Abstract
Microfluidic devices are now the most promising tool to mimic in vivo like scenarios such as tumorigenesis and metastasis due to its ability to more closely mimic cell's natural microenvironment (such as 3D environment and continuous perfusion of nutrients). In this study, the ability of 2% and 3% enzymatically crosslinked silk fibroin hydrogels with different mechanical properties are tested in terms of colorectal cancer cell migration, under different microenvironments in a 3D dynamic model. Matrigel is used as control. Moreover, a comprehensive comparison between the traditional Boyden chamber assay and the 3D dynamic microfluidic model in terms of colorectal cancer cell migration is presented. The results show profound differences between the two used biomaterials and the two migration models, which are explored in terms of mechanical properties of the hydrogels as well as the intrinsic characteristics of the models. Moreover, the developed 3D dynamic model is validated by demonstrating that hVCAM‐1 plays a major role in the extravasation process, influencing extravasation rate and traveled distance. Furthermore, the developed model 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.
Highlights
The developed 3D dynamic model is validated by demonstrating that hVCAM-1 plays a major role in the extravasation process, influencing extravasation rate and traveled distance
In our study, applying these concepts, we propose the use of a 3D dynamic model using a new biomaterial developed by our group: Horseradish peroxidase crosslinked silk fibroin hydrogels.[14] eSF hydrogels allow the tuning of mechanical properties and identify the most suitable stiffness to study cancer cell migration
The influence of polymer type and concentration of the used hydrogels was studied in terms of their rheological behavior in order to analyze the mechanical properties of the hydrogels
Summary
The ability of 2% and 3% enzymatically crosslinked silk fibroin hydrogels with different mechanical properties are tested in terms of colorectal cancer cell migration, under. Colorectal cancer (CRC) is a major cause of morbidity and mortality worldwide, and accounts for over 9% of all cancer incidence. A comprehensive comparison between the traditional Boyden chamber assay and the 3D dynamic microfluidic model in terms of colorectal cancer cell migration is presented. The developed model enables precise visualization of cancer cell migration within a 3D matrix in to unveil identification of cancer-causing agents in in vitro and in vivo animal models, as well as for the development of personalized therapies, drug screening, and to provide insightful knowledge on the mechanisms of tumor growth and metastasis.[2].
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