Xu Jie, Yang Shuangjia, Su Ya, Hu Xueyan, Xi Yue, Cheng Yuen Yee, Kang Yue, Nie Yi, Pan Bo, Song Kedong
State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, NSW 2007, Australia.
Int J Bioprint. 2022 Oct 28;9(1):630. doi: 10.18063/ijb.v9i1.630. eCollection 2023.
109Tissue-engineered scaffolds are more commonly used to construct three-dimensional (3D) tumor models for studies when compared to the conventional two-dimensional (2D) cell culture because the microenvironments provided by the 3D tumor models closely resemble the system and could achieve higher success rate when the scaffolds are translated for use in pre-clinical animal model. Physical properties, heterogeneity, and cell behaviors of the model could be regulated to simulate different tumors by changing the components and concentrations of materials. In this study, a novel 3D breast tumor model was fabricated by bioprinting using a bioink that consists of porcine liver-derived decellularized extracellular matrix (dECM) with different concentrations of gelatin and sodium alginate. Primary cells were removed while extracellular matrix components of porcine liver were preserved. The rheological properties of biomimetic bioinks and the physical properties of hybrid scaffolds were investigated, and we found that the addition of gelatin increased hydrophilia and viscoelasticity, while the addition of alginate increased mechanical properties and porosity. The swelling ratio, compression modulus, and porosity could reach 835.43 ± 130.61%, 9.64 ± 0.41 kPa, and 76.62 ± 4.43%, respectively. L929 cells and the mouse breast tumor cells 4T1 were subsequently inoculated to evaluate biocompatibility of the scaffolds and to form the 3D models. The results showed that all scaffolds exhibited good biocompatibility, and the average diameter of tumor spheres could reach 148.52 ± 8.02 μm on 7 d. These findings suggest that the 3D breast tumor model could serve as an effective platform for anticancer drug screening and cancer research .
与传统的二维细胞培养相比,组织工程支架更常用于构建三维(3D)肿瘤模型进行研究,因为3D肿瘤模型提供的微环境与体内系统非常相似,并且当将支架转化用于临床前动物模型时可以获得更高的成功率。通过改变材料的成分和浓度,可以调节模型的物理性质、异质性和细胞行为,以模拟不同的肿瘤。在本研究中,使用一种生物墨水通过生物打印制造了一种新型的3D乳腺肿瘤模型,该生物墨水由不同浓度的明胶和海藻酸钠与猪肝来源的脱细胞细胞外基质(dECM)组成。去除了原代细胞,同时保留了猪肝的细胞外基质成分。研究了仿生生物墨水的流变学性质和混合支架的物理性质,我们发现添加明胶增加了亲水性和粘弹性,而添加海藻酸钠增加了机械性能和孔隙率。膨胀率、压缩模量和孔隙率分别可达835.43±130.61%、9.64±0.41 kPa和76.62±4.43%。随后接种L929细胞和小鼠乳腺肿瘤细胞4T1,以评估支架的生物相容性并形成3D模型。结果表明,所有支架均表现出良好的生物相容性,7天时肿瘤球的平均直径可达148.52±8.02μm。这些发现表明,3D乳腺肿瘤模型可以作为抗癌药物筛选和癌症研究的有效平台。