Design of a hydrogel-based microfluidic chip for Organ-on-Chip applications

Abstract

Organ-on-chip is an emerging technology that combines microfluidic devices with 3D cell cultures to provide in vitro models that resemble the in vivo physiology of organs and tissues. These platforms can be used to understand the dysfunctions and pathogenesis of the body and to perform drug development and toxicology assays. Since in colorectal cancer the survival rate is very low when metastasis has occurred, the development of technologies that can be used to test new drugs and improve the prognosis of the disease is essential. Organ-on-chip can be used to model the tumor vascular microenvironment and provide a platform to understand the metastatic process by means of a vessel-on-chip, which would simulate the blood-vessel environment. However, current vessel-on-chip devices lack the translational capability to clinical outcomes. Therefore, in this project we aim to design, fabricate and validate a hydrogel-based microfluidic chip for in vitro modelling a blood vessel by embedding fibroblasts in the gel to recreate the surrounding extracellular matrix and support the later endothelial cell seeding in its walls. On the one hand, hot embossing technique was used to fabricate PMMA substrates of the chips. Screws and nuts were used to seal the devices to avoid the mixture of fluids in the outlets of the different channels and leakage. On the other hand, SLA 3D bioprinting approach was used to fabricate GelMA-PEGDA hydrogels that sustained the encapsulated fibroblasts. Different chip geometries were designed and validated including cell-laden hydrogels under flow conditions. Live/DeadTM assay was performed to assess cell viability of the encapsulated fibroblasts at different time points. Results shown that over 50% of the cells were alive after 7 days in culture in the chips, proving its feasibility, yet attributed to the lack of medium flow in the channels due to leakage. Even though further improvements are needed, this microfluidic device can be obtained using precise, low-cost and fast fabrication techniques and has offered promising results in terms of cell viability.