Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair

Abstract Protein self‐assembly allows for the formation of diverse supramolecular materials from relatively simple building blocks. In this study, a single‐component self‐assembling hydrogel is developed using the recombinant protein CsgA, and its successful application for spinal cord injury repair...

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Main Authors: Yi Wei, Xiaolin Zhou, Zhenhua Li, Qing Liu, Han Ding, Yunlong Zhou, Ruo‐feng Yin, Lifei Zheng
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202405054
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author Yi Wei
Xiaolin Zhou
Zhenhua Li
Qing Liu
Han Ding
Yunlong Zhou
Ruo‐feng Yin
Lifei Zheng
author_facet Yi Wei
Xiaolin Zhou
Zhenhua Li
Qing Liu
Han Ding
Yunlong Zhou
Ruo‐feng Yin
Lifei Zheng
author_sort Yi Wei
collection DOAJ
description Abstract Protein self‐assembly allows for the formation of diverse supramolecular materials from relatively simple building blocks. In this study, a single‐component self‐assembling hydrogel is developed using the recombinant protein CsgA, and its successful application for spinal cord injury repair is demonstrated. Gelation is achieved by the physical entanglement of CsgA nanofibrils, resulting in a self‐supporting hydrogel at low concentrations (≥5 mg mL−1). By leveraging the programmability of the CsgA gene sequence, the bioactive hydrogel is enhanced by fusing functional peptide GHK. GHK is recognized for its anti‐inflammatory, antioxidant, and neurotrophic factor‐stimulating properties, making it a valuable addition to the hydrogel for spinal cord injury repair applications. In vitro experiments demonstrate that the CsgA‐GHK hydrogel can modulate microglial M2 polarization, promote neuronal differentiation of neural stem cells, and inhibit astrocyte differentiation. Additionally, the hydrogel shows efficacy in alleviating inflammation and promotes neuronal regeneration at the injury site, leading to significant functional recovery in a rat model with compression injury spinal cord cavity. These findings lay the groundwork for developing a modular design platform for recombinant CsgA protein hydrogels in tissue repair applications.
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spelling doaj-art-c158f1e957ea4d9b97ff14aafd99ca542025-08-20T02:23:12ZengWileyAdvanced Science2198-38442025-03-011210n/an/a10.1002/advs.202405054Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury RepairYi Wei0Xiaolin Zhou1Zhenhua Li2Qing Liu3Han Ding4Yunlong Zhou5Ruo‐feng Yin6Lifei Zheng7Wenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325001 ChinaChina‐Japan Union Hospital Jilin University Changchun Jilin 130031 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325001 ChinaAbstract Protein self‐assembly allows for the formation of diverse supramolecular materials from relatively simple building blocks. In this study, a single‐component self‐assembling hydrogel is developed using the recombinant protein CsgA, and its successful application for spinal cord injury repair is demonstrated. Gelation is achieved by the physical entanglement of CsgA nanofibrils, resulting in a self‐supporting hydrogel at low concentrations (≥5 mg mL−1). By leveraging the programmability of the CsgA gene sequence, the bioactive hydrogel is enhanced by fusing functional peptide GHK. GHK is recognized for its anti‐inflammatory, antioxidant, and neurotrophic factor‐stimulating properties, making it a valuable addition to the hydrogel for spinal cord injury repair applications. In vitro experiments demonstrate that the CsgA‐GHK hydrogel can modulate microglial M2 polarization, promote neuronal differentiation of neural stem cells, and inhibit astrocyte differentiation. Additionally, the hydrogel shows efficacy in alleviating inflammation and promotes neuronal regeneration at the injury site, leading to significant functional recovery in a rat model with compression injury spinal cord cavity. These findings lay the groundwork for developing a modular design platform for recombinant CsgA protein hydrogels in tissue repair applications.https://doi.org/10.1002/advs.202405054CsgAhydrogelrecombinant proteinself‐assemblyspinal cord injury repair
spellingShingle Yi Wei
Xiaolin Zhou
Zhenhua Li
Qing Liu
Han Ding
Yunlong Zhou
Ruo‐feng Yin
Lifei Zheng
Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair
Advanced Science
CsgA
hydrogel
recombinant protein
self‐assembly
spinal cord injury repair
title Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair
title_full Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair
title_fullStr Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair
title_full_unstemmed Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair
title_short Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair
title_sort genetically programmed single component protein hydrogel for spinal cord injury repair
topic CsgA
hydrogel
recombinant protein
self‐assembly
spinal cord injury repair
url https://doi.org/10.1002/advs.202405054
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AT yunlongzhou geneticallyprogrammedsinglecomponentproteinhydrogelforspinalcordinjuryrepair
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