Living Bacterial Hydrogels as Therapeutic Biomaterials
July 14-18, 2019
Engineered living materials (ELMs) are growing in interest as they offer the potential to combine the biosynthetic potential of living organisms with the properties of functional materials. ELM research requires the control of a cellular chassis, which can draw resources from the environment and use them to grow macroscopic materials. ELMs are of particular interest to treat and diagnose diseases in the gastrointestinal (GI) tract. In the gut, probiotic bacteria can be used as living factories to produce a living extracellular matrix with tunable mechanical, chemical and biological properties. Specifically, here we report the fabrication of living bacterial hydrogels that can be delivered to the gut and that display mucoadhesive properties. Living bacterial hydrogels are simply produced by concentrating a biofilm-producing bacterial culture on a membrane via vacuum filtration, to collect a viscous product. Extracellular matrix proteins confer the hydrogel its mechanical properties, which can be tuned by genetically modifying the composition and structure of the proteins. In this work, we have engineered self-assembling CsgA proteins, the main subunit of extracellular curli fibers, to tune the adhesive and viscoelastic properties of the gels. We have fused trefoil factors, small mucoadhesive proteins, to the CsgA subunits to produce the engineered therapeutic hydrogels. We have shown that the living hydrogels can adhere to the inner layer of the gut and self-regenerate, both in vitro and in vivo. Since the curli fibers these hydrogels are highly versatile and can be genetically modified to display a variety of fusion proteins, customizing the properties of the bacterial hydrogels opens up many potential diagnostic and therapeutic applications. Such living gels and biofilms could be used to fill lesions in the GI musoca layer, to track microorganisms in the gut, or to locally deliver small molecules or drugs.
Noemie-Manuelle Dorval Courchesne, "Living Bacterial Hydrogels as Therapeutic Biomaterials" in "Biochemical and Molecular Engineering XXI", Christina Chan, Michigan State University, USA Mattheos Koffas, RPI, USA Steffen Schaffer, Evonik Industries, Germany Rashmi Kshirsagar, Biogen, USA Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/biochem_xxi/125