Physics-Informed Optimization for the Sub-Feature-Scale Fabrication of Hollow Microneedles via Digital Light...

Area of Science:

• Biomedical Engineering
• Materials Science
• Drug Delivery Systems

Background:

• Inner ear therapies face challenges with low bioavailability and high trauma.
• Targeted delivery across the round window membrane (RWM) is crucial for effective inner ear treatments.
• Fabricating high-aspect-ratio, small-size hollow microneedles (HMNs) for RWM delivery is technically difficult.

Purpose of the Study:

• To demonstrate the successful fabrication of small-outer-diameter HMNs using a high-resolution digital light processing (DLP) system.
• To optimize HMN structural design and fabrication parameters for enhanced performance and reliability.
• To validate the HMNs' capacity for controlled drug delivery across the RWM.

Main Methods:

• Utilized a 10 μm resolution digital light processing (DLP) system for HMN fabrication.
• Employed finite element analysis (FEA) to determine an optimal double tangent-arc transition design.
• Developed a corrected curing index (CCI) model using physics-informed regression for parameter management.
• Conducted compressive tests for structural strength and in silico/in vitro experiments for penetration performance.

Main Results:

• Successfully fabricated HMNs with mean dimensions of 805.13 μm height, 37.54 μm inner diameter, and 79.36 μm outer diameter.
• Achieved robust structural strength up to 141 mN per needle post-curing.
• Demonstrated excellent penetration performance and stable, pressure-dependent drug delivery (0.14–0.39 mL∙min⁻¹).
• The CCI model achieved high fitting accuracy (R² > 0.96).

Conclusions:

• The study successfully fabricated small-outer-diameter HMNs using DLP, addressing key fabrication challenges.
• Optimized design and a novel CCI model ensure HMN structural integrity and fabrication precision.
• Validated HMNs show promise for controlled, minimally invasive drug delivery to the inner ear via the RWM.