Microfluidics: Tuning Enzymatically Crosslinked Silk Fibroin Hydrogel Properties for the Development of a Colorectal Cancer Extravasation 3D Model on a Chip (Global Challenges 5‐6/2018)

Abstract

In order to win the battle against cancer, further advances are needed to unveil identification of cancer-causing agents in in vitro and in vivo animal models, as well as for the development of personalized therapies and drug screening. They provide insightful knowledge on the mechanisms of tumor growth and metastasis. Therefore, the transition from 2D to 3D models, comprising the integration of tissue engineering (TE) strategies with microfluidic technologies, have sparked a breakthrough in the design of in vitro microfluidic culture models. Microfluidic devices are now one of the most promising tools to mimic in-vivo-like conditions, either in normal or disease scenarios such as tumorigenesis or pathogenesis. They can provide useful model systems to investigate complex phenomena under combination of multiple controllable biochemical and biophysical microenvironments when coupled with high resolution real-time imaging. The commercially available microfluidic chip used in this study enables precise visualization of cancer cell migration within a 3D matrix in response to microenvironmental cues, shedding light on the importance of biophysical properties in cell behavior. The developed model employs enzymatically crosslinked silk fibroin hydrogels to access cancer cell migration in response to hVCAM-1, a molecule that has a major role in the extravasation process. This is precisely what is being observed in the zoom-in image: red-stained colorectal cancer cells migrating from the top of the channel towards the inside of the extracellular matrix-like silk hydrogel. Further details can be found in article number 1700100 by Joaquim M. Oliveira and co-workers.