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Polyhydroxyphenylvalerate/polycaprolactone nanofibers improve the life-span and mechanoresponse of human IPSC-derived cortical neuronal cells
Biomaterials Advances ( IF 5.5 ) Pub Date : 2020-03-12 , DOI: 10.1016/j.msec.2020.110832
Federico Cerrone , Tatyana Pozner , Aarif Siddiqui , Paolo Ceppi , Beate Winner , Murugan Rajendiran , Ramesh Babu , Hossam S. Ibrahim , Brian J. Rodriguez , Jürgen Winkler , Keith J. Murphy , Kevin E. O'Connor

The physico-chemical characteristics of the extracellular matrix (ECM) cause mechanical cues that could elicit responses in the survival rate of cortical neuronal cells. Efficient neurite outgrowth in vitro, is critical for successful cultivation of cortical neuronal cells and the potential for attempts at regeneration of the central nervous system (CNS) in vivo. Relatively soft and hydrophilic, microbially synthesized aromatic polyester, polyhydroxyphenylvalerate (PHPV) was blended 50:50 with the stiff and hydrophobic polycaprolactone (PCL) and electrospun in microfibers for use in a 3D (CellCrown™) configuration and in a 2D coverslip coated configuration. This blend allows a 2.3-fold increase in the life-span of human induced pluripotent stem derived cortical neuronal cells (hiPS) compared to pure PCL fibers. HiPS-derived cortical neuronal cells grown on PHPV/PCL fibers show a 3.8-fold higher cumulative neurite elaboration compared to neurites grown on PCL fibers only. 96% of cortical neuronal cells die after 8 days of growth when plated on PCL fibers alone while >83% and 55% are alive on PHPV/PCL fibers on day 8 and day 17, respectively. An increased migration rate of cortical neuronal cells is also promoted by the blend compared to the PCL fibers alone. The critical survival rate improvement of hiPS derived cortical neuronal cells on PHPV/PCL blend holds promise in using these biocompatible nanofibers as implantable materials for regenerative purposes of an active cortical neuronal population after full maturation in vitro.



中文翻译:

聚羟基戊酸/聚己内酯纳米纤维可改善IPSC衍生的皮层神经元细胞的寿命和机械响应

细胞外基质(ECM)的物理化学特征会引起机械提示,从而可能引发皮质神经元细胞存活率的响应。高效神经突增生的体外,对皮质神经元细胞的培育成功,并在中枢神经系统(CNS)的再生为尝试的潜在关键体内。将相对柔软和亲水的微生物合成的芳族聚酯,聚羟基戊酸戊酸酯(PHPV)与刚性和疏水性聚己内酯(PCL)混合50:50,并在微纤维中静电纺丝,用于3D(CellCrown™)配置和2D盖玻片涂层配置。与纯PCL纤维相比,这种共混物可使人诱导的多能干来源的皮质神经元细胞(hiPS)的寿命延长2.3倍。与仅在PCL纤维上生长的神经突相比,在PHPV / PCL纤维上生长的HiPS衍生的皮质神经元细胞显示出更高的累积神经突精细化3.8倍。仅在PCL纤维上铺板时,有96%的皮质神经元细胞在生长8天后死亡,而分别在第8天和第17天,> 83%和55%的PHPV / PCL纤维存活。与单独的PCL纤维相比,该混合物还促进了皮质神经元细胞的迁移速率增加。在PHPV / PCL混合物上,hiPS衍生的皮质神经元细胞的关键存活率的提高在将这些生物相容性纳米纤维用作可植入材料用于完全成熟后活性皮质神经元群体的再生目的方面具有希望体外

更新日期:2020-03-12
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