3D bioprinting of living materials represents an interesting paradigm toward the efficacy enhancement for the biosynthesis of various functional compounds in microorganisms. Previous studies have shown the success of 3D-printed bioactive systems in the production of small molecular compounds. However, the feasibility of such a strategy in producing macromolecules and how the geometry of the 3D scaffold influences the productivity are still unknown. In this study, we printed a series of 3D gelatin-based hydrogels immobilized with fermentation bacteria that can secrete hyaluronic acid (HA), a very useful natural polysaccharide in the fields of biomedicine and tissue engineering. The 3D-printed bioreactor was capable of producing HA, and an elevated yield was obtained with the system bearing a grid structure compared to that either with a solid structure or in a scaffold-free fermentation condition. As for the grid structure, bioreactors with a 90° strut angel and a median interfilament distance displayed the highest HA yield. Our findings highlighted the significant role of 3D printing in the spatial control of microorganism-laden hydrogel structures for the enhancement of biosynthesis efficiency.
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