High-Precision 3D Printing of Microporous Cochlear Implants for Personalized Local Drug Delivery

Abstract

Hearing loss is a highly prevalent multifactorial disorder affecting 20% of the global population. Current treatments using the systemic administration of drugs are therapeutically ineffective due to the anatomy of the cochlea and the existing blood–labyrinth barrier. Local drug delivery systems can ensure therapeutic drug concentrations locally while preventing adverse effects caused by high dosages of systemically administered drugs. Here, we aimed to design, fabricate, and characterize a local drug delivery system for the human cochlea. The design was relevant to the size of the human ear, included two different shapes, and incorporated two different microporous structures acting as reservoirs for drug loading and release. The four cochlear implant designs were printed using the two-photon polymerization (2PP) technique and the IP-Q photoresist. The optimized 2PP process enabled the fabrication of the cochlear implants with great reproducibility and shape fidelity. Rectangular and cylindrical implants featuring cylindrical and tapered tips, respectively, were successfully printed. Their outer dimensions were 0.6 × 0.6 × 2.4 mm3 (L × W × H). They incorporated internal porous networks that were printed with high accuracy, yielding pore sizes of 17.88 ± 0.95 μm and 58.15 ± 1.62 μm for the designed values of 20 μm and 60 μm, respectively. The average surface roughness was 1.67 ± 0.24 μm, and the water contact angle was 72.3 ± 3.0°. A high degree of polymerization (~90%) of the IP-Q was identified after printing, and the printed material was cytocompatible with murine macrophages. The cochlear implants designed and 3D printed in this study, featuring relevant sizes for the human ear and tunable internal microporosity, represent a novel approach for personalized treatment of hearing loss through local drug delivery.

Multi-scale in silico and ex silico mechanics of 3D printed cochlear implants for local drug delivery

“…In this study, upscaled models of recently developed porous cochlear implant designs ( Isaakidou et al, 2023 ) were modified and fabricated specifically for torsion testing. Four different specimen types were developed, namely, 8R, 16R, 32R, and 32R60, where the letter ‘R’ (rectangular) represents the implant type, the number preceding it (8, 16, or 32) corresponds to the scaling factor relative to the actual implant size, and the subsequent number after the letter R (if present) indicates the pore size (in μm) in the original porous design ( Figure 2A ).…”

“…Cochlear implants, with anatomically relevant sizes for the human ear ( i.e. , 0.6 × 0.6 × 2.4 mm³), incorporating a drug reservoir and an implantable tip, have been recently developed as an alternative solution to the existing drug delivery methods by using two-photon polymerization (2PP) ( Isaakidou et al, 2023 ). The implant shapes were rectangular (R) and cylindrical (C) featuring cylindrical tips ( Figure 1A ).…”