Biomimetic and soft lab-on-a-chip platform based on
enzymatic-crosslinked silk fibroin hydrogel for colorectal tumor model
Mariana Carvalho
13B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal; ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal;
Corresponding Author:[email protected]
Author ProfileViviana Ribeiro
I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
Author ProfileDavid Caballero
I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
Author ProfileAbstract
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.