• 3D printing
• Alveoli
• Biomaterials
• Electrospinning
• Lung
• Membrane
• Polymer
• Polymeric solution

The blood-gas barrier (BGB) is the functional component of the pulmonary alveoli that is interposed between the air present in the alveolar chambers and the blood, which flows through the capillaries of the pulmonary vasculature. The BGB is mainly populated by alveolar epithelial cells on the outer part and endothelial cells on the inner part and diffusion of gases across it is favoured by its large exchange surface (≈ 70 m2) and thinness (< 1 μm). Understanding the functionality of the BGB is essential for understanding the lung development, its physiology, physiopathology, and diseases. Animal experimentation has been useful for this purpose but presents a number of limits, i.e., the variability between different subjects and the complexity of biological systems, which make the interpretation of the results difficult. In this perspective, in vitro models may provide a platform for studying the responses of biological systems to chemical, physical and biological stimuli in a more controllable and repeatable way. In view of this, in vitro models of the BGB can be designed with increasingly layers of complexity to better recapitulate its microenvironment. One of the most relevant aspects is the 3-dimensionality and, in particular, the surface curvature in near-cell range plays a key role in influencing the cell behaviour. In order to achieve a membrane by mimicking the most relevant aspects of this structure, but to consider the small dimensions of the human alveolar chambers in the order of 200 μm, this work proposes a combination of the masked stereolithography appearance (MSLA) 3D printing and the electrospinning (ES) processing technologies. The MSLA 3D printing can rapidly produce objects with a high resolution (≈50 μm) by selective photopolymerization layer-by-layer, but at the same time final material is hard, brittle, and not biocompatible. On the other hand, ES can produce ultrathin fibres which resemble the ECM structure, with their high porosity and large surface area, but there is no control in the final topology.
The combination of the two methods allows to join the versatility and controllability of the targeted 3D printed structures, with the ECM-like structural features of the electrospun mesh that can be made of a vast range of spinnable biomaterials. In this work, the random block copolymer polyethylene oxide terephthalate/polybutylene terephthalate (PEOT-PBT) is proposed as candidate material because of its biocompatibility (reported both in vitro and in vivo), spinnability, hydrophilicity, and mechanical properties. To our best knowledge, PEOT-PBT has never been used for lung tissue engineering applications.