Investigating physical properties of hybrid hyaluronic acid and collagen compositions of GelMA microgels toward tissue engineering and organ-on-chip applications

Abstract

Microgels are promising tools in biomedical sciences to be utilized as 3D cell culture scaffolds and cell-delivery or drug-delivery vehicles. Carrying the desired properties of hydrogels, they can be fabricated from various materials in different shapes and sizes. Additionally, due to their increased surface-to-volume ratio, they provide fast nutrient, waste, and species transport with altered solute–material interactions. Despite their micrometer size and the differentiated behaviors that come with these properties, the characterization methods utilized so far to investigate their physical and morphological properties are majorly carried out on their bulk versions, resulting in inaccurate estimates and somewhat missed information. Here, in this work, swelling, degradation, and morphological examination assays curated for microgels are proposed to reflect the actual behavior of microgels. Accordingly, gelatin methacryloyl, complemented with hyaluronic acid methacrylate and collagen to set an example of different types of polymer networks, was fabricated into microgels using a droplet microfluidic platform with in situ photopolymerization. An easy washing and drying process is proposed as a substitution for the harsh conditions of lyophilization for morphological analysis, resulting in a much more accurate picture of the porous structures. Swelling and enzymatic degradation assays, usually done by immersing a bulk hydrogel in a medium for an extended period, are substituted with swelling and degrading individual microgels in a custom-made platform that enables real-time, statistically significant data acquisition. Results showed that, due to their small size, swelling occurs in a matter of minutes, with different temporal profiles depending on the medium and microgel compositions, and enzymatic degradation takes place in a couple of hours with varying behaviors, changing due to the polymers, enzyme type, and concentration. Overall, this work highlights the necessity and importance of characterizing microgels in their respective sizes, hopefully advancing their utilization in microphysiological systems and biomedical applications.