Title:

Microgel Production for Precision 3D Bioprinting Applications

Monodisperse gelatin microgels are a promising 3D bioprinting medium for producing biocompatible tissue-like structures with optimal architecture for facilitating multi-dimensional cell culture. Gelatin is a degraded form of collagen and serves as an ideal polymer for microgel synthesis as it contains cell adhesion peptides and creates an environment mimicking the characteristics of the extracellular matrix that promote cell proliferation. As opposed to bulk hydrogel which traps cells, a microgel-based bioink provides pore space to allow cells to grow, spread, and form cell-to-cell connections. Producing monodisperse microgels from gelatin has posed a challenge due to the temperature-dependent physical crosslinking of gelatin, making typical microfluidic methods difficult as gelatin solidifies at room temperature and clogs microfluidic channels. Bulk emulsion synthesis is the most common method for gelatin microgel production, but the process yields microgels of varying sizes which lead to nozzle clogging during 3D bioprinting. To produce monodisperse microgels, a microfluidic chip was produced by printing a sacrificial mold with the BioAssemblyBot 3D bioprinter and casting it in PDMS before bonding to a glass slide. This chip successfully produced monodisperse microgels composed of 2.5 wt% gelatin and 2.5 wt% GelMA, which were smaller on average than microgels produced by bulk emulsion and are optimal for cell-embedded 3D bioprinting.

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