An Osmosis-driven 3D-printed brain implant for drug delivery.

Abstract

Glioblastoma is a highly malignant brain tumor with limited survival rates due to challenges in complete surgical excision, high recurrence (> 90%), and the inefficacy of systemic drug delivery. Significant efforts have been made to develop drug-loaded brain implants, catheters, and wafers aimed at enhancing survival rates by suppressing tumor recurrence. However, these devices often fail due to clogging, reflux, and the inability to be fully implanted intracranially. Furthermore, a lack of tissue penetration, diffusion distance, and duration of therapy have limited effectiveness of these implants. To address existing challenges, this study reports an osmosis-driven, 3D-printed brain implant with the potential for precise device customization to meet therapeutic needs, while negating systemic toxicity. It is capable of being loaded with two distinct therapeutic agents and implanted directly into the tumor resection cavity during surgery. The device features dual reservoirs, osmotic membranes, and precision-engineered needles for anchoring the device in the resection cavity and perfusing. Further, the device was characterized in vitro using 0.2% agarose gel as a brain tissue analog, with food dye as a drug analog and sodium chloride serving as an osmogen. A design of experiment approach was implemented to investigate various parameters, including membrane pore size, osmogen concentration, needle length, and their effects on release rates. The results demonstrated that the optimized implant achieves flow rates of 2.5 ± 0.1 µl/Hr and diffusion distance of up to 15.5 ± 0.4 mm, using 25 nm pore osmotic membranes with 25.3% osmogen concentration, aligning with model predictions.