Development of the Paracorporeal Ambulatory Assist Lung (PAAL)

Lung disease is a major healthcare problem as the third leading cause of death in the United States. Extracorporeal membrane oxygenation (ECMO) and mechanical ventilation are the only means for respiratory support once patients reach a critical condition. Confinement during these treatments causes muscle deconditioning which increases morbidity and mortality after lung transplant. Advancements in ECMO have improved treatment outcomes by introducing ambulation into the clinical practice. Current systems are cumbersome and limited to short term use. We are developing the Paracorporeal Ambulatory Assist Lung (PAAL), an artificial lung device that is durable, wearable and simplifies ambulation. The PAAL integrates a hollow fiber membrane (HFM) bundle for oxygenation and a centrifugal blood pump into a compact unit. Device size is reduced by decreasing the HFM area and increasing the oxygenation efficiency (oxygenation per unit area). This dissertation investigates passive flow, active mixing and recirculation as means for increasing oxygenation efficiency. A 1D mass-transfer model guided the choice of the HFM bundle form factor. Prototypes were manufactured for evaluating hydrodynamics, oxygenation, and hemolysis on the bench. The passive flow PAAL was selected for in-vivo testing in sheep (6-hours) while hemodynamics, oxygenation and hemolysis were assessed. The device was then optimized using computational fluid dynamics and tested for 5-days in-vivo. In-vitro performance targets were met for all proposed designs. Hemodynamics did not change relative to baseline in all in-vivo studies. The PAAL fully oxygenated blood, and plasma-free hemoglobin remained under 20 mg/dL in all in-vivo studies. Gross examination of devices after in-vivo testing showed minimal to no thrombus in the HFM bundle and no thrombus in the centrifugal pump. Platelet activation remained under 15% after 5-days. Artificial lungs incorporating passive flow, active mixing and blood recirculation have been designed. Relative to the clinical standard, HFM area was reduced by ~1.7 times using passive flow and active mixing, and by ~3 times using recirculation. An integrated and wearable PAAL was developed based on the passive flow design. This design was evaluated up to 5 days in sheep with no device related complications. Chronic (30-day) in-vivo studies on the PAAL are in progress