A living hydrogel platform for wireless light-controlled microbial therapy in the stomach.
TL;DR
A rapidly assembled and remotely programmable living bioelectronic interface by combining photocrosslinkable biomaterials, optogenetic engineering, wearable electronics, and engineered microbes is established, offering a controllable approach for microbial therapy of gastrointestinal diseases.
Abstract
Engineered microbial therapies provide a promising strategy for in situ production of therapeutic molecules at disease sites; however, their clinical translation remains limited by insufficient retention at target tissues and the lack of external control after administration. Here, we develop a wearable bioelectronic-assisted living hydrogel platform that enables rapid in situ immobilization and remote regulation of engineered bacteria. Optogenetically engineered bacteria capable of green-light-induced anti-interleukin-6 (anti-IL-6) secretion were encapsulated within a photoresponsive Gelatin Methacryloyl/Sodium Alginate (GelMA/SA) hydrogel precursor. Upon external green-light stimulation, the precursor rapidly transformed into a stable living hydrogel within 5 s while activating the therapeutic protein expression program of engineered bacteria, thereby coordinating hydrogel formation with microbial functional regulation. This rapid in situ gelation strategy enhanced bacterial retention in the stomach and provided a protective microenvironment to maintain bacterial viability and sustained functional output. Combined with a lightweight wireless-powered wearable LED device, the system allowed non-invasive optical control after gastric administration, overcoming the limited spatiotemporal controllability of conventional microbial therapies. The platform preserved bacterial activity, enabled on-demand modulation of inflammatory responses, and demonstrated therapeutic benefits in full-thickness skin wound and ethanol-induced gastritis models. Compared with bacteria or hydrogel treatment alone, optically activated bacterial therapy further reduced inflammation and promoted tissue repair. This work establishes a rapidly assembled and remotely programmable living bioelectronic interface by combining photocrosslinkable biomaterials, optogenetic engineering, wearable electronics, and engineered microbes, offering a controllable approach for microbial therapy of gastrointestinal diseases.