Investigators explore temperature-triggered devices for gastrointestinal therapies

April 17, 2019

Gastrointestinal devices such as stents, endoscopic tubes, balloons and drug delivery systems can help clinicians treat patients with a range of conditions. But currently available methods for triggering where and when drugs are released or when a device is triggered to disassemble or change shape are often slow, which can restrict the utility of such tools. Investigators from Brigham and Women's Hospital and MIT are designing devices that can be triggered by the ingestion of a warm liquid to break down into smaller segments that can be excreted. In proof-of-concept experiments in preclinical models, the team tested two devices -- one that could be induced to change conformation in the esophagus to exit following the delivery of a drug, and the other that could reside unperturbed in the stomach until intentionally triggered. The team's results are published in Science Translational Medicine.

"We are intrigued by a simple question: when you ingest a hot liquid, what happens as it travels down your esophagus and into the stomach?" said co-corresponding author C. Giovanni Traverso, MB, BChir, PhD, a gastroenterologist and biomedical engineer in the Division of Gastroenterology at the Brigham. "What we've found is that there are essentially two zones -- the esophageal and the gastric -- which means that we may be able to control and trigger gastrointestinal devices in these two regions with precision using warm water."

The first device the team tested was inspired by a blooming flower. This capsule-sized esophageal system with petal-like structures can close up like a bud when a warm fluid is ingested. The prototype, which was tested in pigs, unfurled in the esophagus, making contact with the esophageal wall and releasing milli-needles loaded with model drugs. When warm water was administered, the prototype fully closed and passed from the esophagus into the stomach.

The second device tested was a highly flexible, gastric resident device capable of releasing drug of extended-- a device intended to stay in the stomach and release a regular dosage of a drug for weeks. Ingesting a warm liquid did not disturb the functioning of the device, but directly spraying warm water into the stomach with the aid of endoscope helped break down the device into pieces that could safely pass through the gastrointestinal tract in the pig model.

"Our approach was to employ design principles of transformable architected materials (mechanical metamaterials) whose shape and volume can be considerably altered through thermal actuation, as a new approach for developing gastrointestinal (GI) technologies with fast and robust response," said first author Sahab Babaee, a postdoctoral associate in the Langer Lab at MIT.

The authors note that the current work provides a proof of concept, but additional testing will be needed to characterize heat dissipation in humans. The team is currently identifying and prioritizing conditions to optimize this new approach for where it is needed most.

"Currently, many gastric devices need to be removed by pulling them out through the esophagus. We anticipate that temperature-triggered systems could usher in the development of the next generation of stents, drug delivery and sensing systems housed in the gastrointestinal tract," said Traverso.
-end-
Co-authors of this work include: Simo Pajovic, Ameya R. Kirtane, Jiuyun Shi, Ester Caffarel-Salvador, Kaitlyn Hess, Joy E. Collins, Siddartha Tamang, Aniket V. Wahane, Alison M. Hayward, Hormoz Mazdiyasni and Robert Langer.

Funding for this work was provided by the Bill and Melinda Gates Foundation (grant numbers OPP1139921 and OPP1139937) and NIH grant EB000244. Several co-authors are co-inventors on provisional application numbers 62/767,749, 62/767,954, and 62/767,798, filed by MIT related to this work. Complete details of all relationships for profit and not for profit for Traverso can be found here. A list of entities with which Langer is involved, compensated, or uncompensated, can be found here.

Paper cited: Babaee, S et al. "Temperature-responsive biometamaterials for gastrointestinal applications" Science Translational Medicine DOI: 10.1126/scitranslmed.aau8581

Brigham and Women's Hospital

Related Stents Articles from Brightsurf:

3D printed stents that treat inflammation
POSTECH Professor Dong-Woo Cho's research team develops bioink-loaded esophageal stents for treating radiation esophagitis.

Study could be first step in providing personalized care to patients with ureteral stents
Published today in Cell Reports Medicine, researchers at Lawson Health Research Institute and Western University conducted a novel microbiome study to examine bacteria associated with ureteral stents.

Two paths better than one for treating patients with heart stents
Pairing a blood-thinning drug with aspirin daily for patients who have an angioplasty with a stent can contribute to better health outcomes, including lower risk of death, than aspirin alone, according to a recent study by cardiologists at the University of Alberta and Mazankowski Alberta Heart Institute.

Open heart surgery outperforms stents in patients with multivessel disease
Coronary artery bypass grafting (CABG) surgery may be the best treatment option for most patients with more than one blocked heart artery, according to research published today in The Annals of Thoracic Surgery, published by Elsevier.

For infants with heart disease, are shunts or stents better to maintain blood flow?
Infants with various forms of congenital heart disease require a stable source of blood flow to their lungs in order to survive until a more definitive operation can be performed.

3-D-printed polymer stents grow with pediatric patients and biodegrade over time
A new study demonstrates proof-of-concept for combining computational design and simulation tools with 3-D printing technology to produce self-expandable polymer stents that can grow with pediatric patients, are biodegradable, and require only a minimally-invasive procedure for implantation.

Cardiologist warns against dissolvable stents in NEJM
In a New England Journal of Medicine (NEJM) editorial published last week, Debabrata Mukherjee, M.D., provides expert commentary on bioresorbable stents, an alternative to the traditional stents used in patients with cardiac conditions.

A simple fix to avoid some unnecessary coronary stents
Physician researchers at Thomas Jefferson University suspect that some cases of coronary artery spasm go unrecognized and are incorrectly treated with stents.

For malignant biliary obstruction, plastic stents may be cost-effective alternative
Preoperative biliary drainage (PBD) with stent placement has been commonly used for patients with malignant biliary obstruction.

3-D printing customized vascular stents
Using high-resolution 3-D printing, Northwestern University researchers can create flexible, biodegradable stents on-demand that are customized for a patient's specific anatomy.

Read More: Stents News and Stents Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.