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Development of a Lung-on-a-Chip Platform for Animal-Free Evaluation of Polymer Lung Surfactants through In Vitro-In Vitro-In Vivo Correlation (IVIVIVC)

Project Description

Respiratory distress syndrome (RDS) and acute respiratory distress syndrome (ARDS) remain major causes of respiratory failure. Although pulmonary surfactant replacement has transformed neonatal RDS treatment, its effectiveness in adult lung injury is limited by the susceptibility of lipid-based surfactants to inhibition. The Won Laboratory has developed polymer lung surfactants (PLSs) based on block copolymer micelles that exhibit exceptional surface activity and resistance to deactivation.

However, PLS development still relies heavily on animal studies because existing in vitro models do not reproduce the dynamically breathing alveolar environment while enabling quantitative assessment of surfactant mechanics. Leveraging Prof. Park’s expertise in organoids and organ-on-a-chip technologies, this project will develop a lung-on-a-chip alveolar model capable of cyclic expansion and contraction and quantitative pressure-volume (PV) measurements.

The collaboration will establish an in vitro–in vitro–in vivo correlation (IVIVIVC) linking conventional surface pressure-area isotherms, lung-on-a-chip PV mechanics, and pulmonary mechanics in mouse models. This predictive platform will enable rapid screening and mechanistic evaluation of PLSs while reducing animal use, ultimately accelerating the development of next-generation pulmonary surfactant therapeutics.

Start Date

June 1, 2027 (or appropriate date)

Postdoc Qualifications

The ideal postdoctoral researcher will have a strong background in biomedical engineering, tissue engineering, biomaterials, microfluidics, organ-on-a-chip technologies, or pulmonary physiology. Experience with mammalian cell culture, alveolar or airway epithelial culture, stem cell-derived lung organoids or organoid-derived cells, microfabrication, polymer nanobiomaterials (including synthesis and physicochemical characterization), or microphysiological systems is highly desirable. Familiarity with pulmonary biomechanics, microfluidic instrumentation, polymeric drug delivery systems, immune cell profiling (e.g., RNA sequencing), and quantitative image analysis would be advantageous. The candidate should possess excellent experimental design, interdisciplinary collaboration, and scientific communication skills, and be capable of integrating tissue engineering, polymer biomaterials, and respiratory biomechanics to advance the development of predictive in vitro lung models for pulmonary surfactant evaluation. Proficiency in both written and spoken English is required. The Gilbreth Fellow will be expected to work independently in Purdue University laboratories under the guidance of the designated Co-Advisors.

Co-advisors

You-Yeon Won, Professor, Davidson School of Chemical Engineering, College of Engineering, Email: yywon@purdue.edu

Sunghee (Estelle) Park, Assistant Professor, Weldon School of Biomedical Engineering, College of Engineering, Email: park1713@purdue.edu 

Bibliography

Taesuk Jun, Daniel J. Fesenmeier, Sandra E. Torregrosa-Allen, Xinzhe Jin, Sangyoon Kim, Hye Jin Oh, Seon Yeop Jung, Bennett D. Elzey, Seyoung Kim, You-Yeon Won, “Intrapulmonary Spreading of Pharyngeally Instilled Liquids: Impact of Nanoparticle Concentration and PEG Lubrication in Polymer Lung Surfactant Solutions”, Molecular Pharmaceutics 22(10), 5975-5988, 2025 (DOI: 10.1021/acs.molpharmaceut.5c00629).

Daniel J. Fesenmeier, Madathilparambil V. Suresh, Seyoung Kim, Sungwan Park, Krishnan Raghavendran, You-Yeon Won, “Polymer Lung Surfactants Attenuate Direct Lung Injury in Mice”, ACS Biomaterials Science & Engineering 9(5), 2716-2730, 2023 (DOI: 10.1021/acsbiomaterials.3c00061).

Park, S.E., Kang, S., Paek, J. et al. Geometric engineering of organoid culture for enhanced organogenesis in a dish. Nat Methods 19, 1449–1460 (2022). https://doi.org/10.1038/s41592-022-01643-8

Sunghee Estelle Park et al. Organoids-on-a-chip.Science364,960-965(2019).DOI:10.1126/science.aaw7894

Jungwook Paek, Sunghee E. Park, Qiaozhi Lu, Kyu-Tae Park, Minseon Cho, Jeong Min Oh, Keon Woo Kwon, Yoon-suk Yi, Joseph W. Song, Hailey I. Edelstein, Jeff Ishibashi, Wenli Yang, Jacob W. Myerson, Raisa Y. Kiseleva, Pavel Aprelev, Elizabeth D. Hood, Dwight Stambolian, Patrick Seale, Vladimir R. Muzykantov, Dongeun Huh; Microphysiological Engineering of Self-Assembled and Perfusable Microvascular Beds for the Production of Vascularized Three-Dimensional Human Microtissues. ACS Nano 23 July 2019; 13 (7): 7627–7643. https://doi.org/10.1021/acsnano.9b00686