Biomimetic and soft lab-on-a-chip platform based on enzymatic-crosslinked silk fibroin hydrogel for colorectal tumor model

Integrating biological material within soft microfluidic systems made of hydrogels offers countless possibilities in biomedical research to overcome the intrinsic limitations of traditional microfluidics based on solid, non-biodegradable, and non-biocompatible materials. Hydrogel-based microfluidic technologies have the potential to transform in vitro cell/tissue culture and modeling. However, most hydrogel-based microfluidic platforms are associated with device deformation, poor structural definition, reduced stability/reproducibility due to swelling, and a limited range in rigidity, which threatens their applicability. Herein, we describe a new methodological approach for developing a soft cell-laden microfluidic device based on enzymatically-crosslinked silk fibroin (eSF) hydrogels. Its unique mechano-chemical properties and high structural fidelity, make this platform especially suited for in vitro disease modelling, as demonstrated by reproducing the native dynamic 3D microenvironment of colorectal cancer and its response to chemotherapeutics. Results show that 14 wt% enzymatically-crosslinked silk fibroin microfluidic platform has outstanding structural stability and the ability to perfuse fluid while displaying in vivo-like biological responses. Overall, this work shows how the combination of enzymatically-crosslinked silk fibroin and microfluidics can be employed for developing soft lab-on-a-chip platforms with superior performance.