Aragón Institute of Nanoscience and Materials (INMA), CSIC-University of Zaragoza, Department of Organic Chemistry, C/Pedro Cerbuna 12, 50009 Zaragoza, Spain.
BEONCHIP S.L., CEMINEM, Campus Río Ebro. C/Mariano Esquillor Gómez s/n, 50018 Zaragoza, Spain.
J Mater Chem B. 2024 Mar 20;12(12):3144-3160. doi: 10.1039/d3tb02640j.
Biomimetic 3D models emerged some decades ago to address 2D cell culture limitations in the field of replicating biological phenomena, structures or functions found in nature. The fabrication of hydrogels for cancer disease research enables the study of cell processes including growth, proliferation and migration and their 3D design is based on the encapsulation of tumoral cells within a tunable matrix. In this work, a platform of gelatin methacrylamide (GelMA)-based photocrosslinked scaffolds with embedded colorectal (HCT-116) or pancreatic (MIA PaCa-2) cancer cells is presented. Prior to cell culture, the mechanical characterization of hydrogels was assessed in terms of stiffness and swelling behavior. Modifications of the UV curing time enabled a fine tuning of the mechanical properties, which at the same time, showed susceptibility to the chemical composition and crosslinking mechanism. All scaffolds displayed excellent cytocompatibility with both tumoral cells while eliciting various cell responses depending on the microenvironment features. Individual and collective cell migration were observed for HCT-116 and MIA PaCa-2 cell lines, highlighting the ability of the colorectal cancer cells to cluster into aggregates of different sizes governed by the surrounding matrix. Additionally, metabolic activity results pointed out to the development of a more proliferative phenotype within stiffer networks. These findings confirm the suitability of the presented platform of GelMA-based hydrogels to conduct 3D cell culture experiments and explore biological processes associated with colorectal and pancreatic cancer.
仿生 3D 模型在几十年前出现，旨在解决 2D 细胞培养在复制自然界中发现的生物现象、结构或功能方面的局限性。用于癌症研究的水凝胶的制造能够研究细胞过程，包括生长、增殖和迁移，并且它们的 3D 设计基于在可调节基质中封装肿瘤细胞。在这项工作中，提出了一种基于明胶甲基丙烯酰胺（GelMA）的光交联支架的平台，其中嵌入了结肠直肠（HCT-116）或胰腺（MIA PaCa-2）癌细胞。在细胞培养之前，根据刚度和溶胀行为评估水凝胶的机械特性。UV 固化时间的修改实现了对机械性能的微调，同时显示出对化学成分和交联机制的敏感性。所有支架都显示出与两种肿瘤细胞的良好细胞相容性，同时根据微环境特征引起不同的细胞反应。观察到 HCT-116 和 MIA PaCa-2 细胞系的单个和集体细胞迁移，突出了结肠直肠癌细胞能够根据周围基质聚集形成不同大小的聚集体的能力。此外，代谢活性结果指出，在更刚性的网络中发展出更具增殖表型的能力。这些发现证实了所提出的基于 GelMA 的水凝胶平台适合进行 3D 细胞培养实验，并探索与结肠直肠癌和胰腺癌相关的生物学过程。
