3 years ago

A Dual-Layered Microfluidic System for Long-Term Controlled In Situ Delivery of Multiple Anti-Inflammatory Factors for Chronic Neural Applications

A Dual-Layered Microfluidic System for Long-Term Controlled In Situ Delivery of Multiple Anti-Inflammatory Factors for Chronic Neural Applications
Su Ryon Shin, Laura Frey, Yu Shrike Zhang, Kevin O'Kelly, Praveen Bandaru, Ali Khademhosseini
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. 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adfm.201702009

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