Polyhydroxyphenylvalerate/polycaprolactone nanofibers improve the life-span and mechanoresponse of human IPSC-derived cortical neuronal cells

Abstract

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.

Keywords: Cortical neurons; Electrospinning; HiPSC; Mechanoresponse; Neuroregeneration; Polyhydroxyalkanoates.