Treating perianal fistulas with the injectable nanofiber-hydrogel composite loaded with stem cells. Image: Florin Selaru.In a study using a rat model of Crohn’s disease, a biodegradable hydrogel composite loaded with stem cells has shown significant success in treating perianal fistulas (PAF) – one of the many complications of Crohn’s disease. The novel hydrogel composite was developed by researchers at Johns Hopkins Medicine, in a collaborative effort with the Whiting School of Engineering at Johns Hopkins University.
Crohn’s disease, a subtype of inflammatory bowel disease, is a disorder estimated by the US Centers for Disease Control and Prevention to afflict more than three million adult Americans. Around 30–40% of patients with Crohn’s disease develop perianal fistulas — an inflamed tunnel between the skin and the inside 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, designed by the Johns Hopkins team, can be injected inside the fistula tract, and showed a high degree of healing, reducing the size of fistulas six-fold. The researchers report their results in a paper in Science Advances.
“A large number of patients are diagnosed with Crohn’s disease in their late teens to early 20s, and they are contemplating a lifetime of suffering from perianal fistulas,” says Florin Selaru, associate professor of medicine and oncology, director of the IBD Center at Hopkins and professor in IBD research at Johns Hopkins Medicine, and one of the senior authors of the paper. “This condition in Crohn’s patients is notoriously difficult to treat. We hope these results offer a potential new treatment paradigm to be translated and to improve the quality of life for these patients.”
Previous studies and current clinical trials have shown that stem cell injection around fistula tracts can help with local healing. However, the stem cells are unlikely to be retained around the fistula track for the length of time required for any significant healing. The novel hydrogel is designed to overcome this problem. It can be injected directly into the fistula tract, and is infused with nanofiber fragments that provide enough stiffness to anchor the stem cells in place at the site of the fistula, so they don’t migrate away. This will assist with 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 the injury and enables the healing to occur,” says Selaru. The gel builds a scaffold that retains the stem cells at the site of the fistulas and promotes regenerative healing. Results showed that the gel can help reduce the volume of fistulas by a factor of six.
“These results are very exciting for the future of bio-stimulation tissue repair for chronic injuries – even beyond PAF,” says Hai-Quan Mao, a professor in Whiting School of Engineering's Department of Materials Science and Engineering and Department of Biomedical Engineering, and another senior author of the paper. Mao is also director of the Johns Hopkins Institute for NanoBioTechnology.
Selaru cautions, however, that these very encouraging results need to be verified in human trials. The experiments conducted thus far have laid the foundation for such translational future studies. The team plans to continue this work and to improve the gel, including exploring the idea of a foam version.
This story is adapted from material from Johns Hopkins Medicine, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.