Enhanced biocompatibility of neural probes by integrating microstructures and delivering anti-inflammatory agents via microfluidic channels
Enhanced biocompatibility of neural probes by integrating microstructures and delivering anti-inflammatory agents via microfluidic channels
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DOI：
10.1088/1741-2552/aa52dc
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发表时间：
2017-04-01
影响因子：
4
通讯作者：
Zhang, Jinsheng
中科院分区：
文献类型：
--
作者：
Liu, Bin;Kim, Eric;Zhang, Jinsheng
Objective.生物相容性是慢性神经植入物的主要问题，涉及神经元和神经胶质细胞的炎症和伤口愈合反应。为了增强生物相容性，我们开发了具有开放结构电极、微流体通道和用于药物递送以抑制组织反应的储库的硅-聚对二甲苯混合神经探针。Approach.我们将我们的神经探针长期植入大鼠听觉皮层，并研究（1）开放结构电极是否通过测量神经胶质反应减少炎症反应;和（2）抗生素米诺环素的递送是否减少炎症和组织反应。植入后4周，对胶质细胞酸性蛋白（星形胶质细胞标志物）和电离钙结合衔接分子1（巨噬细胞/小胶质细胞标志物）进行免疫染色，以鉴定免疫反应性星形胶质细胞和小胶质细胞，并确定星形胶质细胞和小胶质细胞反应/活化的程度。使用传统的固体表面电极和新设计的电极之间进行了比较，以及米诺环素和人工脑脊髓液通过微流体通道扩散之间的交付。主要结果。植入后4周，与传统电极相比，具有集成微结构的新探针引起的组织反应最小。通过集成微流体通道递送的微环素减少了组织反应，如植入的神经探针周围的小胶质细胞反应减少所示。意义新的设计将有助于提高植入式设备的长期稳定性。
Objective. Biocompatibility is a major issue for chronic neural implants, involving inflammatory and wound healing responses of neurons and glial cells. To enhance biocompatibility, we developed silicon-parylene hybrid neural probes with open architecture electrodes, microfluidic channels and a reservoir for drug delivery to suppress tissue responses. Approach. We chronically implanted our neural probes in the rat auditory cortex and investigated (1) whether open architecture electrode reduces inflammatory reaction by measuring glial responses; and (2) whether delivery of antibiotic minocycline reduces inflammatory and tissue reaction. Four weeks after implantation, immunostaining for glial fibrillary acid protein (astrocyte marker) and ionizing calcium-binding adaptor molecule 1 (macrophages/microglia cell marker) were conducted to identify immunoreactive astrocyte and microglial cells, and to determine the extent of astrocytes and microglial cell reaction/activation. A comparison was made between using traditional solid-surface electrodes and newly-designed electrodes with open architecture, as well as between deliveries of minocycline and artificial cerebral-spinal fluid diffused through microfluidic channels. Main results. The new probes with integrated micro-structures induced minimal tissue reaction compared to traditional electrodes at 4 weeks after implantation. Microcycline delivered through integrated microfluidic channels reduced tissue response as indicated by decreased microglial reaction around the neural probes implanted. Significance. The new design will help enhance the long-term stability of the implantable devices.