Synthetic 3D PEG-Anisogel Tailored with Fibronectin Fragments Induce Aligned Nerve Extension
Synthetic 3D PEG-Anisogel Tailored with Fibronectin Fragments Induce Aligned Nerve Extension
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DOI：
10.1021/acs.biomac.9b00891
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发表时间：
2019-11-01
影响因子：
6.2
通讯作者：
De Laporte，Laura
中科院分区：
文献类型：
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作者：
Licht，Christopher;Rose，Jonas C.;De Laporte，Laura
一种以酶交联聚乙二醇（PEG）为基础的水凝胶被设计成以三维方式促进和排列神经细胞。为了使可注射的、生物惰性的聚乙二醇基材料支持细胞生长，对其机械和生化性能进行了优化。在凝胶过程中，重组纤维连接蛋白片段（FNIII9*-10/12-14）偶联到PEG主链上，在附近提供细胞粘附和生长因子结合域。与全长纤维连接蛋白相比，FNIII9*-10/12-14在相同浓度下支持神经生长。在3D环境中，只有储存模量为~ 10 Pa的超软1 w/v% PEG水凝胶才能促进神经元的生长。通过添加磁性排列的微元素（如棒状微凝胶或短纤维），该凝胶被用来建立第一个完全合成的、可注射的各向异性凝胶。Anisogel导致线性神经突延伸，并代表了临床转化方向的一大步，有机会治疗急性脊髓损伤。
An enzymatically cross-linked polyethylene glycol (PEG)-based hydrogel was engineered to promote and align nerve cells in a three-dimensional manner. To render the injectable, otherwise bioinert, PEG-based material supportive for cell growth, its mechanical and biochemical properties were optimized. A recombinant fibronectin fragment (FNIII9*-10/12-14) was coupled to the PEG backbone during gelation to provide cell adhesive and growth factor binding domains in close vicinity. Compared to full-length fibronectin, FNIII9*-10/12-14 supports nerve growth at similar concentrations. In a 3D environment, only the ultrasoft 1 w/v% PEG hydrogels with a storage modulus of ∼10 Pa promoted neuronal growth. This gel was used to establish the first fully synthetic, injectable Anisogel by the addition of magnetically aligned microelements, such as rod-shaped microgels or short fibers. The Anisogel led to linear neurite extension and represents a large step in the direction of clinical translation with the opportunity to treat acute spinal cord injuries.