MIT engineers used kirigami-style etching to design a stent that may quickly lodge in tubular organs to launch medicine.
Inspired by kirigami, the Japanese artwork of folding and slicing paper to create three-dimensional buildings, MIT engineers and their collaborators have designed a brand new kind of stent that may very well be used to ship medicine to the gastrointestinal tract, respiratory tract, or different tubular organs in the physique.
The stents are coated in a clean layer of plastic etched with small “needles” that pop up when the tube is stretched, permitting the needles to penetrate tissue and ship a payload of drug-containing microparticles. These medicine are then launched over an prolonged time frame after the stent is eliminated.
This sort of localized drug supply may make it simpler to deal with inflammatory illnesses affecting the GI tract similar to inflammatory bowel illness or eosinophilic esophagitis, says Giovanni Traverso, an MIT assistant professor of mechanical engineering, a gastroenterologist at Brigham and Girls’s Hospital, and the senior creator of the examine.
“This expertise may very well be utilized in basically any tubular organ,” Traverso says. “Having the means to ship medicine regionally, on an rare foundation, actually maximizes the chance of serving to to resolve sufferers’ situations and may very well be transformative in how we take into consideration affected person care by enabling native, extended drug supply following a single remedy.”
Sahab Babaee, an MIT analysis scientist, is the lead creator of the paper, which was revealed on June 14, 2021, in Nature Supplies.
Inflammatory illnesses of the GI tract, similar to IBD, are sometimes handled with medicine that dampen the physique’s immune response. These medicine are normally injected, to allow them to have unwanted side effects elsewhere in the physique. Traverso and his colleagues needed to provide you with a means to ship such medicine immediately to the affected tissues, lowering the chance of unwanted side effects.
Stents may provide a means to ship medicine to a focused portion of the digestive tract, however inserting any type of stent into the GI tract could be difficult as a result of digested meals is repeatedly transferring by way of the tract. To make this risk extra possible, the MIT crew got here up with the thought of making a stent that might be inserted quickly, lodge firmly into the tissue to ship its payload, after which be simply eliminated.
The stent they designed has two key parts — a delicate, stretchy tube product of silicone-based rubber, and a plastic coating etched with needles that pop up when the tube is stretched. The design was impressed by kirigami, a way that Traverso’s lab has beforehand used to design a nonslip coating for shoe soles. Others have used it to create bandages that stick extra securely to knees and different joints.
“The novelty of our method is that we used instruments and ideas from mechanics, mixed with bioinspiration from scaly-skinned animals, to develop a brand new class of drug-releasing programs with the capability to deposit drug depots immediately into luminal partitions of tubular organs for prolonged launch,” Babaee says. “The kirigami stents have been engineered to present a reversible form transformation: from flat, to 3D, buckled-out needles for tissue engagement, after which to the unique flat form for simple and secure removing.”
On this examine, the MIT crew coated the plastic needles with microparticles that may carry medicine. After the stent is inserted endoscopically, the endoscope is used to inflate a balloon inside the tube, inflicting the tube to elongate. As the tube stretches, the pulling movement causes the needles in the plastic to pop up and launch their cargo.
“It’s a dynamic system the place you’ve got a flat floor, and you’ll create these little needles that pop up and drive into the tissue to do the drug supply,” Traverso says.
For this examine, the researchers created kirigami needles of a number of completely different configurations and dimensions. By various these options, in addition to the thickness of the plastic sheet, the researchers can management how deeply the needles penetrate into the tissue. “The benefit of our system is that it may be utilized to numerous size scales to be matched with the dimension of the goal tubular compartments of the gastrointestinal tract or any tubular organs,” Babaee says.
The researchers examined the stents by endoscopically inserting them into the esophagus of pigs. As soon as the stent was in place, the researchers inflated the balloon inside the stent, permitting the needles to pop up. The needles, which penetrated about half a millimeter into the tissue, have been coated with microparticles containing a drug known as budesonide, a steroid that’s used to deal with IBD and eosinophilic esophagitis.
As soon as the drug-containing particles have been deposited in the tissue, the researchers deflated the balloon, flattening out the needles so the stent may very well be endoscopically eliminated. This course of took solely a few minutes, and the microparticles then stayed in the tissue and regularly launched budesonide for about one week.
Relying on the composition of the particles, they may very well be tuned to launch medicine over a good longer time frame, Traverso says. This might make it simpler to maintain sufferers on the appropriate drug schedule, as a result of they might not want to take the drug themselves, however would periodically obtain their drugs by way of short-term insertion of the stent. It could additionally keep away from the unwanted side effects that may happen with systemic drug administration.
The researchers additionally confirmed that they might ship the stents into blood vessels and the respiratory tract. They’re now engaged on delivering different sorts of medicine and on scaling up the manufacturing course of, with the purpose of finally testing the stents in sufferers.
Reference: “Kirigami-inspired stents for sustained native supply of therapeutics” by Sahab Babaee, Yichao Shi, Saeed Abbasalizadeh, Siddartha Tamang, Kaitlyn Hess, Pleasure E. Collins, Keiko Ishida, Aaron Lopes, Michael Williams, Mazen Albaghdadi, Alison M. Hayward and Giovanni Traverso, 14 June 2021, Nature Supplies.
The analysis was funded by MIT’s Division of Mechanical Engineering. Different authors of the paper embrace Yichao Shi, Saeed Abbasalizadeh, Siddartha Tamang, Kaitlyn Hess, Pleasure Collins, Keiko Ishida, Aaron Lopes, Michael Williams, Mazen Albaghdadi, and Alison Hayward.