingrowth of regenerated neuronal networks. Injectable hydrogels capable of gelation are often utilized for stroke repair, but challenged by incomplete gelation and imprecise control over end-macrostructure. Injectable shape-memory scaffolds might overcome these limitations, but are not explored for stroke repair. Here, we report an injectable, photoluminescent, carbon-nanotubes-doped sericin scaffold (CNTs-SS) with programmable shape-memory property. By adjusting CNTs' concentrations, CNTs-SS' recovery dynamics can be mathematically calculated at the scale of seconds, and its shapes can be pre-designed to precisely match any irregular-shaped cavities. Using a preclinical stroke model, we show that CNTs-SS with the customized shape is successfully injected into the cavity and recovers its pre-designed shape to well fit the cavity. Notably, CNTs-SS' near-infrared photoluminescence enables non-invasive, real-time tracking after implantation. Moreover, as a cell carrier, CNTs-SS not only deliver bone marrow mesenchymal stem cells (BMSCs) into brain tissues, but also functionally promote their neuronal differentiation. Together, we for the first time demonstrate the feasibility of applying injectable shape-memory scaffolds for stroke repair, paving the way for personalized stroke repair.

摘要

严重缺血性中风会损害神经元组织,形成没有支撑结构的不规则形状的中风腔。植入生物材料以提供结构和功能支持被认为有利于再生神经网络的向内生长。能够凝胶化的可注射水凝胶常用于中风修复,但存在凝胶化不完全和对最终宏观结构控制不精确的挑战。可注射形状记忆支架可能会克服这些限制,但尚未用于中风修复的研究。在此,我们报告了一种具有可编程形状记忆特性的可注射、光致发光、碳纳米管掺杂的丝胶支架(CNTs-SS)。通过调整碳纳米管的浓度,可以在秒级尺度上通过数学计算得出CNTs-SS的恢复动力学,并且其形状可以预先设计以精确匹配任何不规则形状的腔体。使用临床前中风模型,我们表明定制形状的CNTs-SS成功注入腔体内并恢复其预先设计的形状以很好地贴合腔体。值得注意的是,CNTs-SS的近红外光致发光能够在植入后进行非侵入性实时跟踪。此外,作为细胞载体,CNTs-SS不仅能将骨髓间充质干细胞(BMSCs)输送到脑组织中,还能在功能上促进其向神经元分化。我们首次共同证明了应用可注射形状记忆支架进行中风修复的可行性,为个性化中风修复铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fabf/7786039/fee0042b4cbd/fx1.jpg

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