Microneedles with an anisotropic porous microstructure facilitate the transdermal delivery of small molecules, lipid nanoparticles, and T cells

Porous microneedles (MNs) offer optimal performance for drug delivery and biofluid sampling. However, current porous MNs suffer from randomly interconnected pores, and existing fabrication methods lack control over pore diameter and orientation. This study employs a freeze-casting technique to precisely control these parameters in MNs, inspired by the anisotropic porous structure of wood xylem. This specialized microstructure enables rapid liquid absorption from the tips to the base within seconds, making it an effective tear-sampling tool to monitor tear biomarkers—a capability confirmed in rat models of dry-eye disease and diabetes. Additionally, these anisotropic porous MNs facilitate the active loading of various drugs, including γδ T cells, from the base to the tips without the need for specialized equipment. The delivery of γδ T cells via MNs has shown efficacy against tumors in both xenograft melanoma and pleural mesothelioma mouse models, presenting a novel approach to adoptive cell therapy.