Synthetic Alveoli for Enhanced Oxygen Delivery

University Of Colorado At Boulder, Boulder CO

Investigators

Abstract

Nontechnical: This award by the Biomaterials Program in the Division of Materials Research to the University of Colorado at Boulder is to develop new oxygen delivery methods needed to treat patients with lung and airway failure, and one promising approach is to use injectable oxygen microbubbles that mimic the natural lung structure. The research will investigate whether synthetic oxygen microbubbles can be engineered to imitate the terminal sacks (alveoli) of the lung by providing the high rate of oxygen and carbon dioxide gas exchange necessary for aerobic respiration and cellular metabolism. In all mammals, the alveoli are stabilized against collapse by a nanometer-thick membrane. This scientific investigation will experimentally determine the key nanostructural features and transport properties of this membrane as it encapsulates oxygen microbubbles. Owing to economical and regulatory concerns, synthetic compounds are favored over animal-derived materials. Therefore, this research will explore mixtures of synthetic compounds that are likely to reproduce the structure and properties of the natural lung membrane. Optimal formulations derived from this research will then be tested for their stability and gas exchange characteristics to gauge their potential biomedical performance. The project will train graduate students, undergraduates and high school students in biomaterials science and cutting-edge experimental research techniques. Additionally, an artificial lung module will be built and used as an educational demonstration unit for student projects and recruitment activities to illustrate the exciting new extrapulmonary oxygenation technologies that are being developed, as well as the need for further development of the biomaterials science field to engineer better technologies in the future. Technical: This award is to develop synthetic alveoli for extrapulmonary oxygen delivery through rational design of oxygen microbubble suspensions. Synthetic microbubble encapsulations will be engineered to mimic the lipid and peptide composition and nanostructure of natural pulmonary surfactant by providing two key properties of the alveolar lining: 1) large gas permeability; and 2) in-plane compressive rigidity. The approach taken here is to model gas permeability and monolayer collapse as thermally activated phenomena, each with a characteristic activation energy barrier. The research will first establish the target properties by characterizing the nanostructure and activation energies for oxygen permeation and collapse of natural lung surfactant on oxygen microbubbles. The parameter space for microbubbles coated with mixtures of synthetic, biomimetic compounds will be then explored by determining these activation energies and mapping them to nanostructural features. This will provide the necessary data to arrive at optimal synthetic formulations. The optimized synthetic and natural oxygen microbubble formulations will be tested for biological performance of oxygen delivery and carbon dioxide removal in an in vitro gas exchange system that allows determination of key mass transfer parameters. The research will engage graduate students, undergraduates and high school students in an interdisciplinary research program that spans chemistry, biochemistry, biomaterials, biomedical engineering, colloid science and mechanical engineering. Additionally, an artificial lung system will be built and used as an educational demonstration module for student projects and recruitment activities to illustrate the exciting biomaterials science of the lung and the urgent need for better methods of extrapulmonary oxygenation.