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

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- 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.