Novel Fabrication Technique to Confine Hydrogels with Different Patterns inside Microfluidic Devices without Pillars

In the field of microtechnologies applied to the simulation of controlled biological environments are the so-called organ-on-a-chip, microfluidic cell culture devices. The gradient model plays an indispensable role in this technology. Here, we present a novel microfabrication process for pillarless microfluidic platforms which enables the creation of gradients inside them

Impact of tumour microenvironment stiffness on immune cell behaviour using Organ-on-chip models

The extracellular matrix (ECM) is one of the main factors that are modified by glioblastoma. The tumour is able to increase the stiffness of the ECM, hindering the infiltration of the immune system into the tumour. Simulating this whole network is a difficult task to accomplish in conventional cellular models. Therefore, this study uses organ-on-chip devices to simulate the tumour microenvironment and study the effect of ECM stiffness on immune cell behaviour

Reducing Inert Materials for Optimal Cell–Cell and Cell–Matrix Interactions within Microphysiological Systems

In the pursuit of achieving a more realistic in vitro simulation of human biological tissues, microfluidics has emerged as a promising technology. Organ-on-a-chip (OoC) devices, a product of this technology, contain miniature tissues within microfluidic chips, aiming to closely mimic the in vivo environment. However, a notable drawback is the presence of inert material between compartments, hindering complete contact between biological tissues. Current membranes, often made of PDMS or plastic materials, prevent full interaction between cell types and nutrients. Furthermore, their non-physiological mechanical properties and composition may induce unexpected cell responses. Therefore, it is essential to minimize the contact area between cells and the inert materials while simultaneously maximizing the direct contact between cells and matrices in different compartments. The main objective of this work is to minimize inert materials within the microfluidic chip while preserving proper cellular distribution. Two microfluidic devices were designed, each with a specific focus on maximizing direct cell–matrix or cell–cell interactions. The first chip, designed to increase direct cell–cell interactions, incorporates a nylon mesh with regular pores of 150 microns. The second chip minimizes interference from inert materials, thereby aiming to increase direct cell–matrix contact. It features an inert membrane with optimized macropores of 1 mm of diameter for collagen hydrogel deposition. Biological validation of both devices has been conducted through the implementation of cell migration and cell-to-cell interaction assays, as well as the development of epithelia, from isolated cells or spheroids. This endeavor contributes to the advancement of microfluidic technology, aimed at enhancing the precision and biological relevance of in vitro simulations in pursuit of more biomimetic models

Tuneable hydrogel patterns in pillarless microfluidic devices

Organ-on-chip (OOC) technology has recently emerged as a powerful tool to mimic physiological or pathophysiological conditions through cell culture in microfluidic devices. One of its main goals is bypassing animal testing and encouraging more personalized medicine. The recent incorporation of hydrogels as 3D scaffolds into microfluidic devices has changed biomedical research since they provide a biomimetic extracellular matrix to recreate tissue architectures. However, this technology presents some drawbacks such as the necessity for physical structures as pillars to confine these hydrogels, as well as the difficulty in reaching different shapes and patterns to create convoluted gradients or more realistic biological structures. In addition, pillars can also interfere with the fluid flow, altering the local shear forces and, therefore, modifying the mechanical environment in the OOC model. In this work, we present a methodology based on a plasma surface treatment that allows building cell culture chambers with abutment-free patterns capable of producing precise shear stress distributions. Therefore, pillarless devices with arbitrary geometries are needed to obtain more versatile, reliable, and biomimetic experimental models. Through computational simulation studies, these shear stress changes are demonstrated in different designed and fabricated geometries. To prove the versatility of this new technique, a blood–brain barrier model has been recreated, achieving an uninterrupted endothelial barrier that emulates part of the neurovascular network of the brain. Finally, we developed a new technology that could avoid the limitations mentioned above, allowing the development of biomimetic OOC models with complex and adaptable geometries, with cell-to-cell contact if required, and where fluid flow and shear stress conditions could be controlled