Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s disease
Open accessAbstract
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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Direct application of TA is constrained by poor stability and susceptibility to oxidation.
“However, the direct application of TA is constrained by limitations such as poor stability and susceptibility to oxidation26,27.”
From Intelligence-responsive wettability switch coating on magnesium implants for treating osteoporotic fracture (2026) · cites this paper as [27]
The Methods and Results describe oxidation of tannic acid by laccase, supporting that TA can be oxidized under those conditions. The Discussion describes the resulting oxidized TA as relatively stable, but does not say that unmodified TA has poor stability or that oxidation constrains its direct application. Page numbers are unavailable in our copy. (LLM, conf=0.78)
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- Authors
- Xu, J., Chen, T.-Y., Tai, C.-H., & Hsu, S.-H.
- Affiliations
- National Taiwan University (TW)
- National Taiwan University Hospital (TW)
- National Health Research Institutes (TW)
- Corresponding author
- Tai, Chun-Hwei
- Hsu, Shan-hui
- Venue
- Biomaterials Research
- Published
- 2023-02-08
- Volume
- 27
- Issue
- 1
- Pages
- 8-8
- ISSN
- 1226-4601 (ISSN-L)
- 2055-7124
- PMC
- PMC9909866
- OpenAlex
- W4319459773
- Cited by
- 57
- References
- 71
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 17 · 2023: 9
- FWCI
- 4.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Biomaterials Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science and Technology Council, Taiwan, Republic of China (NSTC 111-2221-E-002-052-MY3)
- National Taiwan University (NTU-CC-111L892501)
- National Synchrotron Radiation Research Center (NSRRC), Republic of China (2022-1-042-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Keywords
- Parkinson's disease, self-healing hydrogels, tannic acid, chitosan, neural stem cells, anti-inflammatory activity, antioxidant activity, motor recovery, subthalamic nucleus, tyrosine hydroxylase, neuroprotection, biomaterials
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