Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s disease

Abstract Background Parkinson’s disease (PD) is one of the most common long-term neurodegenerative diseases. Current treatments for PD are mostly based on surgery and medication because of the limitation and challenges in selecting proper biomaterials. In this study, an injectable bioactive hydrogel...

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Main Authors: Junpeng Xu, Tsai-Yu Chen, Chun-Hwei Tai, Shan-hui Hsu
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2023-02-01
Series:Biomaterials Research
Subjects:
Online Access:https://doi.org/10.1186/s40824-023-00347-0
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author Junpeng Xu
Tsai-Yu Chen
Chun-Hwei Tai
Shan-hui Hsu
author_facet Junpeng Xu
Tsai-Yu Chen
Chun-Hwei Tai
Shan-hui Hsu
author_sort Junpeng Xu
collection DOAJ
description Abstract Background Parkinson’s disease (PD) is one of the most common long-term neurodegenerative diseases. Current treatments for PD are mostly based on surgery and medication because of the limitation and challenges in selecting proper biomaterials. In this study, an injectable bioactive hydrogel based on novel tannic acid crosslinker was developed to treat PD. Methods The oxidized tannic acid modified gold nano-crosslinker was synthesized and used to effectively crosslink chitosan for preparation of the bioactive self-healing hydrogel. The crosslinking density, conductivity, self-healing ability, and injectability of the hydrogel were characterized. Abilities of the hydrogel to promote the proliferation and differentiation of neural stem cells (NSCs) were assessed in vitro. Anti-inflammatory property was analyzed on J774A.1 macrophages. The hydrogel was injected in the PD rat model for evaluation of the motor function recovery, electrophysiological performance improvement, and histological repair. Results The hydrogel exhibited self-healing property and 34G (~ 80 μm) needle injectability. NSCs grown in the hydrogel displayed long-term proliferation and differentiation toward neurons in vitro. Besides, the hydrogel owned strong anti-inflammatory and antioxidative capabilities to rescue inflamed NSCs (~ 90%). Brain injection of the bioactive hydrogel recovered the motor function of PD rats. Electrophysiological measurements showed evident alleviation of irregular discharge of nerve cells in the subthalamic nucleus of PD rats administered with the hydrogel. Histological examination confirmed that the hydrogel alone significantly increased the density of tyrosine hydroxylase positive neurons and fibers as well as reduced inflammation, with a high efficacy similar to drug-loaded hydrogel. Conclusion The new bioactive hydrogel serves as an effective brain injectable implant to treat PD and a promising biomaterial for developing novel strategies to treat brain diseases. Graphical Abstract
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spelling doaj.art-fb281168677d4039a78dcbc27fe02b302024-03-02T17:08:52ZengAmerican Association for the Advancement of Science (AAAS)Biomaterials Research2055-71242023-02-0127112410.1186/s40824-023-00347-0Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s diseaseJunpeng Xu0Tsai-Yu Chen1Chun-Hwei Tai2Shan-hui Hsu3Institute of Polymer Science and Engineering, National Taiwan UniversityInstitute of Polymer Science and Engineering, National Taiwan UniversityDepartment of Neurology, National Taiwan University HospitalInstitute of Polymer Science and Engineering, National Taiwan UniversityAbstract Background Parkinson’s disease (PD) is one of the most common long-term neurodegenerative diseases. Current treatments for PD are mostly based on surgery and medication because of the limitation and challenges in selecting proper biomaterials. In this study, an injectable bioactive hydrogel based on novel tannic acid crosslinker was developed to treat PD. Methods The oxidized tannic acid modified gold nano-crosslinker was synthesized and used to effectively crosslink chitosan for preparation of the bioactive self-healing hydrogel. The crosslinking density, conductivity, self-healing ability, and injectability of the hydrogel were characterized. Abilities of the hydrogel to promote the proliferation and differentiation of neural stem cells (NSCs) were assessed in vitro. Anti-inflammatory property was analyzed on J774A.1 macrophages. The hydrogel was injected in the PD rat model for evaluation of the motor function recovery, electrophysiological performance improvement, and histological repair. Results The hydrogel exhibited self-healing property and 34G (~ 80 μm) needle injectability. NSCs grown in the hydrogel displayed long-term proliferation and differentiation toward neurons in vitro. Besides, the hydrogel owned strong anti-inflammatory and antioxidative capabilities to rescue inflamed NSCs (~ 90%). Brain injection of the bioactive hydrogel recovered the motor function of PD rats. Electrophysiological measurements showed evident alleviation of irregular discharge of nerve cells in the subthalamic nucleus of PD rats administered with the hydrogel. Histological examination confirmed that the hydrogel alone significantly increased the density of tyrosine hydroxylase positive neurons and fibers as well as reduced inflammation, with a high efficacy similar to drug-loaded hydrogel. Conclusion The new bioactive hydrogel serves as an effective brain injectable implant to treat PD and a promising biomaterial for developing novel strategies to treat brain diseases. Graphical Abstracthttps://doi.org/10.1186/s40824-023-00347-0Bioactive hydrogelSelf-healingParkinson’s diseaseTannic acidGold nanoparticleConductive hydrogel
spellingShingle Junpeng Xu
Tsai-Yu Chen
Chun-Hwei Tai
Shan-hui Hsu
Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s disease
Biomaterials Research
Bioactive hydrogel
Self-healing
Parkinson’s disease
Tannic acid
Gold nanoparticle
Conductive hydrogel
title Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s disease
title_full Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s disease
title_fullStr Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s disease
title_full_unstemmed Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s disease
title_short Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s disease
title_sort bioactive self healing hydrogel based on tannic acid modified gold nano crosslinker as an injectable brain implant for treating parkinson s disease
topic Bioactive hydrogel
Self-healing
Parkinson’s disease
Tannic acid
Gold nanoparticle
Conductive hydrogel
url https://doi.org/10.1186/s40824-023-00347-0
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AT chunhweitai bioactiveselfhealinghydrogelbasedontannicacidmodifiedgoldnanocrosslinkerasaninjectablebrainimplantfortreatingparkinsonsdisease
AT shanhuihsu bioactiveselfhealinghydrogelbasedontannicacidmodifiedgoldnanocrosslinkerasaninjectablebrainimplantfortreatingparkinsonsdisease