The Biomimetic Electrical\nStimulation System Inducing\nOsteogenic Differentiations of BMSCs

Electrical stimulation has been used clinically as an\nadjunct therapy\nto accelerate the healing of bone defects, and its mechanism requires\nfurther investigations. The complexity of the physiological microenvironment\nmakes it challenging to study the effect of electrical signal on cells\nalone. Therefore, an artificial system mimicking cell microenvironment <i>in vitro</i> was developed to address this issue. In this work,\na novel electrical stimulation system was constructed based on polypyrrole\nnanowires (ppyNWs) with a high aspect ratio. Synthesized ppyNWs formed\na conductive network in the composited hydrogel which contained modified\ngelatin with methacrylate, providing a conductive cell culture matrix\nfor bone marrow mesenchymal stem cells. The dual-network conductive\nhydrogel had improved mechanical, electrical, and hydrophilic properties.\nIt was able to imitate the three-dimensional structure of the cell\nmicroenvironment and allowed adjustable electrical stimulations in\nthe following system. This hydrogel was integrated with cell culture\nplates, platinum electrodes, copper wires, and external power sources\nto construct the artificial electrical stimulation system. The optimum\nvoltage of the electrical stimulation system was determined to be\n2 V, which exhibited remarkable biocompatibility. Moreover, this system\nhad significant promotion in cell spreading, osteogenic makers, and\nbone-related gene expression of stem cells. RNA-seq analysis revealed\nthat osteogenesis was correlated to Notch, BMP/Smad, and calcium signal\npathways. It was proven that this biomimetic system could regulate\nthe osteogenesis procedure, and it provided further information about\nhow the electrical signal regulates osteogenic differentiations.