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 countlesspossibilities in biomedical research to overcome the intrinsic limitations of traditionalmicrofluidics based on solid, non-biodegradable, and non-biocompatible materials.Hydrogel-based microfluidic technologies have the potential to transformin vitrocell/tissueculture and modeling. However, most hydrogel-based microfluidic platforms are associated withdevice deformation, poor structural definition, reduced stability/reproducibility due to swelling,and a limited range in rigidity, which threatens their applicability. Herein, we describe a newmethodological approach for developing a soft cell-laden microfluidic device based onenzymatically-crosslinked silk fibroin (SF) hydrogels. Its unique mechano-chemical properties andhigh structural fidelity, make this platform especially suited forin vitrodisease modelling, asdemonstrated by reproducing the native dynamic 3D microenvironment of colorectal cancer andits response to chemotherapeutics in a simplistic way. Results show that from all the testedconcentrations, 14 wt% enzymatically-crosslinked SF microfluidic platform has outstandingstructural stability and the ability to perfuse fluid while displayingin vivo-like biological responses.Overall, this work shows a novel technique to obtain an enzymatically-crosslinked SF microfluidicplatform that can be employed for developing soft lab-on-a-chipin vitro models.