Soft hydrogel-based architectures which allow the diffusion of solutes across the hydrogel matrix have been utilized to develop various functional systems by confining microorganisms. Recently, new hierarchical hydrogel structures have been pioneered to create multi-layered soft hydrogels in a concentric fashion to provide fundamental insights at the molecular level. Yet the strategies might not be standardized because different design considerations are required due to a wide range of chemical processes involved. At small scales, the fabrication of micro-size architectures requires higher reaction rates than that of macroscopic objects, which causes agglomeration between gels in a reaction bath. Only a few methods have been introduced to produce a single multi-layered capsule with diameters between 4 and 20 mm. Even with predictive mechanisms in various hydrogels, challenges exist in both mass production and scaling-down of the size of hydrogel architectures, and multi-layered techniques for cell encapsulation studies are even sparse. To address the challenges, we have developed a biocompatible model with robust design, utilizing alginate-based core-shell architectures. Herein, technical obstacles to create confined architectures for effective bacteria confinement have been resolved to retain functionally engineered cells inside the hydrogel architectures without disruption of the structures. Numerous small ecological systems in a hydrogel-based environment can be generated by recapitulating specific bacteria inside the conceived architecture. Microbial colonization occurs, ensuring cell longevity and production of molecules to serve as independent microbial modulators with direct or indirect activation of a response regulator by stimuli, including signaling molecules. To show the applicability of the platform, further, we demonstrate a reliable strategy with hydrogel-based confinement techniques to evaluate the concept of artificial natural habitats in developing bacteria-based functional systems (i.e., dynamic communication models, bacteria-mammalian cell interaction system, enzymatic bioreactors, etc.). We believe this approach has significant potential not only to study intra/multicellular complex communications in a highly specific manner but also to design a soft hydrogel-bead functional system.

Soft hydrogel microbial modulators and biological applications

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.