Biomimetic and soft lab-on-a-chip platform based on enzymatic-crosslinked silk fibroin hydrogel for 3D cell co-culture

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<i>in vitro</i>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 (SF) hydrogels. Its unique mechano-chemical properties and high structural fidelity, make this platform especially suited for<i>in vitro</i>disease modelling, as demonstrated by reproducing the native dynamic 3D microenvironment of colorectal cancer and its response to chemotherapeutics in a simplistic way. Results show that from all the tested concentrations, 14 wt% enzymatically-crosslinked SF microfluidic platform has outstanding structural stability and the ability to perfuse fluid while displaying<i>in vivo</i>-like biological responses. Overall, this work shows a novel technique to obtain an enzymatically-crosslinked SF microfluidic platform that can be employed for developing soft lab-on-a-chip<i>in vitro</i>models.