通过多支架组装方法对神经微环境进行3D建模。

3D modeling of neural microenvironment through a multi-scaffold assembly approach.

作者信息

Traldi Cecilia, Chiappini Vanessa, Chasseur Silvia, Aiello Federica, Boido Marina, Tonda-Turo Chiara

机构信息

Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.

POLITO BIOMedLAB, Politecnico di Torino, Turin, Italy.

出版信息

Mater Today Bio. 2025 Jul 14;33:102086. doi: 10.1016/j.mtbio.2025.102086. eCollection 2025 Aug.

Abstract

The engineering of 3D cell culture systems has emerged as promising approach to model central nervous system (CNS) intricacy with increasing physiological relevance. The fabrication of artificial microenvironments that closely resemble nervous tissue composition and architecture has provided useful substrates to promote neural cell growth and maturation under -like conditions; however, despite significant progress has been made in tissue mimicry, directing neural cell arrangement and connectivity in a controlled 3D environment remains extremely challenging. Here, we propose a novel approach that combines different biomaterials and biofabrication techniques to develop a multi-scaffold system mimicking distinctive features of the nervous tissue. Extrusion-based 3D bioprinting is employed to accurately position neural stem cells (NSCs) embedded in a gelatin methacryloyl hydrogel onto an aligned microfibrous polycaprolactone structure obtained by melt electrowriting. The hydrogel matrix successfully supports NSC growth within 3D bioprinted constructs, ensuring high cell viability and NSC differentiation into neuronal and glial phenotypes. Additionally, melt electrowriting technology allows the design of a microfibrous scaffold having well-defined geometry and aligned microporosity to replicate the anisotropic characteristics of nervous tissue. The inclusion of such scaffold in the 3D bioprinted system effectively steers neural cell organization in a 3D setting, guiding neural cell elongation in a preferred direction and promoting the establishment of a functional neural network. Our approach can be used to develop more sophisticated multicellular systems, possibly reassembling specific CNS circuits within a biomimetic microarchitecture, thus offering a versatile platform for the investigation of CNS functioning and pathology.

摘要

3D细胞培养系统工程已成为一种很有前景的方法,用于构建具有越来越高生理相关性的中枢神经系统(CNS)复杂性模型。制造与神经组织组成和结构极为相似的人工微环境,为在类似生理条件下促进神经细胞生长和成熟提供了有用的基质;然而,尽管在组织模拟方面取得了重大进展,但在可控的3D环境中引导神经细胞排列和连接仍然极具挑战性。在此,我们提出一种新颖的方法,该方法结合了不同的生物材料和生物制造技术,以开发一种模拟神经组织独特特征的多支架系统。基于挤出的3D生物打印技术被用于将包埋在甲基丙烯酰化明胶水凝胶中的神经干细胞(NSCs)精确地定位到通过熔体静电纺丝获得的排列整齐的微纤维聚己内酯结构上。水凝胶基质成功地支持了3D生物打印构建体中的NSC生长,确保了高细胞活力以及NSC向神经元和神经胶质细胞表型的分化。此外,熔体静电纺丝技术允许设计具有明确几何形状和排列整齐的微孔的微纤维支架,以复制神经组织的各向异性特征。将这种支架纳入3D生物打印系统可有效地在3D环境中引导神经细胞组织,引导神经细胞在优选方向上伸长并促进功能性神经网络的建立。我们的方法可用于开发更复杂的多细胞系统,可能在仿生微结构内重新组装特定的CNS回路,从而为研究CNS功能和病理学提供一个通用平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c76/12303067/7edfc3596755/ga1.jpg

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