Postoperative adhesions are abrogated by a sustained-release anti-JUN therapeutic in preclinical models.

Anyone who has had abdominal surgery is at risk of developing internal scar tissue called adhesions — bands of fibrous tissue that can form between organs and abdominal structures as they heal. Adhesions are surprisingly common, occurring after roughly half to nearly all abdominal operations, and they're the leading cause of bowel obstructions. They can also cause chronic pain and, in some cases, infertility. Despite how widespread this problem is, there's currently no proven way to prevent or treat adhesions once they form. Adhesions mainly develop from the peritoneum, the thin membrane lining the abdominal organs and cavity, and they're built from fibroblasts, a type of connective tissue cell that multiplies at the injury site during healing. In earlier research, the same team discovered that a molecular signaling pathway involving a protein called JUN plays a key role in driving this scarring process, and that a drug called T-5224, which blocks JUN activity, could reduce adhesion formation. Building on that discovery, this study aimed to turn that finding into something more practical for actual surgical use. The researchers embedded the JUN-blocking drug into a specially designed hydrogel — a soft, gel-like material with anti-adhesion properties of its own — engineered to be injected into the abdominal cavity after surgery. This gel is a type known as "shear-thinning," meaning it flows easily when injected through a syringe or surgical instrument but then settles back into a stable gel once in place, allowing it to coat tissues and slowly release the JUN-blocking drug over time. Its consistency also makes it compatible with both traditional open surgery and minimally invasive, laparoscopic techniques. The researchers tested this drug-loaded gel first in mice and then in pigs, whose abdominal anatomy and healing processes more closely resemble those of humans. Across both animal models, the treatment proved to be safe and well tolerated, with no concerning side effects. Importantly, it also worked: animals treated with the gel developed noticeably fewer adhesions, and the adhesions that did form showed less scarring damage when examined at a very detailed, microscopic level. To move closer to eventual use in real patients, the researchers developed a large-animal model in pigs that more closely mimicked an actual surgical scenario, involving a segment of the bowel being surgically removed and reconnected — a common procedure where adhesions are a particular concern. Detailed genetic analysis of individual cells confirmed that the JUN signaling pathway was indeed suppressed in the scar-forming cells of animals treated with the drug-loaded gel. Encouragingly, the treatment prevented adhesions effectively without interfering with proper healing of the surgical bowel connection or the abdominal wall itself. Because the biological process behind adhesion formation appears to be similar across different areas of the body, this treatment approach could potentially be useful for a wide range of surgical procedures, not just the specific one tested here. Given how common and burdensome this surgical complication is, developing an effective and practical way to prevent it could have a substantial positive impact on patient recovery and long-term quality of life.