Researchers create a bioprinted microstructured ‘artificial lung’ model.
The COVID-19 pandemic has significantly affected our world, resulting in nearly 7.1 million deaths worldwide. In response, scientists and healthcare professionals have been tirelessly investigating the virus, its modes of transmission, and potential treatments. The pressing need for vaccines and effective therapies has led to increased calls for Korea to ramp up its drug development processes to align with those of more developed nations. Recently, a group of researchers in Korea has achieved a significant advancement aimed at improving the efficiency of respiratory disease research, which has garnered widespread attention.
The research team, led by Professor Sungjune Jung and PhD student Yunji Lee from the Department of Materials Science and Engineering at POSTECH, alongside Dr. Meehyein Kim and Dr. Myoung Kyu Lee from the Korea Research Institute of Chemical Technology’s Infectious Diseases Therapeutic Research Center (KRICT), has proudly developed artificial lungs. These innovative artificial lungs aim to facilitate the study of infections and the testing of medications for respiratory diseases, including COVID-19. Their groundbreaking findings have been published in the online edition of Biomaterials, a reputable journal focused on biomaterials research.
Typically, developing a new medication takes between 10 to 15 years and incurs costs exceeding 1 trillion won. This prolonged and costly endeavor is mainly due to current research strategies like 2D cell cultures and animal testing, which do not accurately replicate the in vivo (in the body) environment. To speed up development timelines and cut costs while improving success rates, it’s crucial to create models that closely resemble human biology.
In this innovative study, the researchers employed a “3D artificial lung” crafted through three-dimensional (3D) bioprinting technology. This cutting-edge technology leverages cells and biomaterials to generate realistic tissues and organs, significantly decreasing reliance on animal experiments in areas such as regenerative medicine and pharmaceutical development.
The newly developed “3D artificial lung” features three layers—vascular endothelium, extracellular matrix, and epithelium—similar to the structure of the human respiratory system. This model accurately mirrors the architecture and functions of the human lung, including critical aspects like cell-cell junctions and mucus production. Additionally, the model showcases high concentrations of proteins (ACE2 and TMPRSS2) that act as entry points for the COVID-19 virus at the epithelial layer, rendering it vulnerable to infection even when exposed to minimal viral doses. In contrast to traditional 2D cell culture models, which compromise cell integrity within five days of exposure, this artificial lung model remained functional for 21 days. This extended duration allowed researchers to observe cell damage due to infection and the degradation of barriers, enabling them to assess shifts in gene expression related to the infection pathway, viral replication, and the host immune response, aligning with real-life data observed in COVID-19 patients.
Furthermore, the team successfully modeled the mechanisms through which COVID-19 treatments (such as Remdesivir and Molnupiravir) reach the affected epithelial layer to inhibit viral replication. Unlike traditional 2D methods where medications are applied directly to epithelial cells, this study examined drug effectiveness after they maneuvered through the tissue barrier of the artificial lung. This method provided a true-to-life evaluation of the treatments’ efficacy, facilitated determination of the proper dosages, and helped identify possible side effects.
Professor Sungjune Jung from POSTECH emphasized, “Researchers have been warning that respiratory viruses akin to COVID-19 may emerge in the coming decade.” He further stated, “This research not only promises to significantly reduce the time required for drug development but also contributes to the formulation of therapeutic agents for COVID-19 and other respiratory illnesses.” Dr. Meehyein Kim from KRICT added, “To prepare for future pandemics like COVID-19, it’s crucial to improve early efficacy evaluation systems utilizing 3D cell and tissue culture technology that reflects clinical relevance. Moreover, promoting research in therapeutic development for human-affecting viruses using this technology is vital.”
This research was carried out with the backing of the Mid-Career Researcher Program from the National Research Foundation of Korea and the Korea Health Technology R&D Project from the Ministry of Health and Welfare.