Macroencapsulated bacteria for in vivo sensing and therapeutics

Engineered bacteria are increasingly recognized as sustained and intelligent sources for sensing and therapeutics due to their unique capabilities such as in situ multiplication, tissue targeting, and genetic editability. However, the clinical applications of these living agents are hindered by the ineffective immunoisolation, residency, and removal against the complex and dynamic in vivo environment. Existing approaches focus on surface decoration and encapsulation of engineered bacteria, or "microencapsulation," but there are limits to what can be achieved with modifications of bacteria themselves. An emerging strategy combines millimeter- to centimeter-scale engineered devices and systems with bacteria, or "macroencapsulation," offering unique advantages such as extending the in vivo lifetime and engraftment of bacteria, enhancing immunoisolation, and enabling real-time signal readouts via wireless electronic technologies. In this review, the design rationales for macroencapsulated bacteria toward in vivo applications are discussed, and examples in bacterial devices for transdermal and oral applications are highlighted. Since the gastrointestinal tract represents a major site for engineered bacteria, we also summarize and compare various strategies for synthetic engraftment of orally administered encapsulated bacteria.