Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Nat Mater. 2019 May;18(5):510-517. doi: 10.1038/s41563-019-0292-9. Epub 2019 Feb 25.
As an important application of functional biomaterials, neural probes have contributed substantially to studying the brain. Bioinspired and biomimetic strategies have begun to be applied to the development of neural probes, although these and previous generations of probes have had structural and mechanical dissimilarities from their neuron targets that lead to neuronal loss, neuroinflammatory responses and measurement instabilities. Here, we present a bioinspired design for neural probes-neuron-like electronics (NeuE)-where the key building blocks mimic the subcellular structural features and mechanical properties of neurons. Full three-dimensional mapping of implanted NeuE-brain interfaces highlights the structural indistinguishability and intimate interpenetration of NeuE and neurons. Time-dependent histology and electrophysiology studies further reveal a structurally and functionally stable interface with the neuronal and glial networks shortly following implantation, thus opening opportunities for next-generation brain-machine interfaces. Finally, the NeuE subcellular structural features are shown to facilitate migration of endogenous neural progenitor cells, thus holding promise as an electrically active platform for transplantation-free regenerative medicine.
作为功能生物材料的重要应用,神经探针在研究大脑方面做出了重要贡献。受生物启发和仿生策略已开始应用于神经探针的开发,尽管这些和以前几代的探针与神经元靶标在结构和机械上存在差异,导致神经元丢失、神经炎症反应和测量不稳定。在这里,我们提出了一种神经探针的仿生设计——类神经元电子(NeuE),其中关键的构建模块模拟了神经元的亚细胞结构特征和机械特性。植入的 NeuE-大脑接口的全三维映射突出了 NeuE 与神经元之间的结构不可区分性和紧密的相互渗透。时变组织学和电生理学研究进一步揭示了在植入后不久与神经元和神经胶质网络具有结构和功能稳定的接口,从而为下一代脑机接口开辟了机会。最后,NeuE 的亚细胞结构特征被证明有利于内源性神经祖细胞的迁移,因此有望成为一种无需移植的再生医学的电活性平台。