Synergistic Combination of Additive One- and Two-Photon Polymerization Printing Methods to Fabricate 3D Microstructured Perfusable Angiogenesis-on-a-Chip Systems.

Tissue engineering, and in particular the development of organ-on-a-chip (OOC) models, holds significant promise for advancing personalized medicine and reducing the use of animal models. The integration of microfluidics and advanced biomaterials in OOC systems provides controlled microenvironments and fosters the creation of physiologically relevant tissue models. A critical aspect of OOC models is the fabrication of perfusable chips to create vascular networks that are essential for sustaining long-term 3D cultures. Here we show a two-step fabrication approach that combines one- and two-photon polymerization (2PP) to create a microfluidic chip capable of supporting endothelial cell (EC) angiogenesis. The chip features a 2PP-printed sealing contour to ensure leak-free bonding of chip parts, and an array of channel-separating-pillars that enable EC migration from the parent vessel into an extracellular matrix. Our results demonstrate that the developed angiogenesis-on-a-chip model successfully induces EC sprouting in response to angiogenic factors. This work significantly contributes to the field by providing a versatile platform for vascular studies, highlighting the potential for its application in drug screening. The flexibility and precision of our fabrication method also allows for customizing OOC devices for various biological applications, thereby enhancing the relevance of these systems in investigation of complex tissue interactions.