A nanofiber-hydrogel composite improves tissue repair in a rat model of Crohn’s disease perianal fistulas

Author:

Li Ling1ORCID,Yao Zhi-Cheng234ORCID,Parian Alyssa1,Yang Yueh-Hsun245ORCID,Chao Jeffrey246ORCID,Yin Jason234,Salimian Kevan J.7,Reddy Sashank K.25ORCID,Zaheer Atif8ORCID,Gearhart Susan L.9ORCID,Mao Hai-Quan23410ORCID,Selaru Florin M.111ORCID

Affiliation:

1. Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

2. Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.

3. Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.

4. Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

5. Department of Plastic and Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.

6. Department of Public Health Studies, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.

7. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

8. Division of Radiology and Radiological Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

9. Division of Colorectal Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

10. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

11. Department of Oncology, Sidney Kimmel Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Abstract

Perianal fistulas (PAFs) represent a severe complication of Crohn’s disease (CD). Despite the advent of biologic and small-molecule therapeutics for luminal disease, PAFs in CD (CD-PAF) are relatively resistant to treatment, with less than 50% responding to any therapy. We report an injectable, biodegradable, mechanically fragmented nanofiber-hydrogel composite (mfNHC) loaded with adipose-derived stem cells (ADSCs) for the treatment of fistulas in a rat model of CD-PAF. The ADSC-loaded mfNHC results in a higher degree of healing when compared to surgical treatment of fistulas, which is a standard treatment. The volume of fistulas treated with mfNHC is decreased sixfold compared to the surgical treatment control. Molecular studies reveal that utilization of mfNHC reduced local inflammation and improved tissue regeneration. This study demonstrates that ADSC-loaded mfNHC is a promising therapy for CD-PAF, and warrants further studies to advance mfNHC toward clinical translation.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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