Multi-compartment bioartificial organs engineered via iterative sacrificial 3D printing and vascular integration

Several biofabrication strategies have emerged to incorporate vascular networks within bioartificial tissues. Significant challenges emerge when considering clinical implementation, such as allogeneic graft rejection, as well as achieving adequate perfusion and integration with the endogenous vasculature of human-scale tissues. We propose iterative sacrificial 3D printing and polymer casting to create modular convection-enhanced therapeutic cell delivery systems. The resulting multi-compartment devices comprise a porous vascular graft with controlled geometry and branching, along with an external cell-loading compartment. The devices can be autoclaved, stored, and filled with cell-laden hydrogels for long-term in vitro culture or transplantation. Bioreactor perfusion studies with insulin-secreting β cells showed the potential of this strategy in achieving rapid secretory response dynamics and stem cell-derived islet maturation. Transplantation as iliac arteriovenous shunts in pigs indicated safety and patency. Multi-compartment vascular devices could serve as off-the-shelf human-scale bioartificial organs for extended in vitro culture studies and for transplantation.