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Surgical adhesions are a prevalent complication resulting from open or laparoscopic abdominal procedures, and they can sometimes lead to severe health issues. Recent research indicates that a gel enriched with T-5224, a molecule that disrupts the signaling pathway related to scar tissue formation, can significantly prevent these adhesions in animal models such as mice and pigs.
This innovative gel, which can be administered as a spray or wash immediately following surgery, releases T-5224 over two weeks. This small molecule effectively inhibits the activation of fibroblasts—cells responsible for the formation of adhesions—while not interfering with normal healing processes.
The potential of this approach is profound. If applicable to human patients, it could not only alleviate suffering by reducing occurrences of chronic pain, infertility, and bowel obstructions caused by severe adhesions but could also lead to substantial healthcare savings. Enhancing surgical outcomes and reducing complications could save billions annually, according to the researchers involved. Demonstrating effectiveness in larger animals represents an important milestone toward initiating clinical trials in humans.
Professor Michael Longaker, MD, a prominent figure in this study, explains, “Adhesions primarily occur when surgical intervention impacts the bowel, regardless of whether the procedure is open or minimally invasive. Our gel significantly lowers the risk of developing adhesions while maintaining the body’s natural healing capabilities. Incorporating this into surgical routines would be straightforward for surgeons, as they already perform washouts at the end of procedures.”
Michael Longaker and assistant professor Daniel Delitto, MD, PhD, led the research published on March 12 in Science Translational Medicine. The study’s lead authors include former postdoctoral scholar Deshka Foster, MD, PhD, along with postdoctoral scholar Jason Guo, PhD.
Understanding the Impact of Scar Tissue
Abdominal adhesions can develop during the healing process, with studies indicating that between 50% and 90% of abdominal surgeries result in some adhesion formation, depending on surgery type and location. These adhesions can create a network of excessive scar tissue that adheres organs or tissues to one another or to the abdominal wall.
While many adhesions may remain asymptomatic, around 5% to 20% can lead to significant complications, including chronic pain, infertility, and potentially life-threatening bowel obstructions. Currently, reliable preventive measures or treatments for these fibrous connections are lacking, which results in substantial economic costs to the healthcare system each year.
The research team has extensively studied scar tissue formation and adhesion processes over the years. In a 2020 study, they pinpointed the biological pathway involved in adhesion development in both mice and humans. Their findings revealed that inhibiting the c-Jun protein—which is activated in fibroblasts during injury—markedly decreased adhesion formation in controlled experiments with mice.
T-5224, the molecule in the gel, has previously shown promise in mitigating excessive scarring and inflammation in conditions like rheumatoid arthritis and in animal studies focused on cancer and inflammation.
“We sought to determine if we could effectively deliver this small molecule directly to the abdominal cavity over several days and whether it would impact adhesion development,” Longaker noted.
Through collaboration with materials science and engineering associate professor Eric Appel, PhD, the researchers created a shear-thinning hydrogel capable of traveling fluidly under pressure (such as when injected with a syringe) and solidifying when the pressure is released. This gel, once infused with T-5224, allows for a gradual release of the molecule over a two-week period post-surgery.
In tests with mice and minipigs, the T-5224-infused gel demonstrated a remarkable nearly 300% decrease in adhesion formation compared to groups receiving only saline or the gel without T-5224.
“The sustained release properties of the T-5224 hydrogel, coupled with its ease of application, present significant advantages for developing a potential clinical treatment for adhesions,” said Foster. “We are excited to pursue the next steps necessary to transition this solution toward clinical use.”
Longaker emphasized the dual significance of their findings. “While it is exciting to discover a method to block adhesions, the reassurance that we observed no negative effects on wound healing is crucial. If our approach interfered with the healing process, it would not be viable. The data we have collected in a large animal context indicates that this treatment is both safe and effective, opening the door for discussions about human trials.”
The study received funding from various esteemed organizations, including the National Institutes of Health and the National Science Foundation, among others. Furthermore, Longaker, Foster, and their colleagues hold patents related to this innovative use of T-5224 in hydrogels, while Appel has interests in a company related to the technology developed.
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