Evaluation of the Effect of Commercial Processing on Artificial Lung Zwitterionic Coatings

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Abstract Over 15 million patients in the U.S. suffer from chronic lung diseases. These patients experience a gradual decline in respiratory function that is coupled with acute exacerbations that lead to a transient, but dangerous, worsening of their disease. Yearly, this results in 6.9 million emergency room visits, 700,000 hospitalizations, and 180,000 deaths. Unfortunately, there are less than 2,400 lung transplants every year. Thus, most of these patients will succumb to their disease without a transplant, and there is a great need for a safe, permanent means of respiratory support. To address this need, we are developing an artificial lung capable of permanent respiratory support, the pulmonary assist device (PAD). The PAD is a compact, highly biocompatible gas exchanger that, when coupled with a ventricular assist device, can provide permanent, mobile, venovenous or venoarterial extracorporeal respiratory support lasting months to years. Patients with chronic lung disease could be supported within a nursing facility or at home and return to the hospital every 2-3 or more months for scheduled PAD replacement. To accomplish this goal, the PAD must have far greater biocompatibility than current oxygenators, which cause serious bleeding complications while also failing due to clot formation within a few weeks. This is accomplished by starting with a novel, patented PAD design focused on slowing clot formation and coating it with a polycarboxybetaine (DOPA-PCB) surface coating. The DOPA-PCB coating is effective at reducing protein adsorption, platelet binding, and in vivo clot formation in artificial lungs. The next commercial phase of the coating’s development is to examine if maintains its anticoagulation function over a storage period of up to 3 months. Thus, we will determine if (1) small, DOPA-PCB coated fiber samples maintain their ability to inhibit fibrinogen adsorption and (2) if DOPA-PCB coated circuits containing miniature artificial lungs maintain their ability to slow clot formation and device functional degradation during in vivo testing for up to 3 months after coating and sterilization. Our Phase I Success Criteria are that the DOPA-PCB coating continues to (1) reduce fibrinogen adsorption by greater than 80% and (2) reduces clot weight by greater than 50% after up to 3 months of storage when compared to the uncoated control. If successful, Phase II studies will extend the described tests out to six months of storage and examine coating effectiveness during two-month sheep ECMO studies using full-scale PADs coated with either DOPA-PCB or commercial heparin coatings and stored for periods of up to 6 months. Following these studies, the coating will be ready for commercial application during traditional ECMO support or longer-term, destination therapy outside of the intensive care unit.