“Nanoscale biodegradable printing for designed tuneability of vaccine delivery kinetics”

Two photon polymerization (2PP) 3D printing enables top-down biomaterial synthesis with nanoscale spatial resolution for de novo design of monodisperse injectable drug delivery systems. To address the limitations of current 2PP resins, we developed Spatiotemporal Controlled Release Inks of Biocompatible polyEsters (SCRIBE), a novel poly(lactic- co -glycolic acid)-triacrylate resin family with sub-micron resolution and tuneable hydrolysis. SCRIBE enables direct printing of hollow microparticles with tuneable chemistry and complex geometries inaccessible to molding techniques, which we use to engineer controlled protein release in vitro and in vivo . We use SCRIBE microparticles to modulate antibody titers and class switching as a function of antigen release rate and extend these findings to enable a single-injection vaccine formulation with extended antibody induction kinetics. Demonstrating how the chemistry and CAD of 2PP-printed microparticles can be used to tune responses to biomacromolecule release in vivo opens significant opportunities for a new generation of drug delivery vehicles.