VAPOR Bioreactors for In Vitro Vascularization of FRESH 3D Bioprinted Collagen Tissues

In recent decades, the field of regenerative medicine has aimed to generate patient-specific tissues to treat various diseases, injuries, and improve drug development. Unfortunately, most engineering strategies are limited to thin 2D cell sheets that have resulted in minimal translational success. The failure to generate large (≥1 cm³) tissues stems from the inability to generate microvasculature for nutrient delivery which constrains tissue thickness to the limits of passive nutrient diffusion (~250 µm). This work aims to bridge the macro (>1 mm) and the micro (<1 mm) length scales of vascular engineering to create true multi-scale vasculature. Using freeform reversible embedding of suspended hydrogels (FRESH), I 3D bioprint millimeter-scale collagen vessels and integrate them with micron-scale cell-assembled capillaries. To achieve integration of the engineered vessels with cell-assembled capillaries, I developed a bioreactor system termed vasculature and perfusion organ-on-a-chip reactor (VAPOR) to perfuse FRESH printed collagenbased high-resolution internally perfusable scaffolds (CHIPS). This dissertation examines how the VAPOR perfusion of CHIPS containing a porous cell-ECM hydrogel drives angiogenesis to generate multi-scale vascularized tissues in vitro. The result of this work is a highly modular tissue engineering platform that can produce larger microvascularized human tissues for next-generation organ-specific research, repair, and drug development.