Three-dimensional (3D) gelatin based self-healing hydrogel as biomimetic co-culture model for colon tumor microenvironment study

• Main Author: Haryanto, Kelvin Renaldi
• Other Authors: Dalton Tay Chor Yong
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2020
• Subjects: Engineering
• Online Access: https://hdl.handle.net/10356/138845
• Institution: Nanyang Technological University

There is increasing evidence that cancer development and progression occurs in concert with alterations in the surrounding complex microenvironment, including abiotic stroma matrix and the myriad of stromal cell types. In order to better mimic the tumor microenvironment, the myriad of traditional co-culture systems has been developed, such as Transwell, microfluidic device, and tumor spheroids. However, there are some limitations in terms of their application, such as limited 2D culture setting, complicated isolation of different cell types, and labor-intensive. 3D self-healing hydrogel could become one of the alternatives as it allows more straightforward cell separation by cutting/healing process, cheap, and suitable for batch processing. Hence, we propose a double network self-healing hydrogel with gelatin-based as a cell culture scaffold, consist of additional Oxidized dextran (ODex) and gelatin methacryloyl (GelMA). The dynamic Schiff base formation between amine and aldehyde groups endows self-healing properties of the hydrogel, the stiffness of the hydrogel can be tuned via the second network crosslinking density of GelMA. The FTIR and gelation test results demonstrated that ODex and GelMA were successfully synthesized. Besides, hydrogel showed good self-healing ability after injection and incubation, indicating the critical role of the Schiff base bond. Upon rheological examination, mechanical properties and degradation of the hydrogel are found to be related with gelatin to GelMA ratio. Cytocompatibility results also align with the purpose of this project with high cell viability of DLD-1 and CAF. Nonetheless, continual studies need to be done on cancer cell co-culture conditions. Collectively, GelMA-ODex hydrogel shows the promising application as a scaffold of intricate cell co-culture design, tumor microenvironment study, and drug testing in the future.