Buckling Microchannels of Porous Hydrogel Films for Vessel-on-a-Chip Fabrication

The trend in constructing 3D human tissue/organ models in vitro for developing accurate diagnosis and effective treatments has been gaining momentum in recent years in a wide range of biological research fields, such as tissue engineering, biomedicine, and drug discovery. Here, hydrogel-based microchannels with high water content have recently attracted attention as an alternative platform that can faithfully reproduce the natural in vivo environment with high biocompatibility, ex vivo matrix (ECM)-like elastic modulus, permeability of bioactive substances, and biomimetic motion through stimuli-responsiveness.<br/>We have previously reported a fabrication method in which the swelling of a common polyacrylamide (PAAm) hydrogel film is controlled on a support substrate to fabricate microchannel in an easy-to-use manner.[1] The method is based on the swelling of the laminate, with the interface between the PAAm hydrogel film and the support substrate given an arbitrary adhesion/non-adhesion pattern. Swelling-induced pressure selectively delaminates and buckles the hydrogel on the non-adhesive region, forming a space between the hydrogel and the support substrate that can be used as a microchannel. By using PAAm hydrogel with a high polymer concentration, this thin-film, tubular microchannel structure, similar to that of blood vessels and gastrointestinal tracts, is strong enough and flexible enough to withstand large deformations under pressure, even with film thicknesses less than 100 μm.[2] In addition, it can be made to reproduce intestinal peristalsis/segmentation by utilizing stimuli-responsive hydrogels, and thus, it may be a highly expandable platform that can mimic the dynamic stimulation environment of a living body.[3] However, while a high polymer concentration is an important factor in creating a tough and functional hydrogel, the high density of the hydrogel mesh reduces the permeability of the material.<br/>In this study, we propose a novel and versatile method that couples cononsolvency photopolymerization, which enables the incorporation of porous structures into hydrogels, with on-chip microchannels formed by buckling of a thin film. This method provides a hydrogel-based microchannel with improved permeability while maintaining its mechanical properties by incorporating a continuous porous structure into a synthetic polymer network with excellent mechanical properties and easy functionalization. Specifically, the open-porous PAAm hydrogel fabricated by cononsolvency photopolymerization exhibited nearly five times better permeability than those of conventional PAAm hydrogels and was comparable to other materials commonly used as substrates for hydrogel-based microchannels. Furthermore, by coating the permeable microchannel with vascular endothelial cells, we proved the feasibility of evaluating the barrier function, fabricating a variety of channel geometries, and developing the technique into a co-culture system. Both the cononsolvency photopolymerization and on-chip structure formation methods used in this research are universal ones based on physical phenomena, so they can be used for various other types of swellable functional hydrogels. Therefore, we believe that the vast library of synthetic hydrogels can be used for fabricating microfluidic platforms that have the appropriate physical properties, responsiveness, and chemical composition for the target tissue/organ.<br/><br/>[1] R. Takahashi, et al. ACS Appl. Mater. Interfaces, 2019, 11, 28267.<br/>[2] R. Takahashi, et al. Lab Chip, 2021, 21, 1307.<br/>[3] R. Takahashi, et al. Adv. Funct. Mater, 2023, 33, 2300184.