The goal of this proposal is to combine biomedical disciplines in new approaches in an effort to design a wearable artificial pump lung (APL). The APL will provide total respiratory needs of adults with acute and chronic lung failure. This complex device relates ideally to the bioengineering research partnership initiative as it requires expertise in the allied but distinct fields of 1) blood pump and oxygenator design; 2) transmembrane mass transfer; 3) complex modeling of flow field and gas exchange; 4) nonthrombogenic coatings and their application to durable polymer-based hollow fiber membranes (HFM); 5) sensors and feedback control; 6) rapid prototyping and fabrication of HFM-based prototypes, and 7) clinically rooted biologic interface. This work should result in a keystone device that will, like the introduction of early ventricular assist devices for heart failure 20 years earlier begin a new therapeutic option for those with morbid, acute, and chronic pulmonary illnesses. Like blood pumps for heart disease, we believe that mechanical oxygenation will fit into emerging paradigms as instruments for chronic use or preferably for recovery and repair scenarios that include schemes of tissue engineering and stem cell engraftment.
The specific aims of this proposal are: 1) To use computational fluid dynamics (CFD) based multidisciplinary modeling to design and analyze the function and flow field related biocompatibility of the artificial pump-lung (APL). The function of the APL will include its ability to pump blood at 3 ~ 6 liters/minute against pressure of 20~75 mmHg and oxygen/carbon dioxide transfer of 250 ml/min at a blood flow of 5 liters/minute. Flow field biocompatibility optimization that includes limitation of stasis, hemolysis, and platelet activation and deposition will be developed by refinement of flow path geometry; 2) To validate the computationally predicted flow characteristics of the APL design in a circulatory flow loop using glycerol/water solution and to evaluate the function and flow field biocompatibility of the APL in a circulatory loop using fresh ovine blood, and 8 hour in-vivo animal studies. 3) To reduce in-vitro and in-vivo platelet activation and thrombosis by modifying blood contacting polymer surfaces of the APL device. Effectiveness and durability of heparin bonding will be compared to non heparin-based blood compatible surface coatings. The relative effects of the modifications on gas transfer of plasma resistant hollow fiber membranes (PRHFM) will be determined. 4) To perform chronic (30 day) in-vivo ovine experiments to assess the long-term function, biocompatibility and durability of the APL device and its effect on the animal. ? ? ?
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