Autonomous Hybrid Bioprinting of Hierarchical Perfusable Vascularized Liver Tissues - Abstract With the progress in vascular bioengineering, three-dimensional (3D) bioprinting has emerged as a potential approach for generating physiologically relevant blood vessels with the ability to grow, remodel, and repair vascular structures in vitro and in vivo. Different 3D bioprinting techniques and strategies have been investigated and established over the past years to fabricate biomimetic blood vessels and are constantly being refined and improved. To this end, sacrificial bioprinting technologies developed in the past few years have provided a convenient solution for this problem due to its capability to fabricate interconnected microchannels of arbitrary geometries and connectivity. However, although sacrificial bioprinting provides a versatile method to create vessel-like structures, there are two major obstacles preventing its further growth, i.e., the patterns attainable are relatively simple, and the resolutions attainable for the perfusable vessels are insufficient in most cases, both due to the extrusion bioprinting method that has been exclusively utilized in sacrificial bioprinting so far. We accordingly propose to develop an innovative hybrid multi-material and multi- method autonomous printing (HM2AP) technology integrating aerosol jet sacrificial printing and extrusion bioprinting, which enables facile construction of 3D complex and hierarchical vascular structures with feature sizes ranging from 10-100 µm embedded within tissue microenvironments. Successful completion of this project will build a paradigm-shifting bioprinting technology using which complex and hierarchical vessels of varying dimensions can be readily generated.
