Chen Zaozao, Wang Fei, Zhang Jie, Sun Xiaowei, Yan Yuchuan, Wang Yan, Ouyang Jun, Zhang Jing, Honore Tess, Ge Jianjun, Gu Zhongze
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
Institute of Biomaterials and Medical Devices, Southeast University, Suzhou, China.
Front Bioeng Biotechnol. 2020 Dec 22;8:611796. doi: 10.3389/fbioe.2020.611796. eCollection 2020.
A major factor for developing new tumor models is to recreate a proper three-dimensional environment for 3D tumors culture. In this 3D microenvironment, extracellular matrices play important roles in regulation of hallmark features of cancer through biochemical and mechanical signals. The fabrication of a mechanical and biophysical controllable hydrogel, while sharing similarities with Matrigel in cancer invasiveness evaluation, is an urgent but unmet need. In this study, we developed a hybrid hydrogel system composed of GelMA and hydrolyzed collagen to model tumor micro-environment and tested with several cancer cells with different origin and characteristics. This hydrogel possesses a well-ordered homogenous microstructure, excellent permeability and an adjustable mechanical stiffness. This hydrogel demonstrated similar properties as Matrigel in tumor spheroids culture and 3D tumor invasiveness studies. It was further applied in a Tumor-on-a-Chip system with 3D-bioprinting. Our research demonstrated this hydrogel's effectiveness in tumor 3D culture, and its potential to replace Matrigel in cancer invasiveness evaluation.
开发新的肿瘤模型的一个主要因素是为三维肿瘤培养重建一个合适的三维环境。在这个三维微环境中，细胞外基质通过生化和机械信号在调节癌症的标志性特征中发挥重要作用。制造一种机械和生物物理可控的水凝胶，虽然在癌症侵袭性评估方面与基质胶有相似之处，但却是一个迫切但未得到满足的需求。在本研究中，我们开发了一种由甲基丙烯酰化明胶（GelMA）和水解胶原蛋白组成的混合水凝胶系统来模拟肿瘤微环境，并对几种具有不同来源和特征的癌细胞进行了测试。这种水凝胶具有有序的均匀微观结构、优异的渗透性和可调节的机械刚度。这种水凝胶在肿瘤球体培养和三维肿瘤侵袭性研究中表现出与基质胶相似的特性。它进一步应用于具有三维生物打印的芯片上肿瘤系统。我们的研究证明了这种水凝胶在肿瘤三维培养中的有效性，以及在癌症侵袭性评估中替代基质胶的潜力。
