Construction of Biofunctionalized Anisotropic Hydrogel Micropatterns and Their Effect on Schwann Cell Behavior in Peripheral Nerve Regeneration
Construction of Biofunctionalized Anisotropic Hydrogel Micropatterns and Their Effect on Schwann Cell Behavior in Peripheral Nerve Regeneration
复制标题
生物功能化各向异性水凝胶微图案的构建及其对周围神经再生中雪旺细胞行为的影响
DOI：
10.1021/acsami.9b08510
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发表时间：
2019-10-16
影响因子：
9.5
通讯作者：
Yang, Yumin
中科院分区：
文献类型：
--
作者：
Li, Guicai;Li, Shenjie;Yang, Yumin
水凝胶由于其优异的物理化学和生物相容性在组织再生中具有广阔的应用前景，而各向异性微图案已被证明可以定向诱导细胞排列和加速细胞迁移。然而，生物功能化各向异性水凝胶微图对神经再生的影响鲜有报道。本研究首先通过原位自由基聚合和微成型制备了具有排列脊/槽结构的各向异性聚丙烯酰胺（PAM）水凝胶微模式，然后利用YIGSR肽进行生物功能化，以更好地促进细胞生长。对制备的水凝胶的形态、溶胀率、润湿性、力学性能和稳定性进行了表征。利用FTIR、免疫荧光染色和ELISA检测YIGSR肽在PAM水凝胶上的成功固定情况。观察其对雪旺细胞粘附、定向生长和生物学功能的影响。结果表明，具有内孔结构的各向异性PAM水凝胶微图具有良好的稳定性、溶胀性和力学性能。YIGSR肽可以很好地固定在水凝胶微图上，固定率为62.6%。生物功能化的各向异性水凝胶微图可有效调节雪旺细胞的定向生长，与单一水凝胶微图相比，可明显上调BDNF（40%）和β -actin（50%）的表达，而不会对雪旺细胞正常分泌神经营养因子产生负面影响。据我们所知，这是第一次研究生物功能化各向异性水凝胶微图案的构建及其对神经再生的影响，这可能为神经再生应用人工植入物的设计和开发提供实验和理论依据。
Hydrogels have promising application in tissue regeneration due to their excellent physicochemical and biocompatible properties, whereas anisotropic micropatterns are been proven to directionally induce cell alignment and accelerate cell migration. However, an effect of biofunctionalized anisotropic hydrogel micropatterns on nerve regeneration has rarely been reported. In this study, the anisotropic polyacrylamide (PAM) hydrogel micropatterns with aligned ridge/ groove structures were first prepared via in situ free radical polymerization and micromolding, and then biofunctionalized using YIGSR peptide for better promoting cell growth. The morphology, swelling ratio, wettability, mechanical properties, and stability of the prepared hydrogel were characterized. The successful immobilization of YIGSR peptide on the PAM hydrogel was monitored using FTIR, immunofluorescence staining, and ELISA. The effects on adhesion, directional growth, and biological function of Schwann cells were evaluated. The results displayed that the anisotropic PAM hydrogel micropatterns with inner porous structure possessed good stability, swelling, and mechanical properties. The YIGSR peptide could be well immobilized on hydrogel micropatterns with a percentage of 62.6%. The biofunctionalized anisotropic hydrogel micropatterns could effectively regulate the orientation growth of Schwann cells, and obviously up-regulate BDNF (40%) and beta-actin (50%) expression compared with single hydrogel micropatterns, without negatively affecting the normal secretion of neurotropic factors by Schwann cells. To the best of our knowledge, this is the first time to study the construction and effect of biofunctionalized anisotropic hydrogel micropatterns on nerve regeneration, which may provide an experimental and theoretical basis for the design and development of artificial implants for nerve regeneration application.