Development of microfabricated biohybrid artificial lung modules

Current artificial lungs, or membrane oxygenators, have limited gas exchange capacity due to their inability to replicate the microvascular scale of the natural lungs. Typical oxygenators have a surface area of 2--4 m 2, surface area to volume ratio of 30 cm-1, and gas diffusion distances of 10--30 mum. In comparison, the natural lungs have a surface area of 100 m2, surface area to volume ratio of 300 cm-1, and diffusion distances of only 1--2 mum. Membrane oxygenators also suffer from biocompatibility complications, requiring systemic anticoagulation and limiting length of use. The goal of this thesis was to utilize microfabrication and tissue engineering techniques to develop biohybrid artificial lung modules to serve as the foundation of future chronic respiratory devices. Microfabrication techniques allow the creation of compact and efficient devices while culturing endothelial cells in the blood pathways provide a more biocompatible surface. Soft lithography techniques were used to create 3-D modules that contained alternating layers of blood microchannels and gas pathways in poly(dimethylsiloxane) (PDMS). The blood microchannels were fabricated with widths of 100 mum, depths of 30 mum, and inter-channel spacing of 50 mum. The diffusion distance between the blood and gas pathways was minimized and a surface area to blood volume ratio of 1000 cm-1 was achieved. The gas permeance of the modules was examined and maximum values of 9.16 x 10-6 and 3.55 x 10-5 ml/s/cm 2/cmHg, for O2 and CO2 respectively, were obtained. Initial work examining thrombosis in non-endothelialized modules demonstrated the need for endothelial cells (ECs). Several surface modifications were explored to improve EC adhesion and growth on PDMS. Finally, endothelial cells were seeded and dynamically cultured in prototype modules. Confluent and viable cell monolayers were achieved after ten days. The work described in this thesis provides a strong foundation for creating more compact and efficient biohybrid artificial lungs devices.