Theranostic Probiotic Engineered Living Materials That Dynamically Respond to Inflammation Markers.

Abstract

The development of smart, implantable devices localized at the site of inflammation to conditionally and proactively combat active inflammation for inflammatory bowel disease (IBD), has the potential to transform the patient's quality of life compared to conventional treatment modalities. Engineered probiotic organisms can enable dynamic production of therapeutic compounds in response to inflammatory biomarkers. However, delivery and localization of these engineered organisms to the site of inflammation requires their integration into a material or device that sustains their viability and metabolic activity. To this end, a 3D printed engineered living material (ELM) is developed using an engineered probiotic organism (E. coli Nissle 1917) with genetic circuits to sense biomarkers for inflammation and respond with the production of anti-inflammatory compounds. These organisms are incorporated into poly(ethylene glycol) diacrylate (PEGDA) resins for the light-based 3D printing of 3D constructs. The organisms are physically encapsulated within the PEGDA and are fully viable and metabolically active. The 3D printed ELM devices are able to detect clinically relevant amounts of nitric oxide as an inflammatory biomarker and respond with the production of tryptamine or 1-acetyl-3-carboxyl-β-carboline as representative anti-inflammatory agents. Additionally, the ELM devices are efficacious in treating in vitro models of inflammation, including murine macrophages and intestinal epithelial cells. Looking forward, these ELM devices could serve as theranostic modalities for the long-term treatment of inflammatory disorders such as IBD.