Aligned Biofunctional Electrospun PLGA-LysoGM1 Scaffold for Traumatic Brain Injury Repair
Aligned Biofunctional Electrospun PLGA-LysoGM1 Scaffold for Traumatic Brain Injury Repair
复制标题
用于创伤性脑损伤修复的对齐生物功能电纺 PLGA-LysoGM1 支架
DOI：
10.1021/acsbiomaterials.9b01636
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发表时间：
2020
影响因子：
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通讯作者：
Wang Yazhou
中科院分区：
文献类型：
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作者：
Tang Wei;Fang Fei;Ke Liu;Huang Zhi;Li Hui;Yin Ying;Wang Jun;Wang Guocheng;Wei Liyu;Ou Yun;Wang Yazhou
由于大脑的再生能力差，创伤性脑损伤（TBI）的治疗对现代医学提出了严峻的挑战。目前迫切需要能够支持神经元生长、引导神经突伸长和重建受损脑组织的生物功能支架。为此，我们开发了一种对齐的生物功能支架（aPLGA-LysoGM 1），其中聚（乳酸-羟基乙酸）（PLGA）与鞘脂神经酰胺N-脱酰酶（SCDase）水解的单唾液酸四己糖神经节苷脂（LysoGM 1）功能化，并使用静电纺丝形成对齐的纤维网络。作为神经元膜的神经节苷脂，功能化的LysoGM 1赋予支架独特的生物学特性，有利于神经元的生长和受损脑组织的再生。此外，我们发现对齐的PLGA-LysoGM 1纤维作为地形学线索来引导神经突延伸，这对于组织突触网络（神经网络）的形成至关重要。系统的体外研究表明，对齐的生物功能支架促进神经元活力，神经突生长和突触形成，并保护神经元免受压力相关的损伤。此外，在大鼠TBI模型中，我们证明了aPLGA-LysoGM 1支架的植入支持脑损伤的恢复，因为与替代支架相比，发现更多的内源性神经元迁移和浸润到缺损区中。这些结果表明，对齐的生物功能性aPLGA-LysoGM 1支架代表了TBI后脑组织再生的有希望的治疗策略。
Due to poor regenerative capabilities of the brain, a treatment for traumatic brain injury (TBI) presents a serious challenge to modern medicine. Biofunctional scaffolds that can support neuronal growth, guide neurite elongation, and re-establish impaired brain tissues are urgently needed. To this end, we developed an aligned biofunctional scaffold (aPLGA-LysoGM1), in which poly (lactic-co-glycolic acid) (PLGA) was functionalized with sphingolipid ceramideN-deacylase (SCDase)-hydrolyzed monosialotetrahexosylganglioside (LysoGM1) and electrospinning was used to form an aligned fibrous network. As a ganglioside of neuronal membranes, the functionalized LysoGM1 endows the scaffold with unique biological properties favoring the growth of neuron and regeneration of injured brain tissues. Moreover, we found that the aligned PLGA-LysoGM1 fibers acted as a topographical cue to guide neurite extension, which is critical for organizing the formation of synaptic networks (neural networks). Systematic in vitro studies demonstrated that the aligned biofunctional scaffold promotes neuronal viability, neurite outgrowth, and synapse formation and also protects neurons from pressure-related injury. Additionally, in a rat TBI model, we demonstrated that the implantation of aPLGA-LysoGM1 scaffold supported recovery from brain injury, as more endogenous neurons were found to migrate and infiltrate into the defect zone compared with alternative scaffold. These results suggest that the aligned biofunctional aPLGA-LysoGM1 scaffold represents a promising therapeutic strategy for brain tissue regeneration following TBI.