"Smart" Sutures Could Aid Drug Delivery and Surgical Healing
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A team of engineers from the Massachusetts Institute of Technology (MIT) has developed “smart” sutures with the potential to benefit Crohn’s disease patients undergoing surgery, and could also have applications for sensing inflammation, drug delivery and cell therapies. The research is published in Matter.
Creating advanced sutures
Thousands of years ago, the Romans developed “catgut” sutures made from the twisted intestines of plant-eating animals. They are designed to be gradually dissolved by the body within around 90 days, avoiding the need for removal.
Interestingly, catgut sutures have never had anything to do with cats. Modern catgut sutures are produced from purified collagen – a major component of connective tissue – derived from cows, sheep or goats.
Now, researchers from MIT set out to improve upon these sutures and give them an innovative twist, developing a suture that could be both tough and absorbable but also possess advanced features such as sensing inflammation and delivering drugs.
Their focus was developing an advanced suture that would improve outcomes for surgery for Crohn’s disease, an inflammatory bowel condition. Some patients need surgery to remove part of their damaged intestine, which involves suturing the two remaining ends of the intestine together. Should these fail, this can have devastating results for the patient.
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The MIT researchers developed a suture that could effectively hold the tissue in place and detect inflammation, an indicator that the intestines are not healing as they should.
Applications for inflammation, drug delivery and cell therapy
The researchers developed the new sutures from a cell-free material they call “De-gut”, made from treated and “decellularized” pig tissue. Detergents remove the pig cells from the tissue, leaving behind the De-gut material formed from collagen and other biomolecules that form the tissue’s extracellular matrix. This decreases the risk of causing inflammation when used in patients.
The material was dried and twisted into strands to form the new sutures. Experiments measuring their tensile strength – the amount of stretch they can withstand before breaking – showed they had comparable strength to current standard catgut sutures.
Having demonstrated the sutures’ strength, the researchers next aimed to give them their advanced functions and add a hydrogel coating capable of carrying various types of cargo. Microparticles embedded within the hydrogel can serve various functions, such as sensing inflammation, delivering drug molecules and carrying living cells.
To act as a sensor, microparticles in the hydrogel were coated with peptides that are released in the presence of matrix metalloproteinases (MMPs), enzymes associated with inflammation. The released peptides can then be detected in urine to suggest inflammation at the suture site.
For drug delivery, the hydrogel was coated with the steroid drug dexamethasone and the monoclonal antibody drug adalimumab, which are both used for inflammatory bowel disease. Microparticles made from FDA-approved polymers – such as PLGA and PLA – ensured that the drugs were released at a controlled rate.
Alongside drug therapies, these smart sutures may also be used to deliver cellular therapies, including stem cells. The researchers embedded the sutures with stem cells tagged with a fluorescent marker, and studies in mice confirmed that these stem cells remained viable for at least seven days and were capable of producing growth factors.
“Decellularized tissues have been extensively used in regenerative medicine with their superb biofunctionality,” said Dr. Jung Seung Lee, co-lead author of the paper. “We now suggest a novel platform for performing sensing and delivery using decellularized tissue, which will open up new applications of tissue-derived materials.”
The future of “smart” sutures
“What we have is a suture that is bioderived and modified with a hydrogel coating capable of being a reservoir for sensors for inflammation, or for drugs such as monoclonal antibodies to treat inflammation. Remarkably, the coating also has the capacity to retain cells that are viable for a prolonged period,” said Dr. Giovanni Traverso, associate professor of mechanical engineering at MIT and the senior author of the study.
Now, the team is working on testing these promising applications in more detail and on scaling up the manufacturing process for the sutures. The authors also note that this approach has the potential to be adapted to deliver other kinds of drugs, including antibiotics or chemotherapy. In future studies, they hope to investigate using these sutures in other regions of the body, not just the gastrointestinal tract.
Reference: Lee JS, Kim H, Carroll G, et al. A multifunctional decellularized gut suture platform. Matter. 2023;0(0). doi: 10.1016/j.matt.2023.04.015
This article is a rework of a press release issued by Massachusetts Institute of Technology. Material has been edited for length and content.