Injectable hydrogel composite loaded with stem cells shows success in treating perianal fistulas

In a new study using a rat model of Crohn’s disease, a biodegradable hydrogel composite loaded with stem cells developed by Johns Hopkins Medicine researchers, in collaboration with the Whiting School of Engineering, has shown significant success in the treatment of perianal fistulas. (PAF) – one of many complications of Crohn’s disease.

Crohn’s disease, a subtype of inflammatory bowel disease, is a condition that affects more than three million adult Americans, according to the U.S. Centers for Disease Control and Prevention. About 30 to 40 percent of Crohn’s disease patients develop perianal fistulas — an inflamed tunnel between the skin and the lining of the anus. Fistulas can lead to pain, swelling, discomfort, and leakage of blood or pus. Surgery is usually needed to treat the condition. However, more than half of patients do not benefit from currently available treatments.

The injectable, biodegradable, mechanically fragmented nanofiber hydrogel composite (mfNHC), loaded with stem cells, that the Johns Hopkins team designed can be injected into the fistula tract and showed a higher rate of healing, reducing the size of fistulas six-fold. compared to surgery.

The results were published on January 4 in Scientific progress.

A large number of patients are diagnosed with Crohn’s disease in their late teens to early 20s, and they consider living with perianal fistulas for a lifetime. This condition in patients with Crohn’s disease is notoriously difficult to treat. We hope that these results provide a potential new treatment paradigm to be translated and improve the quality of life for these patients.”

Florin M. Selaru, MD, associate professor of medicine and oncology; director of the IBD Center at Hopkins and the Atran Professor of IBD Research at Johns Hopkins Medicine and one of the senior authors of the study

Selaru says previous studies and current clinical trials have shown that stem cell injection around fistula tracts helped with local healing. However, it is unlikely that the stem cells will be retained around the fistula spur for a meaningful length of time that will allow for any significant healing. The hydrogel created by the team can be injected directly into the fistula tract. It’s infused with nanofiber fragments that give the substance enough stiffness to anchor the stem cells in place at the site of the fistula, so they don’t pull away. This will aid in tissue regeneration and promote healthy healing.

“Think of it as a local delivery of a tissue regeneration nanogel-nanofiber composite that also keeps the stem cells at the site of injury and enables healing,” says Selaru. The gel built a scaffold that trapped the stem cells at the site of the fistulas and promoted regenerative healing. The results showed that the gel had an overall reduction in the volume of the fistula tract by six times, compared to surgery.

“These results are very exciting for the future of biostimulation tissue repair for chronic injuries – even beyond PAF,” said Hai-Quan Mao, Ph.D., a professor in the Whiting School of Engineering’s Department of Materials Science and Engineering and Department of Biomedical Engineering, and another senior author of this study. Mao is also director of the Johns Hopkins Institute for NanoBioTechnology.

However, Selaru warns that these very encouraging results need to be verified in human trials. The experiments performed so far have laid the foundations for such translational future studies. The team plans to continue this work and improve the gel, including exploring the idea of ​​a foam version.

Other researchers include Ling Li, Zhi-Cheng Yao, Alyssa Parian, Yueh-Hsun Yang, Jeffrey Chao, Jason Yin, Kevan Salimian, Sashank Reddy, Atif Zaheer, and Susan Gearhart.

Funding for this work was supported by The Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health, and the Atran Foundation.


Magazine reference:

Li, L., et al. (2023) A nanofiber-hydrogel composite improves tissue repair in a rat model of Crohn’s disease perianal fistula. Scientific progress.