Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
ACS Appl Mater Interfaces. 2024 Oct 23;16(42):56730-56743. doi: 10.1021/acsami.4c11890. Epub 2024 Oct 12.
Electrical stimulation has been used clinically as an adjunct therapy to accelerate the healing of bone defects, and its mechanism requires further investigations. The complexity of the physiological microenvironment makes it challenging to study the effect of electrical signal on cells alone. Therefore, an artificial system mimicking cell microenvironment was developed to address this issue. In this work, a novel electrical stimulation system was constructed based on polypyrrole nanowires (ppyNWs) with a high aspect ratio. Synthesized ppyNWs formed a conductive network in the composited hydrogel which contained modified gelatin with methacrylate, providing a conductive cell culture matrix for bone marrow mesenchymal stem cells. The dual-network conductive hydrogel had improved mechanical, electrical, and hydrophilic properties. It was able to imitate the three-dimensional structure of the cell microenvironment and allowed adjustable electrical stimulations in the following system. This hydrogel was integrated with cell culture plates, platinum electrodes, copper wires, and external power sources to construct the artificial electrical stimulation system. The optimum voltage of the electrical stimulation system was determined to be 2 V, which exhibited remarkable biocompatibility. Moreover, this system had significant promotion in cell spreading, osteogenic makers, and bone-related gene expression of stem cells. RNA-seq analysis revealed that osteogenesis was correlated to Notch, BMP/Smad, and calcium signal pathways. It was proven that this biomimetic system could regulate the osteogenesis procedure, and it provided further information about how the electrical signal regulates osteogenic differentiations.
电刺激已被临床用作辅助治疗方法，以加速骨缺损的愈合，其机制需要进一步研究。生理微环境的复杂性使得单独研究电信号对细胞的影响变得具有挑战性。因此，开发了一种人工系统来模拟细胞微环境，以解决这个问题。在这项工作中，构建了一种基于具有高纵横比的聚吡咯纳米线（ppyNWs）的新型电刺激系统。合成的 ppyNWs 在含有甲基丙烯酰化改性明胶的复合水凝胶中形成了一个导电网络，为骨髓间充质干细胞提供了一个导电的细胞培养基质。双网络导电水凝胶具有改善的机械、电气和亲水性能。它能够模拟细胞微环境的三维结构，并允许在以下系统中进行可调的电刺激。该水凝胶与细胞培养板、铂电极、铜线和外部电源集成在一起，构建了人工电刺激系统。确定了电刺激系统的最佳电压为 2V，其表现出显著的生物相容性。此外，该系统在干细胞的细胞扩展、成骨标志物和与骨相关的基因表达方面具有显著的促进作用。RNA-seq 分析表明，成骨作用与 Notch、BMP/Smad 和钙信号通路相关。事实证明，这种仿生系统可以调节成骨过程，并提供了更多关于电信号如何调节成骨分化的信息。
