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A Dual-layered Microfluidic System for Long-term Controlled In Situ Delivery of Multiple Anti-inflammatory Factors for Chronic Neural Applications.
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2017-09-20 , DOI: 10.1002/adfm.201702009
Laura Frey 1 , Praveen Bandaru 1 , Yu Shrike Zhang 1 , Kevin O'Kelly 1 , Ali Khademhosseini 1 , Su Ryon Shin 1
Affiliation  

This study reports the development of a microfluidic system capable of repeated infusions of anti‐inflammatory factors post‐implantation for use as a coating for neural probes. This system consists of a microchannel in a thin gelatin methacryloyl–polyethylene glycol composite hydrogel surrounded by a porous polydimethylsiloxane membrane, where the hydrogel can be dried to increase the stiffness for easy insertion. Reswelling allows the perfusion of interleukin (IL)‐4 and dexamethasone as anti‐inflammatory factors through the channel with minimal burst release and significant amounts of IL‐4 are observed to release for up to 96 h post‐infusion. Repeated injections of IL‐4 increase the ratio of prohealing M2 versus proinflammatory M1 phenotypes of macrophages encapsulated in the hydrogel by sixfold compared with a single injection, over a 2‐week period. These repeated infusions also significantly downregulate the expression of inflammatory markers tumor necrosis factor‐α and IL‐6 in astrocytes encapsulated in hydrogel. To demonstrate the system as a coating of neural probes for in vivo applications, a prototype device is further fabricated, where a thin dual‐layered microfluidic system is integrated onto a metal probe. Such a drug delivery system can help reduce the formation of a glial scar around neural probes.

中文翻译:


用于长期受控原位输送多种抗炎因子的双层微流体系统,用于慢性神经应用。



这项研究报告了一种微流体系统的开发,该系统能够在植入后重复输注抗炎因子,用作神经探针的涂层。该系统由薄明胶甲基丙烯酰-聚乙二醇复合水凝胶中的微通道组成,周围环绕着多孔聚二甲基硅氧烷膜,水凝胶可以在其中干燥以增加刚度以便于插入。再溶胀允许白细胞介素 (IL)-4 和地塞米松作为抗炎因子通过通道灌注,并以最小的爆发释放,并且观察到在输注后长达 96 小时内释放大量的 IL-4。在两周内,重复注射 IL-4 可使包裹在水凝胶中的巨噬细胞的促愈合 M2 与促炎 M1 表型的比率比单次注射增加六倍。这些重复输注还显着下调水凝胶封装的星形胶质细胞中炎症标志物肿瘤坏死因子-α 和 IL-6 的表达。为了证明该系统作为体内应用的神经探针涂层,进一步制造了原型设备,其中将薄的双层微流体系统集成到金属探针上。这种药物输送系统可以帮助减少神经探针周围神经胶质疤痕的形成。
更新日期:2017-09-20
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