GEOMETRIC DETERMINANTS OF CELL VIABILITY FOR 3D-PRINTED HOLLOW MICRONEEDLE ARRAY-MEDIATED DELIVERY.

A wide range of emerging biomedical applications and clinical interventions rely on the ability to deliver living cells via hollow, high-aspect-ratio microneedles. Recently, microneedle arrays (MNA) have gained increasing interest due to inherent benefits for drug delivery; however, studies exploring the potential to harness such advantages for cell delivery have been impeded due to the difficulties in manufacturing high-aspect-ratio MNAs suitable for delivering mammalian cells. To bypass these challenges, here we leverage and extend our previously reported hybrid additive manufacturing (or "three-dimensional (3D) printing) strategy-i.e., the combined the "Vat Photopolymerization (VPP)" technique, "Liquid Crystal Display (LCD)" 3D printing with "Two-Photon Direct Laser Writing (DLW)"-to 3D print hollow MNAs that are suitable for cell delivery investigations. Specifically, we 3D printed four sets of 650 μm-tall MNAs corresponding to needle-specific inner diameters (IDs) of 25 μm, 50 μm, 75 μm, and 100 μm, and then examined the effects of these MNAs on the post-delivery viability of both dendritic cells (DCs) and HEK293 cells. Experimental results revealed that the 25 μm-ID case led to a statistically significant reduction in post-MNA-delivery cell viability for both cell types; however, MNAs with needle-specific IDs ≥ 50 μm were statistically indistinguishable from one another as well as conventional 32G single needles, thereby providing an important benchmark for MNA-mediated cell delivery.