In Situ Production and Continuous Delivery of Therapeutics by 3D-Printed Engineered Living Materials

The goal of this research is to develop 3D printed hydrogel composites comprising a polymer network laden with metabolically engineered microorganisms capable of continuously and indefinitely eluting a biosynthesized therapeutic or bioactive agent. We envision using these engineered living materials (ELMs) as devices for local drug delivery in the treatment of malignancies or inflammatory diseases affecting the gastrointestinal epithelium. While our ELM platform is applicable to a broad array of microorganisms that include yeast and bacteria, we have chosen to focus on engineered variants of E. coli Nissle 1917, a commensal strain of bacteria common within the gut microbiome. Using a microorganism native to the human microbiome may facilitate translation of our platform to treat gastrointestinal diseases. The outcomes of this work will advance the field of drug delivery by providing a fundamentally unique delivery platform which enables in situ biocatalytic production of therapeutics. Additionally, the use of ELMs in drug delivery devices will provide new insight for drug manufacturing approaches. We anticipate that these versatile materials will ultimately afford a transformational technology that could be used in a variety of medical devices that include stents, microneedles and other local drug delivery devices.