Develop an electromagnetic-actuated, dynamic cell culture method for airway epithelial cells

PROJECT SUMMARY The airway and lung undergo dynamic stretch-relax motions in breath, cough, and airway physiotherapy. Conversely, a misplacement of airway motion contributes to severe pulmonary diseases, including postoperative pulmonary infections after chest surgery and respiratory distress syndrome from mechanical ventilation. Encouraged by clinical outcomes, efforts have been undertaken to develop research tools that culture airway epithelial cells with dynamic stretch-relax motions. In these methods, epithelial cells from the airway or lung are cultured on a porous, flexible membrane; the membrane is stretched pneumatically; and microfluidic channels function to perfuse cells and deliver pressure. However, current methods fall short in several aspects. First, the pneumatic actuation enables only basic stretch-relax motions and requires complex pressure delivery equipment. Second, the porous membrane usually requires microfabrication and a cleanroom facility. Third, the microfluidic device format prevents easy access to cell cultures and differs from standard biological protocols. To overcome these limitations and advance the science, this proposal aims to prototype an electro-magnetic actuated, dynamic airway/lung epithelial cell culture system as an insert of a 12- well plate (we named it “MagniWell-12”). In our preliminary studies, we demonstrated the effectiveness of electro-magnetic actuation of a polydimethylsiloxane (PDMS) membrane, established a protocol of laboratory fabrication of porous PDMS membrane, and confirmed biocompatibility of airway epithelial cells on the membrane. In the proposed research, we aim to integrate a porous PDMS membrane, a membrane holder, a magnetic actuator, and to develop a peripheral heat dissipation system and control circuits (Aim 1). We also plan to reveal how stretch-relax culture in the device impacts airway epithelial cell biology and function (Aim 2). Upon completion of the proposed project, we expect to deliver a novel tool for dynamic cell cultures. In the future, the device developed in this project will be broadly applied to study airway physiology and diseases (e.g., coughing and ventilation) for future R01 applications. A fully developed MagniWell-12 is expected to eventually be commercialized through potential SBIR/STTR support.