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

Ling Li; Zhi Cheng Yao; Alyssa Parian; Yueh Hsun Yang; Jeffrey Chao; Jason Yin; Kevan J. Salimian; Sashank K. Reddy; Atif Zaheer; Susan L. Gearhart; Hai Quan Mao; Florin M. Selaru

doi:10.1126/sciadv.ade1067

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

Ling Li, Zhi Cheng Yao, Alyssa Parian, Yueh Hsun Yang, Jeffrey Chao, Jason Yin, Kevan J. Salimian, Sashank K. Reddy, Atif Zaheer, Susan L. Gearhart, Hai Quan Mao, Florin M. Selaru

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	eade1067
Journal	Science Advances
Volume	9
Issue number	1
DOIs	https://doi.org/10.1126/sciadv.ade1067
State	Published - Jan 2023

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@article{7ea0908c4be44dcc96638389c4467ad1,

title = "A nanofiber-hydrogel composite improves tissue repair in a rat model of Crohn{\textquoteright}s disease perianal fistulas",

abstract = "Perianal fistulas (PAFs) represent a severe complication of Crohn{\textquoteright}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.",

author = "Ling Li and Yao, {Zhi Cheng} and Alyssa Parian and Yang, {Yueh Hsun} and Jeffrey Chao and Jason Yin and Salimian, {Kevan J.} and Reddy, {Sashank K.} and Atif Zaheer and Gearhart, {Susan L.} and Mao, {Hai Quan} and Selaru, {Florin M.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved.",

year = "2023",

month = jan,

doi = "10.1126/sciadv.ade1067",

language = "English (US)",

volume = "9",

journal = "Science Advances",

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AU - Li, Ling

AU - Yao, Zhi Cheng

AU - Parian, Alyssa

AU - Yang, Yueh Hsun

AU - Chao, Jeffrey

AU - Yin, Jason

AU - Salimian, Kevan J.

AU - Reddy, Sashank K.

AU - Zaheer, Atif

AU - Gearhart, Susan L.

AU - Mao, Hai Quan

AU - Selaru, Florin M.

PY - 2023/1

Y1 - 2023/1

N2 - 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.

AB - 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.

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

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