A Dual‐Layered Microfluidic System for Long‐Term Controlled In Situ Delivery of Multiple Anti‐Inflammatory Factors for Chronic Neural Applications. (20th September 2017)

• Record Type: Journal Article
• Authors: Frey, Laura; Bandaru, Praveen; Zhang, Yu Shrike; O'Kelly, Kevin; Khademhosseini, Ali; Shin, Su Ryon
• Is Part Of: Advanced functional materials. Volume 28:Number 12(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-09-20
• Subjects: astrocytes -- drug delivery -- hydrogels -- microfluidic system -- neural electrodes -- neural probes; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201702009
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: 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. Abstract : A dual‐layered microfluidic coating for neural probes is developed, consisting of a hydrogel and a porous membrane to allow for sustained, steady diffusion of multiple anti‐inflammatory factors into the surrounding brain tissue. In vitro models indicate that repeated infusions of interleukin‐4 through such a system increase anti‐inflammatory M2 macrophage phenotypes and decrease pro‐inflammatory markers in astrocytes over a 3‐week culture.