Helical neural implants for intracerebral drug delivery.

Abstract

Objective.Neurological disorders often arise from specific regions of dysfunction in the brain. One approach to target these pathologic regions is through chemical delivery using intracerebral implants. Previous works have designed implants that are small and flexible, minimizing the mechanical mismatch between inorganic implants and soft organic brain tissue. Most of these implants are simple cylindrical catheters with inflow and outflow ports at either end of the cylinder. This limits the region and volume of tissue that can be dosed. We sought to develop novel catheter designs that permit targeting of larger volumes of brain tissue while maintaining minimal footprint to minimize gliosis.Approach.We present the design, fabrication, and testing of a novel helical-shaped microfluidic catheter we term SPIRAL (Strategic Precision Infusion for Regional Administration of Liquid). SPIRAL leverages rational fluidic design of multiple fluid outflow ports to vary infused fluid spatial distribution across brain regions. We usedin silico, in vitro, and in vivomodels to test the fluid dynamic functionality and chronic viability of SPIRAL.Results.Our computational fluid dynamics (CFDs) models illustrate how SPIRAL can be configured to permit simultaneous dosing through multiple outflow ports yielding a variable fluid distribution compared to a straight catheter. We show how CFDin silicomodels can be used to optimize dimensions of channel openings across SPIRAL, to achieve uniform flow through channels and validate these resultsin vitro. We show how chronically implanted SPIRAL catheters do not increase gliosis compared to standard straight catheters of similar dimensions or materials.Significance.Our helical intracerebral drug delivery catheter facilitates fluid localization while maintaining minimal invasiveness. SPIRAL could enable multiregional brain access and improve therapeutic efforts in the treatment of neurological diseases.