The long-term goal of this technology development project is to improve rehabilitation of Veterans suffering from lung disease through the development of the first truly portable, biocompatible, artificial lung capable of short and long term respiratory support. Current artificial lungs have recently been used to rehabilitate lung disease patients; however, significant advances in gas exchange, biocompatibility, and portability are required to fully realize their potential. Microfluidic artificial lungs promise to enable a new class of truly portable artificial lungs through feature sizes and blood channel designs that closely mimic those found in their natural counterpart. However, current microfabrication techniques limit the microfluidic networks in these devices to two dimensions, thereby severely limiting potential device topologies and resulting in inefficient blood distribution networks. Further, current construction techniques may not be suitable for the large area production required for human applications. In this study, we will for the first time harness high resolution 3D polymer printing technology to create large area microfluidic lungs with truly three dimensional blood flow networks and topologies. Constructed 3D printed microfluidic artificial lungs will exhibit gas exchange suitable for some human applications, while using a fraction of the blood contacting surface area, blood volume, and total volume of current commercial devices. The objectives of the current technology-development Merit proposal are thus to: 1) optimize resin [resolution, permeability, toxicity, and blood compatibility] for microfluidic artificial lungs; 2) Construct an adult-scale 3D printed microfluidic lung and validate in vitro; and, 3) Acute and chronic in vivo testing of an adult-scale µAL. At the conclusion of this study, we will be ready to for extended testing of our 3D printed microfluidic artificial lungs in a large animal model and for scaling up to larger rated blood flows. The listed objectives are thus critical to advancing this promising technology towards initial acute systems for Veteran pulmonary rehabilitation.