Polymerized Pro‐Estrogen Microneedles via Two Photon Polymerization

Abstract

ABSTRACT Two‐photon polymerization (TPP) is a powerful technique to create microscale structures with high precision, offering significant potential in tissue engineering and drug delivery. While conventional TPP‐fabricated drug carriers rely on passive encapsulation, these systems often suffer from low payload capacity and diffusion‐controlled release kinetics. To address these challenges, we present the first demonstration of TPP‐printed polyprodrug microstructures, where the therapeutic agent is covalently integrated into the polymer network as the repeating unit itself. Estrogen‐based diacrylate monomers derived from 17β‐estradiol were synthesized via one‐step esterification/transesterification to create a photocurable resin. Curing under flood UV irradiation yielded a rigid thermoset (E′ ∼2.5 GPa at 25°C) with a glass transition temperature of about 50°C. Using TPP, we fabricated various microscale needles (100 × 100 × 400 µm, 2 µm resolution) from this resin, enabling direct printing of intrinsically therapeutic microstructures without post‐processing drug loading. The cured polymer acts as both a structural matrix and a hydrolytically degradable polyprodrug, releasing estradiol through cleavage of ester bonds. By combining covalent drug‐polymer integration with high‐resolution 3D printing, this work establishes a platform for personalized transdermal drug delivery devices with spatially controlled release profiles determined by microstructure design and polymer degradation kinetics.