Multiscale Hybrid Fabrication: Volumetric Printing Meets Two‐Photon Ablation

Abstract Multiscale printing of 3D perfusable geometries holds great potential for a range of applications, from microfluidic systems to organ‐on‐a‐chip. However, the generation of freeform designs spanning from centimeter to micrometer features represents an unmet challenge for a single fabrication method and thus may require the convergence of two or more modalities. Leveraging the great advances in light‐based printing, herein a hybrid strategy is introduced to tackle this challenge. By combining volumetric printing (VP) and high‐resolution two‐photon ablation (2PA), the possibility to create multiscale models with features ranging from mesoscale (VP) to microscale (2PA) is demonstrated. To successfully combine these two methods, micrometer‐size defects generated during the VP process due to optical modulation instability and self‐focusing phenomena are first eliminated. By optical tuning the refractive index of the photoresin, defect‐free VP that can then be combined with 2PA is demonstrated. To facilitate the 2PA process and meet VP requirements, a purely protein‐based photoclick photoresin combining gelatin‐norbornene and gelatin‐thiol is introduced. Finally, the possibility to generate complex organotypic 3D vasculature‐like constructs with features ranging from ≈400 µm of VP to ≈2 µm of 2PA is demonstrated. This hybrid strategy opens new possibilities for multiscale printing, with particular potential for microfluidics and organ/tissue‐on‐a‐chip technologies.