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 m2, surface area to volume ratio of 30 cm-1, and gas diffusion distances of 10 - 30 microns. 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 microns. 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 microns, depths of 30 microns, and inter-channel spacing of 50 microns. 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/cm2/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.
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机译：当前的人工肺或膜氧合器由于不能复制天然肺的微血管垢而具有有限的气体交换能力。典型的充氧器的表面积为2至4平方米，表面积与体积之比为30 cm-1，气体扩散距离为10至30微米。相比之下，天然肺的表面积为100平方米，表面积与体积之比为300 cm-1，扩散距离仅为1-2微米。膜式充氧器还具有生物相容性并发症，需要全身性抗凝和限制使用时间。本文的目的是利用微细加工和组织工程技术开发生物混合人工肺模块，以作为未来慢性呼吸装置的基础。微细加工技术允许创建紧凑而高效的设备，同时在血液通路中培养内皮细胞，从而提供了更具生物相容性的表面。使用软光刻技术来创建3-D模块，该模块包含聚二甲基硅氧烷（PDMS）中血液微通道和气体通道的交替层。血液微通道的宽度为100微米，深度为30微米，通道间间距为50微米。血液和气体通道之间的扩散距离最小，并且表面积与血液的体积比达到1000 cm-1。检查了组件的气体渗透率，对于O 2和CO 2分别获得了9.16 x 10-6和3.55 x 10-5 ml / s / cm2 / cmHg的最大值。检查非内皮模块中血栓形成的最初工作表明需要内皮细胞（EC）。探索了几种表面改性方法，以改善EC在PDMS上的粘附和生长。最后，将内皮细胞播种并在原型模块中动态培养。十天后达到汇合和活细胞单层。本文所描述的工作为建立更紧凑，更高效的生物混合人工肺装置提供了坚实的基础。
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