Highly Strong and Transparent Hydrogel Elastomers Microfabricated for 3D Microphysiological Systems

Abstract 3D microarchitected hydrogels have recently been exploited to establish microphysiological systems for preclinical studies. However, promising hydrogels, unlike anhydrous elastomers, which have been widely adopted for device microfabrication, are still scarce for biodevice engineering due to their limitations in mechanical properties and manufacturability. Here, we leverage temperature-controlled physical cross-linking of a polymer network to generate highly strong, elastic, and transparent hydrogels, which can be further readily microfabricated into elaborate constructs for diverse device designs. Specifically, with the addition of a good solvent of dimethyl sulfoxide, poly(vinyl alcohol) dissolved in the mixed solvent of dimethyl sulfoxide/water (4:1) shows extensive physical cross-links of nanosized polymeric crystallites upon one single freeze–thaw cycle, leading to the resulting hydrogels (∼80% water content) with superior mechanical properties and optical transparency, comparable to or even exceeding the anhydrous elastomer of polydimethylsiloxane. Furthermore, the simple processing technologies enable the patterning of hydrogels (high resolution of 20 μm) customized for various in vitro models, as exemplified by hydrogel microwell arrays supporting efficient tumor-spheroid generation and hydrogel microchannels lined with a confluent endothelial monolayer. This approach to fabricating microphysiological systems on hydrogel platforms will provide new avenues for technological innovation in disease models, organ-on-a-chip, and personalized medicine.