[Photo by Piron Guillaume on Unsplash]
Abdominal adhesions occur when excessive scar tissue forms — often after open surgery — causing organs and tissues to tether to one another or the abdominal wall. They can occasionally cause a more serious complication, such as a small bowel obstruction.
The Stanford researchers envision their hydrogel applied as a spray or wash to the inside of the abdominal cavity immediately after surgery. Over two weeks, it releases a small molecule, T-5224, that can block the activation of adhesion-forming cells called fibroblasts without affecting normal wound healing.
The gel could provide a practical, simple way to prevent or reduce the formation of post-surgical abdominal adhesions in humans, according to the research team.
“As a surgeon, I’m already used to washing out the surgical site at the end of the procedure, so this would be easy to incorporate into our normal workflow,” Dr. Michael Longaker said in a post on the university’s website. Longaker is a professor of surgery at Stanford who was a senior author of the research team’s paper along with Dr. Daniel Delitto.
Former postdoctoral scholar and surgical resident Dr. Deshka Foster and postdoctoral scholar Jason Guo are the lead authors of the research, published March 12 in Science Translational Medicine.
Longaker, Foster and their colleagues back in 2020 identified the biological pathway responsible for adhesion formation in mice and humans and showed that inhibiting the activity of a protein called c-Jun — produced by fibroblasts in response to injury — could reduce the formation of adhesions in laboratory mice. An inhibitory molecule called T-5224 could modulate the excessive scarring and inflammation.
“We wanted to learn whether we could deliver this small molecule inhibitor directly to the abdominal cavity over a period of several days and, if so, whether it would impact adhesion formation,” Longaker said.
Study co-author Eric Appel, an associate professor of materials science and engineering, worked with the research team to design a biomaterial called a shear-thinning hydrogel that flows like a liquid under pressure — such as being forced through a syringe –— but stabilizes when the force is removed. Impregnated with T-5224, the gel could slowly release the small molecule over 14 days.
When tested in mice and minipigs, the T-5224-impregnated gel significantly reduced the formation of adhesions — scored from 0 to 5 by the degree of contact between neighboring tissues – by nearly 300% in response to abdominal surgery compared with animals that received a saline wash of the surgical site or application of the gel without T-5224.
“The sustained release formulation of T-5224-hydrogel and the ability to easily apply it to the abdominal cavity are ideal qualities for a potential clinical therapy for adhesions,” Foster said. “We are eager to take the next steps to bring this approach into the clinic.”
