Temperature-responsive biometamaterials for gastrointestinal applications.

Abstract

We hypothesized that ingested warm fluids could act as triggers for biomedical devices. We investigated heat dissipation throughout the upper gastrointestinal (GI) tract by administering warm (55°C) water to pigs and identified two zones in which thermal actuation could be applied: esophageal (actuation through warm water ingestion) and extra-esophageal (protected from ingestion of warm liquids and actuatable by endoscopically administered warm fluids). Inspired by a blooming flower, we developed a capsule-sized esophageal system that deploys using elastomeric elements and then recovers its original shape in response to thermal triggering of shape-memory nitinol springs by ingestion of warm water. Degradable millineedles incorporated into the system could deliver model molecules to the esophagus. For the extra-esophageal compartment, we developed a highly flexible macrostructure (mechanical metamaterial) that deforms into a cylindrical shape to safely pass through the esophagus and deploys into a fenestrated spherical shape in the stomach, capable of residing safely in the gastric cavity for weeks. The macrostructure uses thermoresponsive elements that dissociate when triggered with the endoscopic application of warm (55°C) water, allowing safe passage of the components through the GI tract. Our gastric-resident platform acts as a gram-level long-lasting drug delivery dosage form, releasing small-molecule drugs for 2 weeks. We anticipate that temperature-triggered systems could usher the development of the next generation of stents, drug delivery, and sensing systems housed in the GI tract.