Liu Xinyue, Shu Yan, Zhu Jingjing, Fang Huan, Su Ya, Ma Hailin, Li Bing, Xu Jie, Cheng Yuen Yee, Pan Bo, Song Kedong
Cancer Hospital of Dalian University of Technology, State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
Cancer Hospital of Dalian University of Technology, State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
Int J Biol Macromol. 2025 Mar;293:139346. doi: 10.1016/j.ijbiomac.2024.139346. Epub 2024 Dec 30.
Colorectal cancer (CRC) is now the third most common cancer worldwide. However, the development cycle for anticancer drugs is lengthy and the failure rate is high, highlighting the urgent need for new tumor models for CRC-related research. The decellular matrix (dECM) offers numerous cell adhesion sites, proteoglycan and cytokines. Notably, porcine small intestine is rich in capillaries and lymphatic capillaries, which facilitates nutrient absorption. This study, we utilized dECM, along with methylacryloyl gelatin (GelMA), sodium alginate (SA) and nanoclay (NC) to create a hydrogel scaffold through 3D extrusion bioprinting. Human CRC cells (HCT8) were seeded onto the scaffold and their drug resistance was tested using 5-fluorouracil (5-FU). Our findings indicate that dECM enhances the hydrophilic properties, mechanical strength and biocompatibility of the scaffold. Furthermore, compared to traditional two-dimensional (2D) models, the three-dimensional (3D) scaffold supports the long-term growth of tumor spheres. After 2 days of 5-FU treatment, the cell survival rate reaches 88.06 ± 0.51 %. This suggests that our scaffold provides a promising alternative platform for in vitro research on cancer mechanisms, anti-cancer drug screening and new drug development.
结直肠癌（CRC）现已成为全球第三大常见癌症。然而，抗癌药物的研发周期漫长且失败率高，这凸显了对用于CRC相关研究的新肿瘤模型的迫切需求。去细胞基质（dECM）提供了众多细胞粘附位点、蛋白聚糖和细胞因子。值得注意的是，猪小肠富含毛细血管和毛细淋巴管，这有利于营养吸收。在本研究中，我们利用dECM，结合甲基丙烯酰化明胶（GelMA）、海藻酸钠（SA）和纳米粘土（NC），通过3D挤出生物打印创建了一种水凝胶支架。将人CRC细胞（HCT8）接种到支架上，并使用5-氟尿嘧啶（5-FU）测试其耐药性。我们的研究结果表明，dECM增强了支架的亲水性、机械强度和生物相容性。此外，与传统的二维（2D）模型相比，三维（3D）支架支持肿瘤球的长期生长。在5-FU处理2天后，细胞存活率达到88.06±0.51%。这表明我们的支架为癌症机制的体外研究、抗癌药物筛选和新药开发提供了一个有前景的替代平台。
