Researchers Develop Nanofiber Hydrogel to Improve Outcomes for Patients with Perianal Fistulas
An all-Johns Hopkins team seeks new way to help patients avoid high recurrence of the condition.
As researchers across academic medicine pursue better therapies for patients with perianal fistulas, experts at Johns Hopkins test a nanofiber gel to hold stem cells at the site of treatment. Image: 3D representation of nanofibers. Source: Getty Images
Johns Hopkins gastroenterologist Florin M. Selaru is looking for a more effective method to treat perianal fistulas than current methodologies, including surgery. In 2023, he led a group that published an article in the journal Science Advances showing a potentially groundbreaking treatment for the condition.
“Right now, there are not a lot of reliably effective treatments,” says Selaru.
Selaru and his team have developed a nanofiber hydrogel that — in rat models of Crohn’s disease-related perianal fistulas — improved tissue repair and reduced recurrence. Along with surgery, this local treatment is applied directly into the fistula tract.
The team of Johns Hopkins researchers, which includes biomedical engineers, surgeons, pathologists, public health experts, radiologists and oncologists — engineered the hydrogel to keep the stem cells in the affected area longer than is now possible. In their journal article, they write that the gel is stiff, helping it remain fixed in place to promote better healing.
In 2020, approximately 2.5 million Americans lived with Crohn’s disease, an autoimmune disease that causes inflammation in the digestive tract. The number of Americans with the disease is projected to jump to 3.5 million by 2030, and today, between 30% and 40% of patients with Crohn’s experience perianal fistulas, often leading to incontinence and other complications.
“An ideal treatment would surgically close the internal orifice of the fistula, so we can interrupt the contamination with stool and bacteria. Then, we’d use the gel containing stem cells to fill the space caused by the fistula.”
Florin Selaru
Selaru says there are several reasons that perianal fistulas are difficult to treat.
“First, they arise in an inflammatory milieu, both in the rectum and within the fistula tract itself,” he says. “That makes the inflammation hard to clear. The overall efficacy of current treatments is generally less than 50%.”
Because perianal fistulas connect to the rectum, it’s common for stool to fill the tunnel, making healing even more difficult. Surgical closure of the fistula tract is the current standard.
“But more often than not, it comes back,” says Selaru. “We believe that the inflammatory process that caused the fistula is likely the factor that brings it back so often.”
Stem cells collected from the patient’s own fat tissue can reduce the inflammation and provide regeneration signals. The current method of injecting the fat tissue-derived stem cells is not effective because these cells tend to migrate away quickly; therefore, they do not provide sufficient treatment benefit.
Finally, because the fistulas develop in muscle-rich tissue, any material used to treat the condition has to be stiff enough to remain in place long enough to be of some help to the patient.
“An ideal treatment would surgically close the internal orifice of the fistula, so we can interrupt the contamination with stool and bacteria,” says Selaru. “Then, we’d use the gel containing stem cells to fill the space caused by the fistula.”
“The nanofiber hydrogel is designed to be sufficiently stiff to anchor in the fistula track, and more importantly, it helps to better retain these fat tissue-derived stem cells at the site of injury, and thereby increase treatment efficacy,” says Hai-Quan Mao, director of the Johns Hopkins Institute for NanoBioTechnology and a collaborator on the hydrogel project.
Selaru says he and his team are working on the next phases of the research, which include further refinement and new ways to combine therapies.
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