中枢神经系统(CNS)疾病对人类健康的威胁越来越大,强调迫切需要探索各种中枢神经系统疾病的发病机制和治疗方法。初级神经元直接从动物或人类获得,具有广泛的应用,包括疾病建模,机制探索和药物开发。然而,传统的二维(2D)单一培养不能类似于中枢神经系统的天然微环境。随着人们对中枢神经系统复杂性的日益认识和新型生物材料的显著发展,体外模型经历了巨大的创新,从2D单培养到三维(3D)多细胞培养。这篇综述的范围包括近年来各种原代神经元体外模型的进展,以提供初级神经元模型的模式和应用的整体视图,以及它们如何与生物制造技术的革命联系起来。已特别注意初级神经元与生物材料之间的相互作用。首先,简要介绍了中枢神经系统建模和原代神经元培养的历史。接下来,从2D培养,离体模型,球体,基于支架的模型,3D生物打印模型,和微流控芯片。Modalities,应用程序,优势,和上述模型的局限性分别进行了描述。最后,我们探索了未来的前景,为基础科学研究方法如何推进我们对中枢神经系统的理解提供新的见解,并强调了未来几十年原代神经元培养的一些未来方向。
Central nervous system (CNS) diseases have been a growing threat to the health of humanity, emphasizing the urgent need of exploring the pathogenesis and therapeutic approaches of various CNS diseases. Primary neurons are directly obtained from animals or humans, which have wide applications including disease modeling, mechanism exploration and drug development. However, traditional two-dimensional (2D) monoculture cannot resemble the native microenvironment of CNS. With the increasing understanding of the complexity of the CNS and the remarkable development of novel biomaterials, in vitro models have experienced great innovation from 2D monoculture toward three-dimensional (3D) multicellular culture. The scope of this review includes the progress of various in vitro models of primary neurons in recent years to provide a holistic view of the modalities and applications of primary neuron models and how they have been connected with the revolution of biofabrication techniques. Special attention has been paid to the interaction between primary neurons and biomaterials. First, a brief introduction on the history of CNS modeling and primary neuron culture was conducted. Next, detailed progress in novel in vitro models were discussed ranging from 2D culture, ex vivo model, spheroid, scaffold-based model, 3D bioprinting model, and microfluidic chip. Modalities, applications, advantages, and limitations of the aforementioned models were described separately. Finally, we explored future prospects, providing new insights into how basic science research methodologies have advanced our understanding of the CNS, and highlighted some future directions of primary neuron culture in the next few decades.