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Anatomically Inspired Three-dimensional Micro-tissue Engineered Neural Networks for Nervous System Reconstruction, Modulation, and Modeling
Published on: May 31, 2017
Implantation of biomimetic polydopamine nanocomposite scaffold promotes optic nerve regeneration through modulating
Tonghe Pan1,2, Yate Huang1,2, Jinfei Wei1
1State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
Abstract:
Optic nerve regeneration remains challenging worldwide due to the limited intrinsic regenerative capacity of retinal ganglion cells (RGCs) and the inhibitory microenvironment. Oxidative stress, induced by excessive reactive oxygen species (ROS) following optic nerve injury, is associated with prolonged neuroinflammation, resulting in a secondary injury of RGCs and the impairment of axon regeneration. Herein, we developed a bionic nanocomposite scaffold (GA@PDA) with immunoregulatory ability for enhanced optic nerve regeneration. The ice-templating method was employed to fabricate biopolymer-based scaffolds with a directional porous structure, mimicking the optic nerve, which effectively guided the oriented growth of neuronal cells. The incorporation of bioinspired polydopamine nanoparticles (PDA NPs) further confers excellent ROS scavenging ability, thereby modulating the phenotype transformation of microglia/macrophages from pro-inflammatory M1 to anti-inflammatory M2. In a rat optic nerve crush model, the implantation of GA@PDA scaffold enhanced survival of RGCs and promoted axonal regeneration. Our study offers novel insights and holds promising potential for the advancement of engineered biomaterials in facilitating optic nerve regeneration.
Insights
A novel bionic scaffold (GA@PDA) promotes optic nerve regeneration by reducing oxidative stress and inflammation. This engineered biomaterial enhances retinal ganglion cell survival and axon regrowth in rats.
Area of Science:
- Biomaterials Science
- Neuroscience
- Regenerative Medicine
Background:
- Optic nerve regeneration is hindered by limited retinal ganglion cell (RGC) intrinsic capacity and a hostile microenvironment.
- Oxidative stress and neuroinflammation post-injury exacerbate RGC damage and impede axon regeneration.
Purpose of the Study:
- To develop an immunoregulatory bionic nanocomposite scaffold (GA@PDA) for enhanced optic nerve regeneration.
- To investigate the scaffold's ability to mitigate oxidative stress and modulate neuroinflammation.
Main Methods:
- Fabrication of a biopolymer-based scaffold with a directional porous structure using ice-templating.
- Incorporation of polydopamine nanoparticles (PDA NPs) for ROS scavenging.
- Evaluation in a rat optic nerve crush model.
Main Results:
- The GA@PDA scaffold guided oriented neuronal cell growth.
- PDA NPs effectively scavenged reactive oxygen species (ROS), shifting microglia/macrophages from M1 to M2 phenotype.
- Scaffold implantation improved RGC survival and promoted axonal regeneration in vivo.
Conclusions:
- The GA@PDA bionic scaffold demonstrates significant potential for promoting optic nerve regeneration.
- This engineered biomaterial offers a promising strategy for addressing challenges in RGC survival and axon regrowth.
- The study provides novel insights into using immunoregulatory scaffolds for neural repair.
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