Sutureless neurorrhaphy system using a macrophage-polarizing in situ visible light-crosslinkable adhesive protein hydrogel for functional nerve regeneration

Hogyun Cheong; Young Joon Jun; Eun Young Jeon; Jong In Lee; Hyun Jun Jo; Hae Yeon Park; Eunjin Kim; Jong Won Rhie; Kye Il Joo; Hyung Joon Cha

doi:10.1016/j.cej.2022.136641

Sutureless neurorrhaphy system using a macrophage-polarizing in situ visible light-crosslinkable adhesive protein hydrogel for functional nerve regeneration

Hogyun Cheong, Young Joon Jun, Eun Young Jeon, Jong In Lee, Hyun Jun Jo, Hae Yeon Park, Eunjin Kim, Jong Won Rhie, Kye Il Joo, Hyung Joon Cha

Department of Chemical Engineering & Materials Science

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

10 Scopus citations

Abstract

Surgical intervention after traumatic peripheral nerve injury relies heavily on sutures. While the suture method often burdens functional nerve regeneration by causing secondary traumatic damage and eliciting prolonged inflammatory immune responses, replacing sutures has rarely been considered because secure anastomosis between severed nerve ends has been the utmost priority in neurorrhaphy. In the present work, a macrophage-polarizing sutureless neurorrhaphy system was proposed by using an in situ visible light-crosslinkable protein-based bioadhesive hydrogel containing a functional neurotransmitter peptide. The efficacy of the proposed bioadhesive hydrogel as a successful sutureless neurorrhaphy system was intensively evaluated in vitro and in vivo. Using a rat sciatic nerve defect model, our findings suggested that this macrophage-polarizing bioadhesive hydrogel offered effective sutureless anastomosis and the capability to induce M₂ macrophage polarization for effective tissue remodeling, significantly enhancing functional nerve regeneration compared with conventional sutures. Taken together, these results suggest that our macrophage-polarizing functional bioadhesive hydrogel system can be utilized as a promising alternative to surgical sutures for nerve regenerative medicine applications.

Original language	English
Article number	136641
Journal	Chemical Engineering Journal
Volume	445
DOIs	https://doi.org/10.1016/j.cej.2022.136641
State	Published - 1 Oct 2022

Bibliographical note

Funding Information:
We acknowledge the financial support by the Korea Health Technology R&D Project (grant number: HI20C0090) through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Korea (to H.J. Cha & K.I. Joo) and the Marine Biotechnology Program through the Korea Institute of Marine Science & Technology Promotion funded by the Ministry of Oceans and Fisheries, Korea (to H.J. Cha, K.I. Joo & J.W. Rhie). We also thank Nature Gluetech, Inc. for providing the bioengineered MAP.

Funding Information:
We acknowledge the financial support by the Korea Health Technology R&D Project (grant number: HI20C0090) through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Korea (to H.J. Cha & K.I. Joo) and the Marine Biotechnology Program through the Korea Institute of Marine Science & Technology Promotion funded by the Ministry of Oceans and Fisheries, Korea (to H.J. Cha, K.I. Joo & J.W. Rhie). We also thank Nature Gluetech, Inc. for providing the bioengineered MAP. The data that support this study are available within the article and its Supplementary data files or available from the authors upon request.

Publisher Copyright:
© 2022 Elsevier B.V.

Keywords

Functional nerve regeneration
M macrophage polarization
Mussel adhesive protein
Substance P
Sutureless neurorrhaphy
Visible light-induced crosslinking bioadhesive hydrogel

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10.1016/j.cej.2022.136641

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Cheong, H., Jun, Y. J., Jeon, E. Y., Lee, J. I., Jo, H. J., Park, H. Y., Kim, E., Rhie, J. W., Joo, K. I., & Cha, H. J. (2022). Sutureless neurorrhaphy system using a macrophage-polarizing in situ visible light-crosslinkable adhesive protein hydrogel for functional nerve regeneration. Chemical Engineering Journal, 445, Article 136641. https://doi.org/10.1016/j.cej.2022.136641

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title = "Sutureless neurorrhaphy system using a macrophage-polarizing in situ visible light-crosslinkable adhesive protein hydrogel for functional nerve regeneration",

abstract = "Surgical intervention after traumatic peripheral nerve injury relies heavily on sutures. While the suture method often burdens functional nerve regeneration by causing secondary traumatic damage and eliciting prolonged inflammatory immune responses, replacing sutures has rarely been considered because secure anastomosis between severed nerve ends has been the utmost priority in neurorrhaphy. In the present work, a macrophage-polarizing sutureless neurorrhaphy system was proposed by using an in situ visible light-crosslinkable protein-based bioadhesive hydrogel containing a functional neurotransmitter peptide. The efficacy of the proposed bioadhesive hydrogel as a successful sutureless neurorrhaphy system was intensively evaluated in vitro and in vivo. Using a rat sciatic nerve defect model, our findings suggested that this macrophage-polarizing bioadhesive hydrogel offered effective sutureless anastomosis and the capability to induce M2 macrophage polarization for effective tissue remodeling, significantly enhancing functional nerve regeneration compared with conventional sutures. Taken together, these results suggest that our macrophage-polarizing functional bioadhesive hydrogel system can be utilized as a promising alternative to surgical sutures for nerve regenerative medicine applications.",

keywords = "Functional nerve regeneration, M macrophage polarization, Mussel adhesive protein, Substance P, Sutureless neurorrhaphy, Visible light-induced crosslinking bioadhesive hydrogel",

author = "Hogyun Cheong and Jun, {Young Joon} and Jeon, {Eun Young} and Lee, {Jong In} and Jo, {Hyun Jun} and Park, {Hae Yeon} and Eunjin Kim and Rhie, {Jong Won} and Joo, {Kye Il} and Cha, {Hyung Joon}",

note = "Funding Information: We acknowledge the financial support by the Korea Health Technology R&D Project (grant number: HI20C0090) through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Korea (to H.J. Cha & K.I. Joo) and the Marine Biotechnology Program through the Korea Institute of Marine Science & Technology Promotion funded by the Ministry of Oceans and Fisheries, Korea (to H.J. Cha, K.I. Joo & J.W. Rhie). We also thank Nature Gluetech, Inc. for providing the bioengineered MAP. Funding Information: We acknowledge the financial support by the Korea Health Technology R&D Project (grant number: HI20C0090) through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Korea (to H.J. Cha & K.I. Joo) and the Marine Biotechnology Program through the Korea Institute of Marine Science & Technology Promotion funded by the Ministry of Oceans and Fisheries, Korea (to H.J. Cha, K.I. Joo & J.W. Rhie). We also thank Nature Gluetech, Inc. for providing the bioengineered MAP. The data that support this study are available within the article and its Supplementary data files or available from the authors upon request. Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

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AU - Park, Hae Yeon

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AU - Rhie, Jong Won

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AU - Cha, Hyung Joon

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N2 - Surgical intervention after traumatic peripheral nerve injury relies heavily on sutures. While the suture method often burdens functional nerve regeneration by causing secondary traumatic damage and eliciting prolonged inflammatory immune responses, replacing sutures has rarely been considered because secure anastomosis between severed nerve ends has been the utmost priority in neurorrhaphy. In the present work, a macrophage-polarizing sutureless neurorrhaphy system was proposed by using an in situ visible light-crosslinkable protein-based bioadhesive hydrogel containing a functional neurotransmitter peptide. The efficacy of the proposed bioadhesive hydrogel as a successful sutureless neurorrhaphy system was intensively evaluated in vitro and in vivo. Using a rat sciatic nerve defect model, our findings suggested that this macrophage-polarizing bioadhesive hydrogel offered effective sutureless anastomosis and the capability to induce M2 macrophage polarization for effective tissue remodeling, significantly enhancing functional nerve regeneration compared with conventional sutures. Taken together, these results suggest that our macrophage-polarizing functional bioadhesive hydrogel system can be utilized as a promising alternative to surgical sutures for nerve regenerative medicine applications.

AB - Surgical intervention after traumatic peripheral nerve injury relies heavily on sutures. While the suture method often burdens functional nerve regeneration by causing secondary traumatic damage and eliciting prolonged inflammatory immune responses, replacing sutures has rarely been considered because secure anastomosis between severed nerve ends has been the utmost priority in neurorrhaphy. In the present work, a macrophage-polarizing sutureless neurorrhaphy system was proposed by using an in situ visible light-crosslinkable protein-based bioadhesive hydrogel containing a functional neurotransmitter peptide. The efficacy of the proposed bioadhesive hydrogel as a successful sutureless neurorrhaphy system was intensively evaluated in vitro and in vivo. Using a rat sciatic nerve defect model, our findings suggested that this macrophage-polarizing bioadhesive hydrogel offered effective sutureless anastomosis and the capability to induce M2 macrophage polarization for effective tissue remodeling, significantly enhancing functional nerve regeneration compared with conventional sutures. Taken together, these results suggest that our macrophage-polarizing functional bioadhesive hydrogel system can be utilized as a promising alternative to surgical sutures for nerve regenerative medicine applications.

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Sutureless neurorrhaphy system using a macrophage-polarizing in situ visible light-crosslinkable adhesive protein hydrogel for functional nerve regeneration

Abstract

Bibliographical note

Keywords

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