Implantable Living Materials Autonomously Deliver Therapeutics from Contained Engineered Bacteria

Abstract

Microbes are increasingly utilized as living therapeutic vehicles, yet their uncontrolled dissemination in the body has long remained a roadblock to clinical development. Physical containment, while widely used for mammalian cells, remains largely unattainable due to eventual bacteria escape. Here, we present an implantable material platform that encapsulates and confines bacteria, wherein synthetically engineered microbes produce therapeutic payloads from within. To prevent microbial escape, we developed a hydrogel scaffold with dual mechanical features: high stiffness to regulate bacterial proliferation and high toughness to resist material fracture under physiological stress. This design achieved complete bacterial containment for over six months and withstood multiple forms of mechanical loading that otherwise caused catastrophic material failure. By genetically engineering embedded bacteria, we endowed the material with environmental sensing and on-demand therapeutic release capabilities and demonstrated autonomous treatment in a murine prosthetic joint infection model. This multimodal strategy provides a safe and generalizable framework for deploying microbial medicines in vivo and supports their use as autonomous drug depots across a range of disease settings.