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Induced neuro-vascular interactions robustly enhance functional attributes of engineered neural implants
Biomaterials ( IF 12.8 ) Pub Date : 2018-07-04 , DOI: 10.1016/j.biomaterials.2018.07.001
Erez Shor , Uri Merdler , Inbar Brosh , Shy Shoham , Shulamit Levenberg

Engineered neural implants have a myriad of potential basic science and clinical neural repair applications. Although there are implants that are currently undergoing their first clinical investigations, optimizing their long-term viability and efficacy remain an open challenge. Functional implants with pre-vascularization of various engineered tissues have proven to enhance post-implantation host integration, and well-known synergistic neural-vascular interplays suggest that this strategy could also be promising for neural tissue engineering. Here, we report the development of a novel bio-engineered neuro-vascular co-culture construct, and demonstrate that it exhibits enhanced neurotrophic factor expression, and more complex neuronal morphology. Crucially, by introducing genetically encoded calcium indicators (GECIs) into the co-culture, we are able to monitor functional activity of the neural network, and demonstrate greater activity levels and complexity as a result of the introduction of endothelial cells in the construct. The presence of this enhanced activity could putatively lead to superior integration outcomes. Indeed, leveraging on the ability to monitor the construct's development post-implantation with GECIs, we observe improved integration phenotypes in the spinal cord of mice relative to non-vascularized controls. Our approach provides a new experimental system with functional neural feedback for studying the interplay between vascular and neural development while advancing the optimization of neural implants towards potential clinical applications.



中文翻译:

诱导的神经-血管相互作用可强有力地增强工程神经植入物的功能属性

工程神经植入物具有无数潜在的基础科学和临床神经修复应用。尽管目前有一些植入物正在进行首次临床研究,但优化其长期生存能力和功效仍然是一个公开挑战。事实证明,具有各种工程组织的血管生成前功能的植入物可以增强植入后宿主的整合,众所周知的协同神经血管相互作用表明,这种策略对于神经组织工程也很有希望。在这里,我们报告了新型的生物工程神经血管共培养构造的发展,并证明它表现出增强的神经营养因子表达和更复杂的神经元形态。至关重要的是,通过将基因编码的钙指示剂(GECI)引入共培养,我们能够监控神经网络的功能活动,并通过在构建物中引入内皮细胞来证明更高的活动水平和复杂性。这种增强活动的存在可能会导致出色的整合成果。确实,利用在GECIs植入后监测构建体发育的能力,我们观察到相对于非血管形成的对照,小鼠脊髓中的整合表型有所改善。我们的方法为功能性神经反馈提供了一个新的实验系统,用于研究血管和神经发育之间的相互作用,同时将神经植入物的优化推向潜在的临床应用。并且由于在构建物中引入了内皮细胞而显示出更高的活性水平和复杂性。这种增强活动的存在可能会导致出色的整合成果。确实,利用在GECIs植入后监测构建体发育的能力,我们观察到相对于非血管形成的对照,小鼠脊髓中的整合表型有所改善。我们的方法为功能性神经反馈提供了一个新的实验系统,用于研究血管和神经发育之间的相互作用,同时将神经植入物的优化推向潜在的临床应用。并且由于在构建物中引入了内皮细胞而显示出更高的活性水平和复杂性。这种增强活动的存在可能会导致出色的整合成果。确实,利用在GECIs植入后监测构建体发育的能力,我们观察到相对于非血管形成的对照,小鼠脊髓中的整合表型有所改善。我们的方法为功能性神经反馈提供了一个新的实验系统,用于研究血管和神经发育之间的相互作用,同时将神经植入物的优化推向潜在的临床应用。利用在GECIs植入后监测构建体发育的能力,我们观察到相对于非血管形成的对照,小鼠脊髓的整合表型有所改善。我们的方法为功能性神经反馈提供了一个新的实验系统,用于研究血管和神经发育之间的相互作用,同时将神经植入物的优化推向潜在的临床应用。利用在GECIs植入后监测构建体发育的能力,我们观察到相对于非血管形成的对照,小鼠脊髓的整合表型有所改善。我们的方法为功能性神经反馈提供了一个新的实验系统,用于研究血管和神经发育之间的相互作用,同时将神经植入物的优化推向潜在的临床应用。

更新日期:2018-07-05
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